We found two small studies that presented data for 49 participants with arterial leg ulcers (search conducted January 2019). The studies also included participants with other kinds of ulcers, and it is not clear what proportion of participants were diabetic. Neither study described the methods fully, both presented limited results for the arterial ulcer participants, and one study did not provide information on the number of participants with an arterial ulcer in the control group. The follow-up periods (six and eight weeks) were too short to measure healing. Therefore, the data that were available were incomplete and cannot be generalised to the greater population of people who suffer from arterial leg ulcers. One study randomised participants to either 2% ketanserin ointment in polyethylene glycol (PEG) or PEG alone, administered twice a day over eight weeks. This study reported increased wound healing in the ketanserin group, when compared with the control group. It should be noted that ketanserin is not licensed for use in humans in all countries. The second study randomised participants to either topically-applied growth factors isolated from the participant's own blood (concentrated growth factors (CGF)), or standard dressing; both applied weekly for six weeks. This study reported that 66.6% of CGF-treated diabetic arterial ulcers showed more than a 50% decrease in ulcer size, compared to 6.7% of non-healing ulcers treated with standard dressing. Only one study mentioned side effects, and reported that no participant experienced side effects during follow-up (six weeks). Neither of the two studies reported time to ulcer healing, patient satisfaction or quality of life measures. There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers. We downgraded the overall certainty of the available evidence to 'very low' and 'low', because the studies reported their methods poorly, there were only two studies and few participants with arterial disease, and because the studies were short and reported few results. This made it impossible to determine whether there was any real difference in the number of ulcers healed between the groups.
The searches are up-to-date to 26 January 2016. We found only one randomized trial that assessed the effect of the timing of surgery. It included a total of 40 participants, ranging in age from 47 to 84 years. From the limited evidence available, we cannot tell if the timing of surgery is an important factor in determining the outcome for individuals with recent symptoms from carotid artery narrowing. There is not enough evidence on the best time for surgical treatment for people with recent symptoms from carotid artery narrowing. The overall quality of the evidence was very low, due to the small number of participants from only one trial and missing outcome data. Further studies with a larger number of patients are needed.
The benefits of PN are uncertain as the evidence is of very low certainty, provided mainly by studies that only looked at people who received PN rather than comparing patients who received PN with those who did not. As we found no randomised controlled trials, we have included the results from 13 observational studies with a total of 721 participants. For 12 of the studies, there was only one relevant treatment group and no control group. Therefore, the results are only for people receiving PN and we have no information about those not receiving it. The average survival time for people on PN varied from three to 1278 days. Only three studies measured quality of life using a recognised measure. One study found quality of life improved and two studies found similar numbers of people both improved and deteriorated. However, the three studies monitored quality of life at different points in time and measured it in different ways. Side effects occurred in 12% of people in the eight studies that measured them. Further research is needed to find out if PN is of benefit to people with an inoperable blockage of the bowel caused by advanced cancer.
The findings of this review were inconclusive for a number of reasons. First, because the included trials measured different outcomes in different ways, we were unable to combine their results. Second, these trials presented the written information for patients in different ways, and most did not design the leaflets in a way that made them easy to read. Third, in many cases trials were not clearly reported, so we do not know if they were carried out correctly. Despite these limitations several trials, while using different types of information and different measures, found written information improved knowledge. This is encouraging for people who want to learn about their medicines from leaflets. None of the studies showed that written information was harmful. Future research needs to use improved methods, and needs to examine the same measures on many occasions. It is important that medicines information be well written and designed to maximise the possibility of improving knowledge. Consumers are increasingly seeking out health information, including information about medicines, on the internet, but we found no trials examining whether internet-based medicines information changed people's knowledge, attitudes, or behaviour.
We searched published medical articles to find research papers that looked at combined treatment strategies with surgery for treating people with primary pleural cancer. We looked for randomised clinical trials (where people were allocated at random to one of two or more treatments groups) and used information from those we found to form our conclusions. We found evidence up to 21 March 2017. The review authors found two small randomised clinical trials, in which a total of 104 people with pleural mesothelioma were randomised. One trial compared the addition of surgery and radiotherapy to chemotherapy with chemotherapy alone. The other trial compared the addition of radiotherapy to chemotherapy and surgery with chemotherapy and surgery alone. These two small trials suggested that there is no added value for either radiotherapy or combined radiotherapy and surgery. We could not combine the data from the trials as we had intended, because the two trials were too different. We rated the quality of evidence as moderate for survival and low quality for all the other outcomes studied. The review authors identified three ongoing randomised clinical trials, the results of which have not been published yet. We only found two relevant trials. Both were small, which made the results uncertain. It is not clear whether giving a combination of surgery and radical radiotherapy after chemotherapy is better than giving chemotherapy alone. Radical radiotherapy does not seem to improve the results of surgery alone.
This review included two randomized controlled trials (involving 5455 women). Data could not be combined because each trial measured effectiveness in different ways. One study was from Canada and involved 432 women randomly assigned to a 10-minute presentation during a prenatal class about toxoplasmosis prevention or to a usual prenatal class. Losses to follow-up were high and 285 completed the post-test questionnaire in the third trimester. Only 5% of the intervention women recalled having obtained information on toxoplasmosis prevention during prenatal classes. However, the authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The other trial conducted in France involved 5023 pregnant women with no evidence of toxoplasmosis infection (seronegative) who were randomly assigned to receive a brochure and an audiotape containing information for toxoplasmosis prevention, or to a usual prenatal class. Losses to follow-up were high and 2790 completed both pre-test and post-test questionnaire on behavior (44.5% loss to follow-up), whereas 3949 women were tested for blood antibodies (22.4% loss to follow-up). Women's behavior did not change after the intervention. Similarly, the seroconversion rate did not differ between groups (13 out of 2591 women seroconverted in the intervention and four out of 1358 in the control group). Both trials were judged as having low methodological quality as assessed by the GRADE approach. This limits our confidence in the results. Evidence supporting prenatal education to prevent congenital toxoplasmosis is therefore limited.
Among the pertinent medical literature only  two studies, comprising  a total of 123 participants,  met the criteria of the methodological quality necessary for their inclusion in this review. Taking into account  the disability progression, the analysis of the data showed that INF beta treatment in  patients with PPMS was  not associated with a reduction of  this parameter during the first two years of therapy. Adverse effects, mainly flu-like symptoms and injection site reactions, occurred frequently and were the same as  reported by the many studies on   IFN beta treatments in MS patients with different types of the disease. It is worth nothing that the patients’ population analysed was too small to allow a definitive conclusion on the efficacy of IFN beta therapy  in PPMS.
Evidence in this review is current to July 2019. We included two randomised controlled trials (where participants have an equal chance of being assigned to either treatment) including 1674 adult participants who had one or more risk factors for developing CVD, which compared NP-guided treatment with standard care. We excluded patients with symptoms of heart failure. The mean age of participants varied between 64.1 and 67.8 years. Patients were followed-up for between 2 years and a mean of 4.2 years. Effects of NP-guided treatment on death due to CVD or for any other reason remain uncertain as our results were imprecise. Moderate-quality evidence suggests that NP-guided treatment probably reduces the number of hospitalisations due to cardiovascular events and due to all causes in patients with cardiovascular risk factors. We would expect that of 1000 patients who received standard care, 163 would be admitted to hospital as the result of a cardiovascular event, compared to between 65 and 111 patients who received NP-guided treatment. Out of 1000 patients with cardiovascular risk factors who received standard care, 601 would be admitted to hospital for any reason, compared to between 457 and 553 patients who received NP-guided treatment. High-quality evidence indicates that NP-guided treatment reduces the risk of ventricular dysfunction (a condition that often leads to heart failure) compared to standard care. Our results suggest that of 1000 patients with cardiovascular risk factors who received standard care, 87 would develop ventricular dysfunction, compared to between 36 and 79 patients who received NP-guided treatment. No evidence suggests that NP-guided treatment affected NP level at completion of the studies. The quality of evidence ranged from low to high across outcomes. Key reasons for concern about the quality of the evidence included risk of bias, as patients and medical staff caring for patients knew whether they were in the control or intervention group and this may have affected the care they received; some results obtained were imprecise, and it is unclear if the intervention was beneficial or harmful. As we identified only two studies that were suitable for inclusion in this review, the generalisability of the review is limited.
Three randomised controlled trials involving a total of 404, mainly female and older, people with displaced fractures of the distal radius are included in this review. None of the trials assessed functional outcome, and only one trial reported on complications. Each trial compared different methods of reduction. One trial, in which all participants had intravenous regional anaesthesia, found no significant differences in anatomical outcomes between mechanical reduction using finger trap traction and manual reduction. The second trial compared two methods of manual reduction. These were a novel method of manual reduction where participants actively provided counter-traction without being given anaesthesia versus traditional manual reduction under intravenous regional anaesthesia. The participants of the novel method group suffered more but not intolerable pain during the reduction procedure, which was shorter in duration. No differences in anatomical outcome were detected. The third trial compared mechanical reduction involving a special device without anaesthesia versus manual reduction under haematoma block (local anaesthesia). Less pain during the reduction procedure was recorded for the mechanical traction group. Both methods yielded similar anatomical results. Fewer participants of the mechanical traction group had signs of neurological impairment, mainly finger numbness, at five weeks but this difference was not statistically significant by one year. The review concluded that there was not enough evidence to decide whether there was any difference between the various methods tested.
This review of 22 trials involving 673 women and seven different adrenergic drugs found weak evidence that adrenergic agonists may help stress urinary incontinence. Side effects do occur but are usually minor. Rarely, more serious adverse effects such as high blood pressure can occur. More evidence is needed to compare adrenergic drugs with other drugs for stress incontinence and also with pelvic floor muscle exercises.
We found six studies, all from the USA, four of which targeted African Americans and two which targeted Latino or Chinese immigrants. Of the studies, four were experimental (1693 volunteers) and two reported the results of large, targeted campaigns run in whole communities and cities. The evidence is current to August 2016. The available evidence is insufficient to conclude whether targeted mass media interventions for ethnic minority groups are more, less or equally effective in changing health behaviours than general mass media interventions. Only one study compared participants' smoking habits and intentions to quit following the receipt of either a culturally adapted smoking advice booklet or a booklet developed for the general population. They found little or no differences in smoking behaviours between the groups. When compared to no mass media intervention, a targeted mass media intervention may increase the number of calls to smoking quit lines, but the effect on health behaviours is unclear. This conclusion is based on findings from three studies. One study gave participants access to a series of 12 live shows on cable TV with information on how to maintain a healthy weight through diet and physical activity. Compared to women who did not watch the shows, participants reported slightly increased physical activity and some positive changes to their dietary patterns; however, their body weight was no different over time. Two other studies were large-scale targeted campaigns in which smokers were encouraged to call a quit line for smoking cessation advice. The number of telephone calls from the target population increased considerably during the campaign. This review also compared targeted mass media interventions versus mass media interventions with added personal interactions. These findings, based on three studies, were inconclusive. None of the studies reported whether the interventions could have had any adverse effects, such as possible stigmatisation or increased resistance to messages. Further studies directly comparing targeted mass media interventions with general mass media interventions would be useful. Few studies have investigated the effects of targeted mass media interventions for ethnic minority groups who primarily speak a non-dominant language. Our confidence in the evidence of effect on all main outcomes is low to very low. This means that the true effect may be different or substantially different from the results presented in this review. We have moderate confidence in the estimated increase in the number of calls to smoking quit lines.
We included 14 controlled trials involving 805 critically ill participants on mechanical ventilation. All participants were alert. Slightly more patients (58%) included in these studies were male and their average age was 58 years. The majority of the studies examined the effects of patients listening to pre-recorded music. Most studies offered one 20 to 30-minute music session to the participants. The findings suggest that music listening may have a large anxiety-reducing effect on mechanically ventilated patients. The results furthermore suggest that music listening consistently reduces respiratory rate and systolic blood pressure, suggesting a relaxation response. No evidence of effect was found for diastolic blood pressure, mean arterial pressure, or oxygen saturation level and inconsistent results were found for heart rate and hormone levels. One large-scale study reported greater reductions in the intake of sedative and analgesic medications in the music listening group compared to the control group, and two other studies reported similar trends. Music listening did not result in any harm. Most trials presented some methodological weakness. Therefore, these results need to be interpreted with caution. However, the results are consistent with the findings of three other Cochrane systematic reviews on the use of music interventions for anxiety reduction in medical patients. Therefore, we conclude that music interventions may provide a viable anxiety management option to mechanically ventilated patients.
We searched electronic databases and the Chinese Clinical Trial Registry up to February 2017, and two clinical trials platforms (WHO International Clinical Trials Registry Platform and Clinicaltrials.gov) up to April 2017. We included in this review 33 randomized clinical trials (RCTs) with 3946 participants. Of these, results were available for up to 22 trials (2865 participants) that compared acupuncture with any control but for only six trials (668 participants) that compared acupuncture with a sham acupuncture procedure. The effects of acupuncture in reducing death or dependency or improving neurological and movement scores at the end of follow-up, as seen in trials comparing acupuncture with any control, were not seen in trials comparing acupuncture with the more reliable control of sham acupuncture. Adverse events such as pain, dizziness, and faint were reported in 6.2% (64/1037) of participants, and 1.4% (14) of these had to discontinue acupuncture. The quality of the evidence was low or very low owing to risk of bias in the included studies and variation in the type and duration of acupuncture. Additional larger reliable research trials are required for enhanced confidence in the effects of acupuncture for acute stroke.
This review included 16 randomised controlled trials involving 2091 women at high risk of OHSS, which evaluated three different dopamine agonists (cabergoline, bromocriptine and quinagolide). The main outcome measures were the number of new cases (incidence) of moderate or severe OHSS and live birth rate. The evidence is current to August 2016. Dopamine agonists appear to reduce the incidence of moderate or severe OHSS in women at high risk of OHSS (moderate quality evidence) compared with placebo or no treatment. This suggests that if 29% of women taking placebo or no treatment have moderate or severe OHSS, between 7% and 14% of women taking dopamine agonists will have moderate or severe OHSS. For women who had a fresh embryo transferred as part of their treatment cycle, there was no evidence that dopamine agonists influenced pregnancy outcomes, but they might increase the risk of side effects, such as stomach upsets. There was no evidence of a difference between a dopamine agonist plus another active treatment versus another active treatment on incidence of moderate or severe OHSS and live birth rate. There was no evidence of a difference in OHSS rates between cabergoline and placebo treatments (e.g. hydroxyethyl starch, prednisolone or 'coasting' (withholding any more ovarian stimulation for a few days)). Cabergoline was associated with an increased clinical pregnancy rate compared with coasting. The quality of the evidence ranged from very low to moderate. Limitations included poor reporting of study methods and imprecision (too few events) for some comparisons.
Through September 2013, we did computer searches for studies of programs to improve condom use. We wrote to researchers for missing data. The studies could have various designs. The education program addressed preventing pregnancy and HIV/STI. The intervention was compared with a different program, usual care, or no intervention. The studies had a clinical outcome such as pregnancy, HIV, or STI tests. We did not use self-reports of condom use. We found seven randomized trials. Six assigned groups (clusters) and one randomized individuals. Four trials took place in African countries, two in the USA, and one in England. The studies were based in schools, community settings, a clinic, and a military training setting. Five trials examined pregnancy, four studied HIV and HSV-2 (herpes), and three assessed other STI. We found no major differences between study groups for pregnancy or HIV. Some results were seen for STI outcomes. Two studies showed fewer HSV-2 cases with the behavioral program compared to the control group. One also reported fewer cases of syphilis and gonorrhea with the behavioral program plus STI management. Another study reported a higher gonorrhea rate for the intervention group. The researchers believed the result was due to a subgroup that did not have the full program. We found little clinical effect of improving condom use. The studies provided moderate to low quality information. Losses to follow up were high. We need good programs on condom use to prevent pregnancy and HIV/STI. Programs should be useful for settings with few resources. Interventions should be tested with valid outcome measures.
Electrostimulation is a potential treatment to improve recovery of movement control and functional ability after stroke but the results of this review are inconclusive. After stroke many people are unable to use their affected limbs in everyday activities such as walking, ascending/descending stairs, washing hair or opening a coffee jar. One way to improve recovery might be to train affected muscles by using electrostimulation. This review examined the findings of 24 randomised controlled trials of electrostimulation provided to improve the ability to voluntarily move the affected limb and/or use the affected limb in everyday activities. The available evidence suggests that when electrostimulation is compared to no treatment then there might be a small effect on some aspects of function in favour of electrostimulation. However, the majority of findings in favour of electrostimulation were found when it was compared to a group of stroke patients who were not receiving any treatment and for all but two of the outcomes examined there were no differences between either electrostimulation and placebo or between electrostimulation and another type of physical therapy. This review also found that there were many differences between randomised controlled trials in the types of stroke patients who were included, the doses of electrostimulation and the outcome measures used. This meant that many of the comparisons made in the review related to one randomised trial rather than two or more. In addition, the numbers of participants in trials were relatively small. The results of this review therefore need to be interpreted with caution.
Infliximab is a relatively new disease modifying anti-rheumatic drug that inhibits tumour necrosis factor alpha. Short term (six to twelve month) studies suggest infliximab is well tolerated, and in combination with methotrexate, decreases disease activity in RA. Infliximab 3mg/kg or 10mg/kg, in combination with methotrexate, taken every 4 or 8 weeks for either 6 or 12 months, significantly improved disease activity as measured by tender and swollen joints and ACR response rates. Pain and physical function also improved compared to those taking methotrexate alone. Infliximab significantly reduced radiographic progression at 12 months.
Our review of studies conducted over the past 14 years suggests that azithromycin is a relatively weak antimalarial whose efficacy depends on the drug dose and the partner drug in the combination therapy. The data suggest that, among adults, the higher doses needed to achieve an acceptable level of treatment success with malaria may be less well tolerated. Unless the ongoing product and dose optimisation process results in a universally efficacious product or identifies a specific niche application that is complementary to the current scala of more efficacious antimalarial combinations, azithromycin's future as an antimalarial does not look promising.
We conducted thorough searches for randomised controlled trials (RCTs), quasi-randomised controlled trials (q-RCTs), controlled before-and-after studies (CBAs); and interrupted time series (ITS) studies of interventions to increase shared decision making in people with mental health conditions. We found two studies that met the inclusion criteria. Both studies were of good quality and made attempts to reduce potential sources of bias. We examined whether interventions to increase shared decision making affected patient satisfaction with treatment or care, led to better health outcomes or to patients being less likely to be readmitted to hospital. One of the studies indicated that the intervention increased patient satisfaction in the short term. One study indicated that doctor facilitation of consumer involvement in decision making was increased by the intervention, but no effects were found on the clinical or health service outcomes in either study. Neither study reported that shared decision making for people with mental health conditions is harmful. However, no firm conclusions can be drawn from these two studies on any of the outcomes measured and further research is needed.
Authors search medical databases and identified 19 randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) with 759 women that could be included in the review, but data from only nine trials were suitable for analyses. Women sought help for HMB when it affected their quality of life. Levels of prostaglandin (a naturally occurring hormone) are higher in women with HMB and are reduced by NSAIDs. The review of trials found that NSAIDs were modestly effective in reducing HMB, but other medicines, such as danazol, tranexamic acid and levonorgestrel-releasing intrauterine system (LNG IUS), are more effective. These results were based on a small number of low- to moderate-quality trials. The evidence quality ranged from low to moderate, the main limitations being poor reporting of study methods and imprecision resulting from small study numbers.
In October 2015, we searched the medical literature and found 23 studies involving 8079 participants looking at paracetamol for frequent episodic tension-type headache. About 6000 participants were involved in comparisons between paracetamol 1000 mg and placebo (a dummy tablet). Results were usually reported two hours after taking the medicine or placebo. The International Headache Society recommends the outcome of being pain free two hours after taking a medicine, but other outcomes are also suggested. Few studies reported pain free at two hours or other outcomes, so there was limited information to analyse for some outcomes. The outcome of being pain free at two hours was reported by 24 in 100 people taking paracetamol 1000 mg, and in 19 out of 100 people taking placebo, meaning that only 5 in 100 people benefited because of paracetamol 1000 mg (high quality evidence). The outcome of being pain free or having only mild pain at two hours was reported by 59 in 100 people taking paracetamol 1000 mg, and in 49 out of 100 people taking placebo (high quality evidence), meaning that only 10 in 100 people benefited because of paracetamol 1000 mg. About 10 in 100 people taking paracetamol 1000 mg reported having a side effect, which was the same as with placebo (9 in 100 people) (high quality evidence). Most side effects were mild or moderate in intensity. No side effects were serious. We found a very small amount of information comparing paracetamol 500 mg or 650 mg with placebo, and comparing paracetamol 1000 mg with other painkillers. There was no difference between any of these treatments. The quality of the evidence was moderate or high for paracetamol 1000 mg compared with placebo, and low or very low for paracetamol 500 mg to 650 mg compared with placebo, and for paracetamol 1000 mg compared with other painkillers. High quality evidence means that we are very certain about the results. Low quality evidence means that we are very uncertain about the results.
The Information Specialist of Cochrane Schizophrenia ran an electronic search of their specialised register up to 30 March 2017 for trials that randomised people with schizophrenia who were not responding to their initial antipsychotic treatment to receive either an increased antipsychotic dose or continue on the same dose. The search returned 1919 records, which were checked for eligibility by the review authors. Ten trials met the review requirements and provided usable data. No clear difference between increasing the dose of the antipsychotic drug and continuing antipsychotic treatment at the same dose was shown for any efficacy (clinical response) or safety (incidence of adverse effects) outcomes. The evidence currently available is limited and of low or very low quality. In particular, very few studies reported adverse effects adequately. The results of the present review show that there is no good-quality evidence to support or refute the hypothesis that increasing the antipsychotic dose for patients not responding to their initial antipsychotic treatment differs from continuing antipsychotic treatment at the same dose. No clear evidence regarding safety is available. Therefore, no firm conclusions can be made. Larger, well-designed trials are needed.
The review included 13 studies with 512 adults and children with cystic fibrosis; in all of them treatment lasted for four weeks. Studies compared different formulations of pancreatic enzyme supplements, so we could not combine many of the results. Also the design of 12 of the studies meant that those taking part received both types of supplement for four weeks each, although the order in which they received them was chosen at random. This also made it difficult to analyse the results. Most of the studies were old; the most recent was from 2015, but the oldest was from 1986. We could only combine data from two small studies where individuals took miniature drug capsules (microspheres), which were treated so that the release of the medication is delayed until they have passed from the stomach into the intestine, and normal size tablets which were treated in the same way. The results did not clearly favour one or the other treatment for any of our most important outcomes (weight, height or body mass index). However, those taking the delayed-release microspheres had less fat in their feces than those taking delayed release tablets (normal size) as well as having less abdominal pain and not needing to go to the toilet as often. In a different study, those people taking the delayed-release microspheres also had less fat in their feces than those taking supplements that weren't treated so the release of medication was delayed. We didn't find any evidence that one type of these enteric-coated microspheres was better than another; or that enteric-coated microspheres were better than enteric-coated mini-microspheres (which are smaller). We didn't find any evidence on different doses of enzymes needed for people who produce different levels of pancreatic enzymes, on the best time for individuals to start treatment and different amounts of supplements based on differences in type of food eaten and meal sizes. A properly designed sudy is needed to answer these questions. We could not be sure that the people in the included studies had equal chances of being put into the different treatment groups as no details were published about how the decisions were made. Several studies also had large numbers of individuals who dropped out and often reasons for this were not given. In most studies, people took one treatment and then after a while swapped to the alternative treatment; we could only combine results from two studies which were designed in this way, and that design means that the results may seem to be more consistent than they really are when we analyse them. Finally, several studies did not completely report their findings in a way we could analyse in this review. We are not sure how these factors affect our confidence in the results we found.
We found five trials which included a total of 167 people. The trials showed that adding G-CSF to usual therapy did not significantly affect the likelihood of the infection resolving or the improved healing of foot wounds, nor did it reduce the period of treatment with oral antibiotics. However, G-CSF does appear to reduce the need for surgical interventions, especially amputations, and the number of days spent in hospital. There are limitations to this analysis related to the variations in the people included in the studies (e.g. the severity of infection, the timing of the clinical assessment, the use of different G-CSF preparations, and for different lengths of time). Therefore caution is required in the interpretation of the findings.
The aim of this review was to assess effectiveness of the telephone for HIV test result delivery, compared with face-to-face or other methods of HIV test result notification. After a comprehensive search of various scientific databases and other resources, we found only one relevant study. This study was performed in 1998-1999 in the United States on high-risk and homeless youth. The participants were offered an HIV test and told that their HIV test results would be available in two weeks. They were then divided into two groups; one that had to return to the testing site to get their HIV test results, and another that had the option of receiving HIV test results either by telephone or face-to-face at the testing site. Overall, less than half of participants received their HIV test results. Most participants in the telephone notification group opted for telephone rather than in person delivery of HIV test results.The proportion of youth receiving their HIV test results in the telephone group was significantly higher compared to the face-to-face group. However, since none of the participants in the telephone group were HIV positive, the study could not provide information about the effectiveness of telephone HIV test result delivery in people with HIV. In addition, we could not find any information about other relevant outcomes such as participants’ and providers’ satisfaction with the telephone HIV test results delivery, cost or potential harmful effects of this intervention. We urgently need more studies conducted in various settings comparing the effectiveness of telephone to other ways of HIV test result delivery and providing other relevant information in addition to the proportion of people receiving their HIV test results.
We found 14 studies comparing hypnotherapy with other approaches to help people stop smoking (including brief advice, or more intensive stop-smoking counselling), or no treatment. Overall, 1926 people were included. Studies lasted at least six months. The studies varied greatly in terms of the treatments they compared, so it was difficult to combine their results. We searched for evidence up to 18 July 2018. When we combined the results of six studies (with a total of 957 people) there was no evidence that hypnotherapy helped people quit smoking more than behavioural interventions, such as counselling, when delivered over the same amount of time. There was also no evidence that there was a difference between hypnotherapy and longer counselling programmes when we combined results from two studies (269 people). One study compared hypnotherapy with no treatment and found an effect in favour of hypnotherapy, but the study was small (40 people) and had issues with its methods, which means we cannot be certain about this finding. Most of the studies did not say if they also evaluated the safety of hypnotherapy. Five studies looked at adding hypnotherapy to existing treatments and found an effect, but the studies were at high risk of bias and there were large, unexplained differences in their findings. One study that compared hypnotherapy and relaxation found no difference in side effects. The evidence in this review ranges from low to very low certainty, as there was not enough information and many of the studies had issues with their designs. There is no clear evidence that hypnotherapy is better than other approaches in helping people to stop smoking. If a benefit is present, current evidence suggests the benefit is small at most. Larger, high-quality studies are needed.
The content of this review is current to September 2019. We included only studies where chance determined what treatment people in the study would get. We found 12 studies including 2932 people who matched our question. We found that BCG may lead to similar risk of dying from any cause over time (low-quality evidence), but may increase the risk of serious unwanted effects (low-quality evidence), although it is possible that it does not make a difference. BCG may reduce the risk that the tumour comes back over time (low-quality evidence), although it is possible that it does not make a difference. BCG may have little or no effect on the risk that the tumour gets worse over time (low-quality evidence). We found no data on quality of life. The quality of the evidence was consistently rated as low, meaning that our confidence is limited, and future research may change these findings.
This updated review evaluated the effectiveness of various rehabilitation programmes for patients who had lumbar disc surgery for the first time. We included 22 randomised controlled trials with 2503 participants, both men and women, between the ages of 18 and 65 years. The evidence is current to May 2013. Most commonly, treatment started four to six weeks after surgery, but the start of treatment ranged from two hours to 12 months after surgery. Considerable variation in the content, duration and intensity of treatments (i.e. exercise programmes) has been noted. The duration of the interventions varied from two weeks to one year; most programmes lasted six to 12 weeks. Participants reported on average serious pain intensity (56 points on a zero to 100 scale, with 100 being the worst possible pain). Most studies compared (1) exercise versus no treatment, (2) high-intensity exercise versus low-intensity exercise or (3) supervised exercise versus home exercise, most commonly starting four to six weeks after surgery. Comparisons in this review included (1) exercise versus no treatment, (2) high-intensity versus low-intensity exercise and (3) supervised versus home exercise. Patients who participated in exercise programmes four to six weeks after surgery reported slightly less short-term pain and disability than those who received no treatment. Patients who participated in high-intensity exercise programmes reported slightly less short-term pain and disability than those participating in low-intensity exercise programmes. Patients in supervised exercise programmes reported little or no difference in pain and disability compared with those in home exercise programmes. Here it was difficult to draw firm conclusions in the absence of high-quality evidence. None of the trials reported an increase in reoperation rate after first-time lumbar surgery. The evidence does not show whether all patients should be treated after surgery or only those who still have symptoms four to six weeks later. Limitations in the methods of half of the trials suggest that the results should be read with caution. Most of the treatments were assessed in only one trial. Therefore for most of the interventions, only low- to very low-quality evidence indicates that no firm conclusions can be drawn regarding their effectiveness.
We found 23 studies including 39,195 participants that compared niacin to placebo. The evidence is current up to August 2016. The majority of included participants were on average 65 years old and had already experienced a myocardial infarction. The participants took niacin or placebo for a period of between six months and five years. Seventeen out of 23 studies were fully or partially funded by the drug manufacturer with a commercial interest in the results of the studies. Niacin did not reduce the number of deaths, heart attack or stroke. Many people (18%) had to stop taking niacin due to side effects. The results did not differ between participants who had or had not experienced a heart attack before taking niacin. The results did not differ between participants who were or were not taking a statin (another drug that prevents heart attack and stroke). The overall quality of evidence was moderate to high. In summary, we found no evidence of benefits from niacin therapy.
This review aimed to determine the benefit and harms of the use of routine stenting in kidney transplant recipients in the prevention of urological complications. Seven studies (1154 patients) were identified. The incidence of MUCs were significantly reduced by the use of prophylactic stenting. Urinary tract infections (UTIs) were more common in stented patients however the addition of antibiotic prophylaxis resulted in no difference in the incidence of UTIs between the two groups. More studies are needed to investigate the use of selective versus universal prophylactic stenting for the unresolved issues of quality of life and cost.
Only one randomised trial has assessed the effectiveness of a non-drug treatment for lower limb muscle cramp. This trial evaluated day-time calf muscle stretching to prevent nighttime muscle cramp in adults age 60 years and over who had received a repeat prescription of quinine for nighttime cramps in the preceding three months. Forty-nine participants were advised to complete lean-to-wall calf muscle stretching held for 10 s three times per day. Forty-eight participants were allocated to a placebo stretching group. After 12 weeks, there was no statistically significant difference in the frequency of cramps, as recalled by the participants, between groups. No "significant" adverse effect was reported. Owing to serious limitations in the design of the trial, it is impossible to determine from the available evidence whether or not calf muscle stretching can prevent recurrent lower limb muscle cramp. Further research is required to determine the effectiveness of non-drug treatments for lower limb muscle cramp.
The evidence is current to May 2015. We found 12 relevant studies (with 2351 participants) comparing colloids with crystalloids. Eleven of these studies included people with ischaemic stroke (stroke sustained due to a clot), whilst one study included people with haemorrhagic stroke (stroke due to a bleed). Five of these studies (1420 participants) also made a comparison between 0.9% saline, the most commonly prescribed iv fluid, and another fluid type. The largest study had 841 participants, whilst the smallest had 27 participants. The length of time that fluids were given varied between trials, from two hours to 10 days. Ten studies revealed a source of funding. Of these, two studies were funded by fluid manufacturers. We did not find any studies that examined the best fluid volume, mode of fluid delivery, or duration of fluid treatment. We found that people with acute stroke given crystalloids (including 0.9% saline) had about the same risk of death or dependence as people given other fluid types. People given crystalloids also had a lower risk of pulmonary oedema, a complication that can lead to breathlessness due to excess collection of watery fluid in the lungs. From the evidence we obtained, it was difficult to make any concrete conclusions about which fluids were better for reducing brain swelling (cerebral oedema) or a serious lung infection (pneumonia). We found no evidence to guide the best volume, duration, or mode of parenteral fluid delivery for people with acute stroke. The majority of studies had a low to moderate risk of bias based on study limitations and inconsistency. Most studies reported the outcomes they stated they would.
Three trials involving 5905 participants were included. We found very little evidence in relation to the use of formoterol and budesonide for relief of symptoms in people with mild asthma, but in people with more severe asthma who had suffered exacerbations in spite of regular treatment with inhaled corticosteroids, we found that reliever formoterol and budesonide compared favourably with terbutaline in reducing asthma exacerbations that required a course of oral corticosteroids. However only a small proportion of the 'severe asthma exacerbations' as defined in the trials led to hospital admissions, and no significant overall benefit has yet been shown for this outcome. In children with asthma that was not controlled with regular inhaled corticosteroids, there were fewer serious adverse events when formoterol and budesonide were used to relieve symptoms as well as for maintenance treatment.
Lumiracoxib 400 mg provided rapid, effective, and sustained relief of postoperative pain in four studies in dental and orthopaedic surgery. Of 366 participants treated with lumiracoxib 400 mg half experienced a high level of pain relief (at least 50% pain relief over a six hour period), compared with 8% given placebo. The duration of analgesia was relatively long at 9 hours, and fewer participants needed to use rescue medication with lumiracoxib than with placebo. Adverse event data was inconsistently reported, but no serious adverse events occurred in any patient taking lumiracoxib in these studies.
Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 23 January 2018. We searched scientific databases for clinical trials in children or adults treated with slow-release fluoride devices compared with another type of fluoride treatment (e.g. toothpaste, mouthrinse, gel, or varnish), placebo (a pretend treatment), or no treatment (usual care). Treatments had to be used and monitored for a minimum of 1 year. We found one study that randomised 174 children to either slow-dissolving, fluoride-releasing glass beads or placebo beads. The setting was an inner city school in an area served with low-fluoride water. Only 48% of children retained the beads and were available for analysis. There is insufficient evidence to determine whether slow-release fluoride devices (such as glass beads) help reduce dental decay. Retention of the beads is a problem. The evidence relating caries increment, side effects and retention was considered to be very low quality.
Six randomised controlled trials (RCTs) were reviewed with a total of 361 participants consisting of adults with any type of glaucoma and follow-up of at least 24 months. We last searched the databases on 23 October 2015. Failure rate at 24 months was not reported in any included studies, and one study reported "late complications" but did not specify a time period, which favoured the fornix-based treatment. No difference was noted with respect to lowering eye pressure after 24 months (two trials) and after 12 months (four trials). The number of medications needed to control eye pressure after surgery was also similar. Moreover, most of the studies reported that the complication rates after the operation were similar except in one complication which was narrowing in the anterior part of the eye after the procedure (more common in the limbal surgery group), but this did not affect the final outcome of the surgery. Although all six trials were reported to be randomised, the procedures followed for randomisation were mostly unclear (four of the six studies). Masking of the outcomes was not clear or not addressed in all six trials. Missing information was encountered in only one trial which also suffered from bias in reporting its outcomes. All other trials had an unclear risk of reporting bias as there was no access to original data.
Our evidence is current to August 2015. We did not identify any new trials for the update of this review. The previous publication of this review included seven trials with 362 participants. Four trials compared the effect of a steroid to a placebo, one to aspirin, and two trials explored the effects of steroids in conjunction with an antiviral. The length of treatment varied between a single dose and a 12-day course. The doses used also varied. The length of follow-up varied from short periods (i.e. days or weeks) to longer periods (i.e. six months and 12 months). Steroid treatment relieved sore throat in the short term (at 12 hours). The researchers noticed a benefit at two to four days when steroids were used in combination with an antiviral medication, but these findings are limited since researchers assessed them in one or two trials only. The findings on the effect of steroids alone or when used with an antiviral medication for other symptoms were less clear. We are unsure about adverse effects from using steroids. With the exception of two trials, most studies did not set out a prior plan to evaluate the occurrence of side effects, or other adverse events. None of the trials explored adverse effects in the longer term (over years). The quality of the included trials was generally poor. We cannot know the exact effect of using steroids for glandular fever.
We considered twenty four studies for inclusion in this review. This review identified twenty randomised controlled trials enrolling a total of (2334) participants which compared an intervention using phlebotonics with a control intervention. Of these twenty studies, one study compared phlebotonics with a medical intervention and another with rubber band ligation. Of the remaining four trials, we identified two trials which compared phlebotonics with each other, one trial which compared phlebotonics with herbal therapy and one trial which compared phlebotonics with infrared photocoagulation. The trials obtained did not show any significant adverse events or side-effects from the use of phlebotonics. The studies demonstrated a beneficial effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease as well as symptom relief post-haemorrhoidectomy.
We included seven randomised controlled trials involving 239 participants in the review, which reported on the use of antidepressants for treating emotionalism. Trials ranged from small (10 participants) to large (92 participants). Mean/median age of participants ranged from 57.8 years to 73 years. Studies were from Europe (UK: 1, Denmark: 1, Scotland: 1, and Sweden: 1); Asia (South Korea: 1; and Japan: 1); and the USA: 1. We included seven trials involving 239 participants (we identified no new trials since the previous version of the review). Two trials were of cross-over design, and outcome data were not available from the first phase (precross-over) in an appropriate format for inclusion as a parallel randomised controlled trial (RCT). Data were only available for five trials with 213 participants. We observed treatment effects on the following: 50% reduction in emotionalism, improvements (reduction) in lability, Clinician Interview-Based Impression of Change (CIBIC), diminished tearfulness and scores on the Pathological Laughter and Crying Scale (PLCS). However, confidence intervals were wide indicating that treatment may have had only a small positive effect, or even a small negative effect (in one trial). Six trials reported death as an adverse event and found no differences between groups. We rated the evidence from very low to moderate quality due to these being small trials with some degree of bias. Antidepressant drugs appear to reduce outbursts of crying or laughing. More trials with systematic assessment and reporting of adverse events are needed to ensure that these benefits outweigh the risks.
This review asks whether there is evidence that its use during the initial stages of surgery to prevent the excessive conjunctival scarring reduces the risk of failure of the operation. Three types of patient were included: those at high risk of failure because of previous failed surgery or other complications, those having combined cataract and glaucoma surgery and those having primary trabeculectomy - an operation for the first time for their glaucoma. The review found evidence that Mitomycin C reduces the risk of surgical failure in both high risk and primary surgery but no evidence on combined cataract and glaucoma surgery. But the risk of adverse effects including an increased risk of cataracts (not in the combined group) was also noted. There were only a few studies on each category of patients and most were of only poor or moderate quality.
One study randomly assigned 166 preterm infants and reported data on 144 infants. The included study was completed before the introduction of surfactant and widespread use of antenatal steroids. This trial demonstrated no differences in outcomes among infants who received high-frequency jet ventilation. In this trial, cross-over to the alternate treatment was permitted if initial treatment failed. Investigators found no statistically significant differences in overall mortality (including survival after cross-over) between the two groups. In a secondary analysis, researchers showed that rescue treatment with HFJV, up to the time of cross-over, was associated with lower mortality. Researchers reported no differences in the incidence of chronic lung disease among survivors at 28 days of age, and they found no differences in intraventricular haemorrhage, new air leaks, airway obstruction and necrotising tracheobronchitis. Existing evidence does not support the use of rescue high-frequency jet ventilation compared with conventional mechanical ventilation for treatment of preterm infants with severe pulmonary problems. Additional research is needed.
We included five trials which were all conducted in high-income countries. Our search is current up until 28 January 2019. One trial compared plasma transfusion with no transfusion given. Another trial compared plasma or platelet transfusion or both with neither plasma nor platelet transfusion given. One trial compared plasma transfusion with alternative products given to help blood clot. Another trial compared different blood tests to trigger a plasma transfusion, and still another trial compared different transfusion triggers using the same blood test. Four trials involved adult participants over 18 years old, and the fifth trial did not specify age of participants. In four trials, participants underwent bedside procedures. Only one trial involved some participants undergoing major surgical operations. Two trials included only participants in intensive care, and two trials included only participants with liver disease. One trial recruited only two participants. Therefore review results include the remaining four trials, incorporating 234 participants. Three further trials are ongoing. When plasma transfusion was compared with no transfusion given, we are very uncertain whether there was a difference in major bleeding, number of blood transfusions per participant, or harmful effects from the transfusion (1 trial; very low-quality evidence). When plasma or platelet transfusion or both were compared with neither plasma nor platelet transfusion, we are very uncertain whether there was a difference in mortality within 30 days, or in the number of individuals requiring a transfusion (1 trial; very low-quality evidence). When plasma transfusion was compared with other haemostatic agents, we are very uncertain whether there was a difference in major bleeding or in harmful effects from the transfusion (1 trial; very low-quality evidence). When different triggers for plasma transfusion were compared (1 trial; 60 participants), we are very uncertain whether there was a difference in major bleeding or in harmful effects from the transfusion due to very low-quality evidence for these outcomes. The number of people requiring blood products may have been reduced overall, although this is based on low-quality evidence. No trials reported procedure-related harmful events or quality of life as an outcome. The overall quality of the evidence was predominantly very low over a range of clinically important outcomes due to combinations of issues within the studies, such as potential for bias, limited clinical settings, and imprecise estimates of intervention effects. We are very uncertain of the effectiveness and safety of the use of plasma in non-cardiac operations or invasive procedures due to very low-quality evidence. Furthermore, as trials do not cover a wide range of surgical contexts, our confidence in applying study results to the wider surgical setting is limited. Overall limited evidence for the utility of plasma transfused to people within this context is of insufficient quality to support or oppose its use.
Psoriasis is a common chronic skin disease with a prevalence in 2% to 3% of the population, according to European studies. Involvement of the nails occurs in about 50%. Nail psoriasis is difficult to treat, but may respond to some treatments. We aimed to review the efficacy and safety of the treatments used for nail psoriasis. We included 18 randomised controlled clinical trials (RCTs), which involved 1266 participants and were mostly based on a single study per treatment. Ten studies assessed topical treatments, i.e. applied to the surface of the skin (clobetasol, ciclosporin in maize oil, hyaluronic acid with chondroitin sulphates, 5-fluorouracil, a combination of dithranol with salicylic and UVB, tazarotene, and calcipotriol); 5 studies assessed systemic treatments, i.e. taken orally (golimumab, infliximab, ustekinumab, ciclosporin, and methotrexate); and 3 studies assessed radiotherapy (electron beam, grenz ray, and superficial radiotherapy). With regard to other treatments that are used for nail psoriasis, no RCTs had been carried out. It was not possible to pool and compare the results because the studies were all so different. In 5 studies, we found significant improvement of nail psoriasis compared to placebo: with infliximab (5 mg/kg), golimumab (50 mg and 100 mg), superficial radiotherapy, electron beam, and grenz rays. Although powerful systemic treatments have been shown to be beneficial, they may have serious adverse effects. So they are not a realistic option for people troubled with nail psoriasis, unless the patient is a candidate for these systemic treatments because of skin psoriasis or psoriatic arthritis. Because of their design and timescale, RCTs generally do not pick up serious side-effects. This review reported only mild adverse effects, recorded mainly for systemic treatments. Radiotherapy for psoriasis is not used in common practice. The evidence for the use of topical treatments is inconclusive and of poor quality; however, this does not imply that they do not work. Topical treatment options could be beneficial and need to be further investigated. Clinical trials on nail psoriasis need to be rigorous in design, with clear reporting to enable readers to better interpret the results. Trials should accurately describe the participants' characteristics and diagnostic features of nail psoriasis; use standard validated nail scores and patient-reported outcomes; be long enough to report efficacy and safety; and include more details of effects on nail features.
The purpose of this review was to assess how effective botulinum toxin is at reducing pain in patients with MPS. We identified four studies, with 233 participants, comparing botulinum toxin A with placebo (control group). There was inconclusive evidence to support the use of botulinum toxin in the treatment of MPS. More high-quality randomised controlled trials of botulinum toxin for treating MPS need to be conducted before firm conclusions on its effectiveness and safety can be drawn.
We searched for all research published up to 1 April 2014, finding 32 relevant studies. There were 19 studies on five anti-TNF biologics (adalimumab, certolizumab, etanercept, golimumab and infliximab) and 12 studies on five non-anti-TNF biologics (abatacept, canakinumab, rituximab, tocilizumab and an anti-interferon gamma monoclonal antibody). Altogether 9,946 participants received biologics and 4,682 participants received standard therapy. All but two of the studies were randomised placebo-controlled trials, the gold standard in terms of study quality. We compared the effects of biologics versus placebo. In some studies, participants may have been taking standard therapy for rheumatoid arthritis at the start of the trial. In these studies, investigators added either biologics or placebo treatment to standard therapy. Overall, treatment by biologics led to small to moderate reductions (9 units reduction on a 0-52 scale) in patient-reported fatigue compared with 3 units in participants treated by placebo. It is unclear whether this improvement is due to a reduction in overall disease activity, a direct effect of the biologics or some other mechanism. There may have been some potential bias in the way investigators analysed data, and some studies did not include all randomised individuals, so we judged the quality of the evidence to be only moderate rather than high.
In human and animal studies however, spontaneous onset of labour is proven to have a circadian rhythm with preference for start in the evening. Moreover, when spontaneous labour starts in the evening, total duration of labour shortens and less obstetric interventions are needed. Based on these observations one might assume, that starting induction of labour in harmony with the circadian rhythm of natural birth is more beneficial. This review found three studies that were of high quality with a total of 1150 women randomly allocated to induction in the morning or the evening. One trial used intravenous oxytocin in women who had a dilated cervix or rupture of membranes and two trials used prostaglandins to induce labour. Prostaglandins are hormones used when the cervix is not ripe, intravenous oxytocin is mostly needed afterwards to really get labour started. Therefore, these two different methods, prostaglandins and intravenous oxytocin, rely on a different mechanism and were assessed separately. This review found no differences in effect between starting induction in morning or evening on outcomes for mother or child. The risk of a vaginal birth using instruments, or risk of a caesarian section and use of epidural anaesthesia did not clearly differ between groups. One study reported that women had a preference to start induction of labour with prostaglandins in the morning, and more women in the evening admission group did not like the interruptions to sleep that were associated with the induction protocol. This review, with only three studies with two different comparisons, concludes that induction of labour in the evening is as effective and safe as induction in the morning. However, given the preference of most women, administration of prostaglandins should preferably be done in the morning.
We found 14 studies involving 698 participants. Whilst all 14 studies compared broadly the analgesic efficacy of PVB and TEB in participants undergoing open thoracotomy, there were significant differences in the timing, method of insertion and medications used in PVB and TEB. This makes direct comparison difficult. Patient follow-up was limited to the immediate post-surgery period (up to five days post-surgery) with only two studies reporting long-term outcomes such as chronic pain. There are two studies awaiting classification. We found no difference between PVB and TEB in terms of death at 30 days and major complications. PVB appeared to be as effective as TEB in pain control post-surgery. TEB was associated with minor complications such as low blood pressure, nausea and vomiting, itching and urinary retention when compared to PVB. We did not find any difference in length of hospital stay between PVB and TEB. There was insufficient information to assess chronic pain and health costs. We found low-quality evidence for death at 30 days, with limited information provided by only two studies reporting this outcome. We only found low to very low-quality evidence for major complications due to lack of information, with only one study reporting these outcomes. We found moderate-quality evidence for acute pain control in the immediate postoperative period. We found moderate-quality evidence for minor complications.
We searched the literature in July 2013 and identified eight randomised controlled trials that compared these two techniques. These included a total of 1708 participants randomly allocated to MSICS or phacoemulsification. The studies were carried out in India, Nepal and South Africa. Not all studies reported the outcomes of visual acuity that we aimed to assess, making it difficult to draw definite conclusions. Better uncorrected visual acuity was seen in the short term with phacoemulsification; however, there were no differences in best-corrected visual acuity (i.e. after correction with spectacles). There appeared to be no significant difference regarding uncorrected visual acuity between the two techniques at six months in the one trial that reported at that time point. There was a lack of long-term data (one year or more after surgery). Very few participants were reported to have poor visual outcomes or complications (such as posterior capsule rupture) from the surgery. The cost of phacoemulsification was documented in one study only, and this was more than four times the cost of MSICS. In this setting, the two techniques appear to be comparable in terms of visual acuity outcomes and complications. However further studies with a longer follow-up period are needed to better assess these outcomes.
We included three clinical trials involving 908 participants. The trials were conducted in Germany and France. All trials compared routine anastomotic drainage versus no anastomotic drainage after elective colorectal surgery. The evidence was current to February 2015. This review showed no apparent difference in anastomotic leak, death, radiological (x-ray) evidence of anastomotic leak, wound infection or need for re-operation. We found insufficient evidence to support the use of routine prophylactic drains after elective colorectal anastomosis. We based our conclusion on limited evidence with relatively small numbers of participants; this means that it is difficult to detect differences between treatment groups that may be present. The quality of the evidence was low, making it impossible to draw firm conclusions about the use of routine prophylactic drains after elective colorectal anastomosis. Additional studies are needed to strengthen the conclusion drawn by this systematic review and to provide further analysis using modern colorectal surgery. We found no new evidence since the previous version of our systematic review of 2004.
We included 10 randomised clinical trials, with a total of 442 participants (mean age 61 years and 42% women). Four included studies recruited people with a range of chronic wounds; three studies enrolled people with venous leg ulcers; and the other three studies included people with diabetes who had foot ulcers. The median length of treatment was 12 weeks. All but three trials reported the sources of funding. Four of the studies received financial support from companies manufacturing PRP devices. The results were non-conclusive as to whether autologous PRP improves the healing of chronic wounds generally compared with standard treatment. Autologous PRP may increase the healing of foot ulcers in people with diabetes compared with standard care, but it is unclear if autologous PRP has an effect on other types of chronic wound. Three studies reported wound complications such as infection or dermatitis, but results showed no difference in the risk of adverse events in people treated with PRP or standard care. These findings are based on low quality evidence due to the small number of studies and patients included, and their poor methodological quality. This Plain Language Summary is up to date as of 16 June 2015.
This summary of a Cochrane review presents what we know from research about the effect of outreach services for patients on general hospital wards. The review found two studies which were of good quality. One study compared 12 hospitals with outreach services to 11 that did not. Another study compared 16 wards with outreach to general wards without outreach. One of the studies showed that outreach reduced the number of hospital deaths, while the other study found no differences between hospitals with outreach and those with no outreach. It is not clear whether outreach reduces hospital deaths or ICU admissions. High quality research is needed to determine the effect of outreach services.
We searched for randomised controlled trials (trials that randomly allocate participants to one of two or more treatment groups) looking at the effectiveness of home-based versus supervised centre-based cardiac rehabilitation programmes, in adults with heart disease. We included 23 trials (2890 participants). Most trials were relatively small (median 104 participants, range: 20 to 525). The average age of trial participants ranged from 51.6 to 69 years. Women accounted for only 19% of recruited participants; four trials did not include women. The mix of people recruited to the trials varied; 10 studies included a mixed population of people with coronary heart disease, five studies included people who had had a heart attack, and four studies each recruited people following revascularisation or who had heart failure. Sixteen studies reported sources of funding; seven did not. No study reported funding from an agency with commercial interest in the results. We found that home- and centre-based cardiac rehabilitation programmes are similar in benefits measured in terms of numbers of deaths, exercise capacity and health-related quality of life. Further data are needed to confirm if these short-term effects of home- and centre-based cardiac rehabilitation can be sustained over time. Poor reporting made it difficult to assess methodological quality of the included studies and their risk of bias. Evidence quality ranged from very low (total mortality), to moderate (exercise capacity over 12 months and health-related quality of life). The main reasons for the low assessment of quality was poor reporting in the included studies.
This review included eight trials in which 2156 patients with breast cancer had randomly received CSFs or placebo or no treatment during chemotherapy. These trials were carried out between 1995 and 2008. Prophylactic treatment with CSFs significantly reduced the risk of developing FN by 73%. The estimated number of patients needed to be treated with CSFs in order to prevent one event of FN was 12. Although a significant decrease in mortality of all causes during chemotherapy and CSF therapy was noted, there was no reduction in infection-related mortality. There was no significant effect observed that planned chemotherapy schedules could be better maintained if CSFs were administered or that the number of patients with neutropenia decreased with CSFs. Notably, CSFs significantly reduced the need for hospital care yet frequently caused short-term adverse effects like bone pain and injection-site reactions. There were several limitations in this analysis: only a few trials could be included, the number of patients was low in many of these trials, and disease stages and chemotherapy treatments varied considerably. Moreover, the trial authors defined their outcomes differently, making comparisons across studies difficult. Information on the primary and secondary outcomes could not be obtained from all trials and the overall reporting quality was low. Many studies were dated and hence the administration of CSFs did not comply with current recommendations. Overall, CSFs have shown moderate evidence of benefit in the prevention of FN in patients with breast cancer receiving chemotherapy. The evidence that the administration of CSFs could reduce early mortality of all causes was weak and substantiates the need of further studies. There was no reduction in risk of infection-related mortality with CSF treatment.
We identified one trial comparing early versus delayed laparoscopic cholecystectomy for people with mild acute pancreatitis. Out of the 50 participants included in this trial, 25 underwent early laparoscopic cholecystectomy while the remaining 25 underwent delayed laparoscopic cholecystectomy. All 50 participants were alive at the end of the trial. There was no significant difference between the two groups in the proportion of participants who developed complications. Health-related quality of life was not reported in this trial. There were no conversions to open cholecystectomy in either group. The total hospital stay was shorter by approximately two days in the early laparoscopic cholecystectomy group than in the delayed laparoscopic cholecystectomy group. The trial did not report the number of work-days lost or the costs. We did not identify any trials comparing early versus delayed laparoscopic cholecystectomy after severe acute pancreatitis. Based on the observations in the one trial included in this review, there appears to be no evidence of increased risk of complications after early laparoscopic cholecystectomy. Early laparoscopic cholecystectomy may shorten the total hospital stay in people with mild acute pancreatitis. If appropriate facilities and expertise are available, early laparoscopic cholecystectomy appears preferable to delayed laparoscopic cholecystectomy in people with mild acute pancreatitis. There is currently no evidence to support or refute early laparoscopic cholecystectomy for people with severe acute pancreatitis. Further well-designed randomised controlled trials are necessary in people with mild acute pancreatitis and severe acute pancreatitis. The one trial identified is at high risk of bias, i.e. there was potential to arrive at wrong conclusions because of the way that the study was designed and conducted.
We searched the literature up to January 2016 and analysed 24 studies that involved 1787 participants. Of these, only seven studies provided data that could be combined for analysis. The studies reported that manual acupressure improved fatigue, depression and sleep disturbance when used as an adjunct to routine care for patients undergoing maintenance haemodialysis 4 weeks from baseline. No study assessed pain and most did not report whether adverse events of acupuncture occurred. Overall, we found very low quality evidence about the effectiveness of acupuncture for symptoms of CKD. Manual acupressure combined with routine care may provide short-term symptom relief from depressive mood, fatigue and sleep disturbance in patients undergoing haemodialysis. Findings from this review cannot support the benefits of other acupuncture techniques for patients with CKD because there were too few reliable studies. Pain is a common condition in patients with CKD. Thus, the potential role of acupuncture for pain control in patients with CKD deserves further research. Clinicians should carefully monitor the safety of acupuncture in patients with CKD unless sound evidence supports the safety of these interventions for CKD patients. All studies were assessed at high or unclear risk of bias, especially in terms of selection of participants and selective outcome reporting, which made the validity of their results doubtful.
We searched scientific databases for clinical studies comparing OGD to capsule endoscopy and reporting the size and appearance of varices in children or adults with chronic liver disease or portal vein thrombosis (narrowing of the portal vein). The evidence is current to October 2013. We found 16 studies assessing the ability of capsule endoscopy to diagnose the presence of varices and grade the risk of bleeding and comparing it with OGD in adults with cirrhosis. Capsule endoscopy, even if more acceptable to participants, cannot replace OGD for the detection of oesophageal varices as about 15% are left undetected and 15% are not confirmed by endoscopy. Even the accuracy in detecting large varices or red marks on varices was very lower than endoscopy. Hence, in conclusion, capsule endoscopy is not sufficiently accurate to replace OGD for the detection of oesophageal varices in cirrhotic participants. In nine of the sixteen studies there were problems concerning participant selection and incompleteness of reported data which impair accuracy estimates and the transferability of the results.
We identified six randomised controlled trials involving a total of 794 women and their babies for this review. The trials were of moderate risk of bias overall. The trials did not demonstrate differences between calcium channel blocker maintenance therapy and placebo or no treatment in the prevention of preterm birth or perinatal death (fetal or neonatal deaths). None of the trials included any follow-up of the infants to assess longer-term development. Calcium channel blocker maintenance therapy (with a drug called nifedipine) was more likely than placebo or no treatment to prolong pregnancy, however the infants of these mothers were more likely to have a longer hospital stay. Based on the current studies, we found no convincing evidence that calcium channel blocker maintenance therapy prevents preterm birth for women after threatened preterm labour, or that it improves outcomes for babies.
This systematic review of randomised controlled trials (RCTs) set out to review the evidence for medication in treating TTM. The findings are based on eight studies (which included a total of 204 people). Not enough evidence was found to conclude definitively that any particular medication is effective in the treatment of TTM. Furthermore, side effects related to medications were not well-documented in the majority of the studies. Because of differences in the way the included studies were carried out, we were unable to combine their results to draw more conclusive evidence. However, an early trial found some evidence for the efficacy of clomipramine, and two recent trials reported statistically significant treatment outcomes with olanzapine and N-acetylcysteine. More research is needed to find an optimal treatment for TTM.
The review of studies found that there was a limited amount of evidence to show that the newer extra-fine form of BDP was similar to FP at the same dose. More research should be done in children and in people with more severe asthma to help answer the question of what the relative effects of these two steroids are. Some people may not be particularly good at using certain inhaler types and the findings of the review may only really apply to people who are competent in using metered-dose inhalers (MDIs). Studies should consider introducing spacers where people find these easier to use.
We included 17 studies evaluating systemic corticosteroid therapy (given intravenously or by tablets) for people with pneumonia (2264 participants; 1954 adults and 310 children). We included 12 new studies in this update and excluded one previously included study. All included studies evaluated people who had acquired pneumonia in the community (community-acquired pneumonia (CAP)) being treated in the hospital; no studies assessed people who had developed pneumonia while in hospital or who were on breathing machines (mechanically ventilated). Eight trials did not report funding sources; seven were funded by academic sponsors; one was funded by a pharmaceutical company; and one reported receiving no funding. Corticosteroids reduced deaths in adults with severe CAP, but not in people with non-severe CAP. Eighteen adults with severe CAP need to be treated with corticosteroids to prevent one death. People with CAP treated with corticosteroids had lower clinical failure rates (death, worsening of imaging studies, or no clinical improvement), shorter time to cure, a shorter hospital stay, and fewer complications. We found good-quality evidence that corticosteroids reduced clinical failure rates in children with pneumonia, but the data were based on a small number of children with different types of pneumonia. People treated with corticosteroids had higher blood glucose levels (hyperglycaemia) than those not treated with corticosteroids. Corticosteroid treatment was not associated with increased rates of other serious adverse events. Corticosteroids were beneficial for adults with severe CAP. People with non-severe CAP may also benefit from corticosteroid therapy, but with no survival advantage. We downgraded the quality of the evidence due to issues with study design, unclear results, or results that were not similar across studies. For the outcomes of death and clinical failure in adults, we graded the quality of the evidence as moderate. For the outcomes of clinical failure in people with severe CAP, non-severe CAP, and in children, we graded the quality of the evidence as high.
Delaying or eliminating the break in hormone use has become a popular way for women to avoid monthly bleeding, so we performed this review to compare these newer regimens to traditional CHC dosing regimens. We searched for all randomized controlled trials on this question in any language; we found twelve that met our criteria. The continuous or extended-cycle and traditional regimens appeared similar, as judged by bleeding, discontinuation rates, and reported satisfaction. The studies were too small to address efficacy, rare adverse events, and safety. Extended-cycle (for more than 28 days) or continuous dosing appears to be a reasonable approach to CHC use.
Some studies have suggested that resecting the primary cancer can prolong survival and prevent complication arising from the cancer, such as obstruction or bleeding. This review addresses the question of whether surgically removing the primary cancer is beneficial to patients with advanced and unresectable colorectal cancer. No randomised controlled trials were identified.
Clinical trials have come to different conclusions about the best approach. We conducted a systematic review and meta-analysis to synthesize available clinical research studies that have examined outcome according to donor vs. no donor status, or genetic randomization. This is a method of analysis for assessing the effect of transplantation in this disease condition. Our analysis supports matched sibling donor allogeneic hematopoeitic cell transplantation as the approach which offers the best long-term outcomes, specifically providing optimal survival and reduced risk for ALL relapse.
However, the review of trials found that drinking clear fluids up to a few hours before surgery did not increase the risk of regurgitation during or after surgery. Some people are considered more likely to regurgitate under anaesthetic, including those who are pregnant, elderly, obese or have stomach disorders. More research is needed to determine whether these people can also safely drink up to a few hours before surgery.
Our review included two randomised controlled trials (involving 154 women) comparing surgical repair of first-degree (involving only the perineal or vaginal skin) or second-degree tears (also involving muscle) with leaving the wound to heal spontaneously. These trials showed no clear differences in clinical outcomes between the groups. The studies did not find any differences in pain immediately and up to eight weeks postpartum. One of the trials reported no difference in wounds complications, but the other showed differences in wound closure and poor wound approximation in the non-sutured group. There was no information about the effect on long-term outcomes such as sexual discomfort or incontinence. More research is needed to provide a strong evidence-based recommendation for clinical practice.
We searched many databases for all papers with FTD and rCBF SPECT as their focus. These papers were reviewed independently by several researchers. After application of inclusion and exclusion criteria, eleven studies including 299 individuals with FTD were available for this review. The studies were published over a 21-year period, with a study size ranging from 27 to 363 participants, mainly recruited from University clinics, tertiary referral centres or memory clinics. Of the 11 studies, three used single-headed (single detector) gamma cameras, a method no longer used in clinical practice today. Evidence is current to June 2013. The majority of studies were at high risk of bias due to insufficient details on how participants were selected and how the rCBF SPECT scans were conducted and analysed. The main limitations of the review were poor reporting, variability of study design and a lack of standardisation of image interpretation between centres. Due to small study numbers and large variation in how the studies were carried out, we are unable at present to recommend the routine use of rCBF SPECT for diagnosing FTD in clinical practice.
This review includes evidence from 19 trials involving 1589 participants, generally aged over 65 years. Many of the trials had weak methods, including inadequate follow-up. There was no pooling of data because no two trials were sufficiently alike. Twelve trials evaluated interventions started soon after hip fracture surgery. Single trials found improved mobility from, respectively, a two-week weight-bearing programme, a quadriceps muscle strengthening exercise programme and electrical stimulation aimed at alleviating pain. Single trials found no significant improvement in mobility from, respectively, a treadmill gait retraining programme, 12 weeks of resistance training, and 16 weeks of weight-bearing exercise. One trial testing ambulation started within 48 hours of surgery found contradictory results. One historic trial found no significant difference in unfavourable outcomes for weight bearing started at two versus 12 weeks. Of two trials evaluating more intensive physiotherapy regimens, one found no difference in recovery, the other reported a higher level of drop-out in the more intensive group. Two trials tested electrical stimulation of the quadriceps: one found no benefit and poor tolerance of the intervention; the other found improved mobility and good tolerance. Seven trials evaluated interventions started after hospital discharge. Started soon after discharge, two trials found improved outcome after 12 weeks of intensive physical training and a home-based physical therapy programme respectively. Begun after completion of standard physical therapy, one trial found improved outcome after six months of intensive physical training, one trial found increased activity levels from a one year exercise programme, and one trial found no significant effects of home-based resistance or aerobic training. One trial found improved outcome after home-based exercises started around 22 weeks from injury. One trial found home-based weight-bearing exercises starting at seven months produced no significant improvement in mobility. In summary, the review found there was not enough evidence to determine which are the best strategies, started in hospital or after discharge from hospital, for helping people walk and continue walking after hip fracture surgery.
We found two randomized trials that had enrolled a total of 216 participants (218 eyes) from Ireland and the United States. Both studies evaluated whether pneumatic retinopexy or scleral buckle was a better treatment for RRD. The study in the US had 198 participants with 6 months to 2 years of follow-up. The study in Ireland had 20 participants with 5 to 27 months of follow-up. The evidence is current to 13 January 2015. Results from both studies suggested that scleral buckle may perform better or as well as pneumatic retinopexy in terms of reattachment rates and reducing the risk of recurrence of detachment. Few ocular adverse events occurred during either procedure and differences in some adverse events occurring after the surgeries could not be determined. More eyes in the scleral buckle group experienced choroidal detachment (separation of the choroid, the layer between the retina and sclera, from the sclera) and myopic shift (change to nearsightedness that may be a sign of developing cataract) than eyes in the pneumatic retinopexy group. The quality of the evidence was assessed as low to moderate due to poor reporting of how the studies were done. Further, there was lack of information regarding important outcomes that may be useful when choosing which procedure to use in terms of vision, quality of life, and cost.
By February 2015 we identified 58 trials for inclusion in the review. The trials involved at total of 2797 participants at all stages of care including being in hospital or back living at home. Most of the people who took part were able to walk on their own. The trials tested different forms of fitness training; these included 1) cardiorespiratory or 'endurance' training, 2) resistance or 'strength' training, or 3) mixed training, which is a combination of cardiorespiratory plus resistance training. We found that cardiorespiratory fitness training, particularly involving walking, can improve exercise ability and walking after stroke. Mixed training improves walking ability and improves balance. However, there was not enough information to draw reliable conclusions about the impact of fitness training on other areas such as quality of life, mood, or cognitive function. Cognitive function is under-investigated despite being a key outcome of interest for stroke survivors. There was no evidence that any of the different types of fitness training caused injuries or other health problems; exercise appears to be a safe intervention. We need more studies to examine the benefits that are important to stroke survivors, in particular for those with more severe stroke who are unable to walk. Studies of fitness training can be difficult to carry out. This means most of the studies were small and of moderate quality. However, some consistent findings did emerge with different studies all tending to show the same effect.
We identified 16 studies of vitamin D preparations in people with CKD and not requiring dialysis (less severe CKD) involving 894 people. No studies were designed to understand the effect of vitamin D therapy on risks of premature cardiovascular disease or mortality. Vitamin D agents lowered PTH significantly compared with no treatment, however also increased both calcium and phosphorus levels. Newer vitamin D therapies have not been compared with older vitamin compounds in CKD directly; whether they are associated with increased calcium and phosphorus is uncertain. In the future, new studies are required to assess outcomes important to patients, such as life expectancy and premature heart disease. It will also be important to know if vitamin D therapy should be used differently (differing target levels of PTH) in differing stages of CKD.
Sixteen trials, involving over one million adults, children, and infants, were included. Injected cholera vaccines reduced the risk of death from cholera and the risk of contracting cholera at 12 months. Significant protection lasted for two years. Injected cholera vaccines had more systemic and local adverse effects than placebo, but these adverse effects were relatively well tolerated and were not severe or life-threatening. The authors conclude that injected cholera vaccines appear to be relatively safe and more effective than usually realized. However, they are not currently available and therefore cannot be recommended for use. This review provides a solid background of evidence for the effects of cholera injected vaccines, against which to compare the effects of oral vaccines.
We found two randomised controlled trials which enrolled a total of 215 participants. One trial, published in 2011, was conducted in 193 infants aged 9 months to 18 months and compared the drug hydroxyurea to placebo. The second trial, published in 1998, was conducted in 22 adults with normal blood pressure and microalbuminuria (an increase of protein in the urine) and compared captopril (a drug used to treat high blood pressure) to placebo. Both trials received government funding. In infants aged 9 months to 18 months, hydroxyurea may increase the ability to produce normal urine, but we are very uncertain if it has any effect on the glomerular filtration rate (network of filters in the kidney that filter waste from the blood). Hydroxyurea may make little or no difference on the incidence of SCD-related serious complications (including acute chest syndrome, painful crises and hospitalisations). We are very uncertain if giving captopril to adults with SCD who have normal blood pressure and early signs of kidney damage (microalbuminuria) reduces progression of kidney damage. Quality of life was not reported in either trial. The evidence for all outcomes was rated as low- to very low-quality due to trials being at high risk of bias and because there were a small number of trials and a small number of participants included in the trials.
Disability: One study found that at three weeks after treatment, people's disability was improved by 11 points on a scale of 0-100, possibly as few as 4 or as many as 11 points on a scale of 0-100. Another study found disability was improved by 17 points. This improvement could possibly be as low as 6 or as many as 28 points on a scale of 0-100. At six weeks after treatment, people's disability was improved by 46 points on a scale of 0-500. This improvement could possibly be as little as 20 points or as many as 80 points on a scale of 0-500. At 12 weeks after treatment, people's disability was improved by 54 points on a scale of 0-500. This improvement could be as little as 15 points or as many as 95 points on a scale of 0-500. The numbers given are our best estimate. When possible, we have also presented a range because there is a 95 percent chance that the true effect of the treatment lies somewhere between that range.
We included six studies that involved 483 participants (298 male, 185 female) over the age of 18 years. Participants had received breathing support from a machine (been mechanically ventilated) for longer than 24 hours whilst in the ICU and had begun an exercise programme after leaving the ICU. Studies were carried out in the UK, Australia, the USA and Italy. Exercise programmes were delivered on the ward in two studies; on the ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to length of hospital stay after ICU discharge up to a fixed time of 12 weeks. Exercises included arm or leg cycling, walking and general muscle strengthening at home, provision of self help manuals and hospital-based multi-exercise programmes carried out in physiotherapist-led gymnasiums. Three of the six studies were funded by government health research funding agencies. One study was supported by combined funding from an independent charity and a commercial company (with no interest in the results of the study). One study did not report a funding source, and another was funded by an academic health research agency. We were unable to determine an overall result for the effects of exercise-based interventions. Three studies reported improvement in functional exercise capacity following completion of the exercise programme, and the other three found no effects of treatment. Only two studies measured patient-reported health-related quality of life, and both of these studies showed no effects related to treatment. Again, we were unable to reach an overall conclusion. No study included an evaluation of acceptance of the treatment by patients or the experience of patient participation in an exercise-based programme. We found considerable differences across included studies regarding types of exercise, how measurements of functional exercise capacity were collected, ways by which results were presented and people who had been critically ill. Exercise programmes were compared with usual care, with lack of acknowledgement of the standard level of rehabilitation and exercise in usual practice. In addition, we found variability in how well the studies were performed. We were unable to perform any statistical tests on study findings or to make firm conclusions because of this variability. The overall quality of the evidence was very low for these reasons. . Evidence is current to May 2014. We reran the search in February 2015 and will deal with studies of interest when we update the review.
We identified 12 randomised clinical trials involving 734 patients that compared miniport laparoscopic cholecystectomy (380) with standard port laparoscopic cholecystectomy (351). The choice of the treatment that the patients received was determined by a method similar to toss of coin so that both treatments were conducted in patients who were as similar as possible. Most of the trials were of high risk of bias, i.e. there is possibility of arriving at wrong conclusions overestimating benefits or underestimating harms because of study design. Miniport laparoscopic cholecystectomy could be completed successfully in more than 80% of patients in most studies. The remaining patients were mostly converted to standard port laparoscopic cholecystectomy but some patients had to undergo open cholecystectomy. These patients were excluded from the analysis by the study authors and so the results of these trials as well as the present systematic review have to be interpreted with extreme caution. There was no mortality in either group in the seven trials that reported mortality (0/226 patients versus 0/234 patients). There were no significant differences between the two operation types in the proportion of patients who developed serious complications, quality of life at 10 days after operation, or in whom the laparoscopic operation had to be converted to open cholecystectomy. Miniport laparoscopic cholecystectomy took five minutes longer to complete than standard port laparoscopic cholecystectomy. There were no significant differences between the two operation types in the length of hospital stay, the time taken to return to activity, or in the time taken to return to work. There was no significant cosmetic difference at six months to 12 months after surgery between the two groups, in the two trials that reported this outcome. There appears to be no advantage of miniport laparoscopic cholecystectomy in terms of decreasing surgical complications, hospital stay, return to activity, return to work, or improving cosmesis. On the other hand, there is a modest increase in operating time after miniport laparoscopic cholecystectomy compared with standard port laparoscopic cholecystectomy. The safety of miniport laparoscopic cholecystectomy is yet to be established. Miniport laparoscopic cholecystectomy cannot be recommended routinely outside well-designed randomised clinical trials. Further well-designed randomised clinical trials are necessary to determine whether miniport laparoscopic cholecystectomy is safe and whether there is any advantage over standard port laparoscopic cholecystectomy.
The evidence is current to January 2019. We found two randomized studies (clinical studies where people are randomly put into one of two or more treatment groups) and one controlled study (clinical studies where people are put into one of two or more treatment groups but this is not done in a random way) (149 participants), all comparing amifostine with no additional treatment. Two studies included children with osteosarcoma (a type of bone cancer), the other study included children with hepatoblastoma (a type of liver cancer). Combining the results of the included studies was not possible. It is not clear how long participants were monitored. We also found one randomized study (109 children with localized hepatoblastoma) comparing sodium thiosulfate with no additional treatment. Half of the participants were monitored for more than four years. At the moment there is no evidence from individual studies showing that the use of amifostine prevents hearing loss. Only one study reported results on cancer response and side effects, so we could make no definitive conclusions. None of the studies assessed survival and quality of life. Hearing loss seemed to be lower with the use of sodium thiosulfate, but the effect of sodium thiosulfate on cancer response and side effects was uncertain. We identified no adequate studies for other possible drugs to prevent hearing loss and for other types of cancer. Before definitive conclusions can be made about the usefulness of possible medicines to prevent hearing loss (amifostine, sodium thiosulfate or another medicine) in children treated with platinum chemotherapy more high-quality research is needed. The quality of the evidence was moderate (for hearing loss with sodium thiosulfate) to low (for all other outcomes (results)). The quality of the evidence was limited because of issues with the study design (for all outcomes) and small numbers of participants in each study (for all outcomes except hearing loss with sodium thiosulfate).
This review evaluated the effectiveness and safety of topical 5-FU for treatment of genital warts in nonimmunocompromised individuals. Evidence from the studies we reviewed showed that 5-FU had better results for cure than placebo or no treatment; MCSA; and Podophylin 2%, 4% or 25%. No statistical difference was found when 5-FU was compared with CO2 Laser treatment, and results were poor when 5-FU was compared with 5-FU + INFα-2a (high dose) or 5-FU + CO2 Laser INFα-2a (high dose). The weak point of this review was the great variability in the methods and quality of the studies that we included.
The evidence included in this review is current to April 2015. We included 11 studies on combinations of several testing methods involving 1339 participants. All studies evaluated women of reproductive age who were undertaking diagnostic surgery to investigate symptoms of endometriosis or for other indications. Fifteen combinations of different blood, endometrial and urinary biomarkers were studied, incorporating ultrasound, clinical history and examination. Each combination of tests was assessed in small individual studies. Several studies identified the combined tests that might be of value in diagnosing endometriosis, but there are too few reports to be sure of their diagnostic benefit. The reports were of low methodological quality, which is why these results cannot be considered reliable unless confirmed in large high-quality studies. Overall, there is not enough evidence to demonstrate benefit of any combined non-invasive test for use in clinical practice for the diagnosis of endometriosis over the current ‘gold standard’ of diagnostic laparoscopy. More high-quality research studies are needed to accurately assess the diagnostic potential of any type of non-invasive tests or their combinations that were identified in only a few studies as possibly having value in the detection of endometriosis.
We found three trials, involving 189 participants, which showed improvement in hearing thresholds in those treated with vasodilators compared to control groups. However, as the number of patients included in the studies was small, and there were differences in the type, dosage and duration of vasodilator treatment used in each of these studies, the results could not be combined to reach a conclusion. The effectiveness of vasodilators in the treatment of ISSHL could not be proven. Further research is needed.
Recent studies showed that a class of white blood cells (B lymphocytes) can be involved in the pathology of MS. This feature has led to a renewed interest in therapies directed at controlling B-cell activity. Rituximab belongs to the class of monoclonal antibodies and is able to diminish the number of B lymphocytes in the cerebrospinal fluid. The authors of this review assessed the efficacy and safety of rituximab in patients with RRMS, taking into account relapses, brain lesions and disease progression. From the pertinent literature, only one study evaluating rituximab versus placebo in 104 adult patients with at least one relapse during the preceding year was included. The authors did not find convincing evidence to support rituximab as an effective treatment for RRMS, also because the quality of the one identified study was limited due to high attrition bias, the small number of participants, and short follow-up. As far as safety is concerned, patients reported infusion-associated adverse events within the 24 hours after the first infusion, including chills, headache, nausea, pyrexia, pruritus, fatigue, throat irritation and pharyngolaryngeal pain. Among infection-associated adverse events, only urinary tract infections (in 14.5% versus 8.6%) and sinusitis (13.0% versus 8.6%) were more common in the rituximab group. The potential benefits of rituximab for treating RRMS need to be further evaluated in large-scale studies that are of high quality along with long-term safety.
This review found three studies involving 351 participants evaluating the effectiveness of different antibiotic therapies in adults with acute laryngitis. The evidence is current to December 2014. We ranked the quality of the evidence as low to very low, mainly because many studies had methodological limitations, outcome results were based on limited numbers of trials and the trials included participants that could not be pooled. We found that penicillin V and erythromycin appear to have no benefit in treating acute laryngitis. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. Fusafungine could improve the rates of cured patients at day five. Overall, there is no clear benefit for the primary outcome, which is an objective assessment of voice quality, but some improvements are seen in subjective measures (i.e. cough, hoarseness of voice) that could be important to patients. However, we consider that these modest benefits from antibiotics may not outweigh their cost, adverse effects or negative consequences for antibiotic resistance patterns. The implications for practice are that prescribing antibiotics should not be done in the first instance as they will not objectively improve symptoms
We looked for studies that enrolled adult smokers who were either in treatment or had completed treatment for substance abuse, in hospital, outpatient or community settings and randomised them to either a treatment to help them stop smoking or a control. We last searched for evidence in August 2016. We found 34 published studies. The types of smoking cessation treatment tested included: counselling (which might be a brief advice session or multiple sessions of behavioural support, either individually or in a group); medicine (called pharmacotherapy; including any type of nicotine replacement therapy, with or without other medicines that help smokers to stop smoking); or a combination of counselling and pharmacotherapy. We combined the results of trials separately for each of these types of treatment, although different trials used different treatments. People who were in the control groups received usual care, brief advice about quitting smoking, or were put on a waiting list to receive treatment later. Most trials assessed the number of people who had quit smoking at least six months after beginning treatment although we also included some studies with a shorter time. Eleven studies with 1808 people tested the effects of various types of pharmacotherapy. There was evidence that people given pharmacotherapy were more successful at quitting smoking. Twelve studies with 2229 participants tested treatments that combined pharmacotherapy and counselling. There was evidence that people given combined treatments were more successful at quitting smoking. Eleven studies with 1759 people tested the effect of counselling compared to usual care. Combining these results did not show evidence of a benefit of counselling alone. Eleven studies with 2231 people reported whether people remained abstinent from alcohol and other drugs. Providing tobacco cessation interventions did not make people more likely to return to using alcohol or other drugs. We found no evidence that it made a difference whether people were given treatment to quit smoking when they were just starting treatment for other drug use or after they were in recovery. Results were also similar for people who were treated for alcohol use and for people who were treated for other drugs such as heroin. We judged the quality of the evidence to be low. Many studies did not give enough details about the methods that they used. The studies also considered very different types of treatment, making comparisons challenging.
This review of trials found only four studies which had an overall low quality. Three trials showed no significant differences between momordica charantia and placebo or antidiabetic drugs (glibenclamide and metformin) in the blood sugar response. The duration of treatment ranged from four weeks to three months, and altogether 479 patients with type 2 diabetes mellitus participated. No trial investigated death from any cause, morbidity, health-related quality of life or costs. Adverse effects were mostly moderate, including diarrhoea and abdominal pain. However, reporting of adverse effects was incomplete in the included studies. There are many varieties of preparations of momordica charantia, as well as variations in its use as a vegetable. Further studies are needed to assess the quality of the various momordica charantia preparations as well as to further evaluate its use in the diet of diabetic people.
The evidence from randomized controlled trials is current to January 2018. We included five trials with 666 adults in the review. Three studies are ongoing. All participants were taking antiplatelet therapy (aspirin or clopidogrel) at the start of the study. Two studies stopped antiplatelet drugs for at least five days before surgery, and three studies gave participants a placebo instead of antiplatelet therapy during this time. We found low-certainty evidence that either continuing or stopping antiplatelet therapy may make little or no difference to the number of people who died up to 30 days or six months after surgery (five studies, 659 participants). We found moderate-certainty evidence that either continuing or stopping antiplatelet therapy probably makes little or no difference to incidences of bleeding serious enough to need a blood transfusion during or immediately after surgery (four studies, 368 participants). We found low-certainty evidence that either continuing or stopping antiplatelet therapy may make little or no difference to bleeding serious enough to need further surgery (four studies, 368 participants), and may make little or no difference to the number of ischaemic events such as stroke or heart attack (four studies, 616 participants). Some studies had low risk of bias because they had clearly reported their methods for randomizing people to each group, and three studies used a placebo agent so that people did not know whether or not they were continuing their usual antiplatelet therapy. However, we found few studies with few events, with wide variation in results. To continue or stop taking antiplatelet drugs for a few days before non-cardiac surgery might make little or no difference to the number of people who died, who had bleeding that needed further surgery or who had ischaemic events, and it probably makes little or no difference to bleeding that needed a blood transfusion. We found three ongoing studies which will increase certainty in the effect in future updates of the review.
We searched up to July 2019 for all studies that assessed the use of MNP for improving the health and nutrition of children under two years of age. We included 29 studies that involved 33,147 infants and young children from low- and middle-income countries in Asia, Africa, Latin America, and the Caribbean. Twenty-six studies with 27,051 children contributed data. Of these 26 studies, 24 compared the use of MNP versus no intervention or placebo, and 2 compared the use of MNP versus an iron-only supplement (iron drops) given daily. We found that a variety of MNP formulations containing between 5 and 22 vitamins and minerals were given for 2 to 44 months to infants and young children aged 6 to 23 months. Most studies were funded by government programmes or foundations; only 2 were funded by industry. The use of MNP containing at least iron, zinc, and vitamin A for home fortification of foods was associated with reduced risk of anaemia of 18% and iron deficiency of 53% in children aged six months to two years compared with no intervention. Also, haemoglobin concentration and iron status improved. Studies did not find any effects on growth. There was no additional benefit in reducing risk of anaemia and improving haemoglobin concentration compared to usually recommended iron drops or syrups; however, only two studies compared these different interventions. No trials reported death attributable to the intervention. Information on deaths, side effects, and morbidity, including malaria and diarrhoea, was scarce. The use of MNP was beneficial for young children 6 to 23 months of age, independent of whether they lived in settings with different anaemia and malaria backgrounds and regardless of the length of the intervention. MNP is better than no intervention or placebo and may be comparable to daily iron supplementation.The benefits of this intervention as a child survival strategy or for developmental outcomes are still unclear, and further investigation is required. MNP intake adherence was variable and in some cases comparable to that achieved in infants and young children receiving standard iron supplements as drops or syrups. For the comparison of MNP versus no intervention or placebo, we judged the certainty of evidence to be moderate for anaemia and high for iron deficiency. The certainty of evidence for all other outcomes in this comparison was either low or moderate. Two trials that compared the use of MNP versus iron supplement showed similar effects on anaemia and haemoglobin but less diarrhoea; however, we judged the certainty of evidence as low for anaemia and very low for haemoglobin concentration due to the small number of study participants.
This review aimed to assess whether additional monies provided to socially or economically disadvantaged families could affect children's health, well-being and educational attainment. Nine studies were identified that met inclusion criteria. There was tentative evidence of benefit in early language development, but given lack of effect on all other outcomes, authors conclude that the evidence did not show an effect on child outcomes in the short to medium term in response to direct financial benefits to families. In the context of the monetary value of interventions observed, and the conditions placed on receipt of benefits, authors conclude this is a statement of "no evidence of effect" rather than "evidence of no effect". Implications for research and practice are noted.
Overall, we found 10 studies evaluating different non-medication treatments to treat chronic pain in persons with MS. The treatments evaluated included: transcutaneous electrical nerve stimulation, transcranial direct stimulation, transcranial random noise stimulation, reflexology, psychotherapy and hydrotherapy. These studies included 565 participants and used a range of different methods to measure pain and other outcomes. Comparison groups also varied. Results from these studies show a very low level of evidence for the use of any non-medication treatments for chronic pain in persons with MS. We assessed the overall quality of the studies as very low, as many studies included only small numbers of participants and had other methodological issues. More research with good methodological quality and greater number of participants are needed to determine the effectiveness of such treatments.
In January 2016, we identified 21 Cochrane Reviews which covered 10 different diagnoses (osteoarthritis (a joint disease), rheumatoid arthritis (joint pain and swelling), fibromyalgia (widespread pain condition), low back pain, intermittent claudication (cramping pain in the legs), dysmenorrhoea (period pain), mechanical neck disorders (neck pain), spinal cord injury, postpolio syndrome (a condition occurring in people who have had polio), patellofemoral pain (pain at the front of the knee)). The physical activity or exercise programme used in the trials ranged in frequency, intensity, and type, including land- and water-based activities, those focusing on building strength, endurance, flexibility and range of motion, and muscle activation exercises. The quality of the evidence was low. This was mostly due to the small numbers of people with chronic pain who participated in each reviewed study. Ideally, a study should have hundreds of people assigned to each group, whereas most of the studies included in the review process here had fewer than 50 people in total. There was evidence that physical activity reduced the severity of pain, improved physical function, and had a variable effect on both psychological function and quality of life. However, these results were not found in all studies. The inconsistency could be due to the quality of the studies or because of the mix of different types of physical activity tested in the studies. Additionally, participants had predominantly mild-to-moderate pain, not moderate-to-severe pain. According to the available evidence (only 25% of included studies reported on possible harm or injury from the intervention), physical activity did not cause harm. Muscle soreness that sometimes occurs with starting a new exercise subsided as the participants adapted to the new activities. This is important as it shows physical activity in general is acceptable and unlikely to cause harm in people with chronic pain, many of whom may have previously feared it would increase their pain further. Future studies should focus on increasing participant numbers, including a wider range of severity of pain (more people with more severe pain), and lengthening both the intervention (exercise programme) itself, and the follow-up period. This pain is chronic in nature, and so a long-term intervention, with longer periods of recovery or follow-up, may be more effective.
The review shows that while combined chiropractic interventions slightly improved pain and disability in the short term and pain in the medium term for acute and subacute low-back pain, there is currently no evidence to support or refute that combined chiropractic interventions provide a clinically meaningful advantage over other treatments for pain or disability in people with low-back pain. Any demonstrated differences were small and were only seen in studies with a high risk of bias. Future research is very likely to change the results and our confidence in them. Well conducted randomised trials are required that compare combined chiropractic interventions to other established therapies for low-back pain.
We found three randomised controlled trials, conducted at diabetes clinics in the USA. The total number of participants in the studies was 254. The participants were all adolescent girls involved in the programme READY-Girls (Reproductive-health Education and Awareness of Diabetes in Youth for Girls). Their care was compared with standard care. None of these three trials gave us the information on the health outcomes we needed. In one trial, there were no pregnancies among the participants during the period of the study, and the other two trials’ reporting of pregnancy was not sufficient. There were no data about short and long term outcomes for the mothers and their babies, or about the use of the health service and related costs. Because the information is lacking, we have no evidence from this Cochrane review to guide practice on this topic. Further large, well-designed, randomised controlled trials are required. Three trials are ongoing and will be considered in the next update of this review.
Based on seven studies (1432 people), of overall moderate quality, injecting antibodies into a muscle of people who came into contact with measles, but lacked their own antibodies, was effective at preventing them catching the disease compared to those who received no treatment. Using the modern day antibody preparation, people were 83% less likely to develop measles than those who were not treated. It was very effective at preventing them developing complications if they did contract measles and very effective at preventing death. The included studies generally did not intend to measure possible harms from the injections. Minor side effects were reported, such as muscle stiffness, redness around the injection site, fever and rash. Importantly, only two studies compared the measles vaccine with the antibody injection in this group of people, so no firm conclusions could be drawn about the relative effectiveness of these interventions. The antibody injection is often recommended for pregnant women, infants and immunocompromised people (if they do not have their own antibodies to measles and come into contact with someone who is contagious with measles). The included studies did not include these groups of people, so it is unknown whether the effectiveness of antibody injections is different for them. We were also unable to identify the minimum dose of antibodies required as only one study measured the specific amount of measles antibodies in the injections and one other study estimated this figure; the results of these two studies were not consistent. The evidence is current to August 2013.
We found 37 randomised controlled trials (RCTs) of 3872 women comparing the use of GnRHa in various protocols. Twenty of these RCTs (1643 women) compared a long protocol with a short protocol. The evidence is current to April 2015. In comparisons of long GnRHa protocols (where GnRHa is given for at least 14 days prior to the start of ovarian stimulation) versus short GnRHa protocols (when the GnRHa is given at the start of stimulation) there was no conclusive evidence of a difference in live birth and ongoing pregnancy rates. However there was moderate quality evidence of higher clinical pregnancy rates in the long protocol groups. Our findings suggest that in a population in which 14% of women achieve live birth or ongoing pregnancy using a short protocol, between 13% and 23% will achieve live birth or ongoing pregnancy using a long protocol. None of the other analyses showed any evidence of a difference in birth or pregnancy outcomes between the protocols compared. There was insufficient evidence to make any conclusions regarding adverse effects. Further research is needed to determine which long protocol is most cost effective and acceptable to women. The quality of the evidence ranged from moderate to low. The main limitations in the evidence were failure to report live birth or ongoing pregnancy, poor reporting of methods in the primary studies, and imprecise findings due to lack of data. Only 10 of the 37 included studies were conducted within the last 10 years.
In this Cochrane Review, 12 trials including 754 participants met our inclusion criteria. Eight of the 12 trials reported that the aerobic exercise interventions resulted in increased fitness of the trained group. However, when we combined results across the trials, we did not find any significant benefits of aerobic exercise or increased fitness on any aspect of cognition. Many included trials had problems with their methods or reporting which reduced our confidence in the findings. We did not find evidence that aerobic exercise or increased fitness improves cognitive function in older people. However, it remains possible that it may be helpful for particular subgroups of people, or that more intense exercise programmes could be beneficial. Therefore further research in this area is necessary.
We included 37 studies in which more than 15,000 children (aged six to 14 years) were treated with fluoride mouthrinse or placebo (a mouthrinse with no active ingredient) or received no treatment. All studies assessed supervised use of fluoride mouthrinse in school settings, with two studies also including home use. Most children received a sodium fluoride (NaF) solution, given at 230 parts per million of fluoride (ppm F) daily or a higher concentration of 900 ppm F weekly or fortnightly. Studies lasted from two to three years. Reports were published between 1965 and 2005, and studies took place in several countries. This review update confirmed that supervised regular use of fluoride mouthrinse can reduce tooth decay in children and adolescents. Combined results of 35 trials showed that, on average, there is a 27% reduction in decayed, missing and filled tooth surfaces in permanent teeth with fluoride mouthrinse compared with placebo or no mouthrinse. This benefit is likely to be present even if children use fluoride toothpaste or live in water-fluoridated areas. Combined results of 13 trials found an average 23% reduction in decayed, missing and filled teeth (rather than tooth surfaces) in permanent teeth with fluoride mouthrinse compared with placebo or no mouthrinse. No trials have looked at the effect of fluoride rinse on baby teeth. We found little information about unwanted side effects or about how well children were able to cope with the use of mouthrinses. Regular use of fluoride mouthrinse under supervision results in a large reduction in tooth decay in children's permanent teeth. We found little information about potential adverse effects and acceptability. Available evidence for permanent teeth is of moderate quality. This means we are moderately confident in the size of the effect. Very little evidence is available to assess adverse effects.
The researchers identified six studies that included a total of 517 participants. Five studies (total 485 participants) compared type I IFNs to placebo (fake medicine) injections. One small (32 participants) low quality study compared types I IFNs to prednisolone (a steroid drug) enemas. This study did not measure remission and found no difference between the treatment groups in quality of life or disease activity scores. There was no difference between type I interferons and placebo treatment groups for the number of people who achieved remission or improvement of their symptoms. These results suggest that type I IFNs do not produce remission from ulcerative colitis. Common side effects included headaches, arthralgias (joint pain), myalgias (muscle pain), fatigue, back pain, nausea, injection site reactions, rigors (cold and shivering), and fevers. At present, the results from medical trials do not support the use of type I IFNs for the production of remission in active ulcerative colitis.
We included two randomised controlled trials of moderate quality, including 260 children with measles, comparing children given vitamin A with children not given vitamin A. The evidence is current to December 2015. Two doses of vitamin A given on two consecutive days to hospitalised children with measles led to an increase in the blood concentration of vitamin A after one week. However, there is a limitation in that neither of the two included studies reported blindness or other eye problems in children infected with measles. Also, no side effects of the treatment were reported in the included studies. We do not have sufficient evidence to demonstrate the benefit or otherwise of vitamin A in the prevention of blindness in children infected with measles. The quality of the evidence and methodology of both studies was moderate. The sample size of the included studies was relatively small, which could affect the accuracy of the results.
This systematic review included eight cohort studies and two randomised studies with a total number of 298 patients. All studies assessed adrenal function in paediatric patients treated with glucocorticoids for ALL. The evidence is current to December 2016. None of these studies assessed the HPA axis at the level of the hypothalamus, the pituitary, or both. We could not combine the results of different studies because of heterogeneity. Adrenal insufficiency occurred in nearly all children during the first days after completion of glucocorticoid therapy. Most children recovered within a few weeks, but a small number had ongoing adrenal insufficiency lasting up to 34 weeks. Three studies looked into differences in duration of adrenal insufficiency between children who received prednisone and those who were given dexamethasone (two types of glucocorticoids). Two of these three studies found no differences. In the other study, children who received prednisone recovered earlier than those who received dexamethasone. Also, treatment with a certain antifungal drug (fluconazole) seemed to prolong the duration of adrenal insufficiency. Two studies investigated this. Finally, two studies evaluated the presence of infection/stress as a risk factor for adrenal insufficiency. One study found no relationship. The other study reported that increased infection was associated with a longer duration of adrenal insufficiency. More high-quality research is needed to define the exact occurrence and duration of HPA axis suppression. Then adequate guidelines for glucocorticoid replacement therapy can be formulated. All of the included studies had some risk of bias issues.
The objective was to assess the benefits of the treatment [sulfasalazine, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, methotrexate] for psoriatic arthritis and to assess the side effects. Parenteral methotrexate and sulfasalazine resulted in important benefit in over half the patients for psoriatic arthritis in these studies. There was insufficient data to evaluate other therapies and to examine toxicity. Further multicentre trials are required to establish the efficacy of azathioprine, oral methotrexate, etretinate, and colchicine.
We searched for evidence on 30th November 2016 and identified five trials with a total of 1159 pregnant women. All five trials used X-ray pelvimetry in comparison to no X-ray pelvimetry. The women who received X-ray pelvimetry were more likely to have a caesarean section (low-quality evidence). Whether a woman had pelvimetry or not, we found no difference in the numbers of babies that died (very low-quality evidence), who did not have enough oxygen during labour, or were admitted to special care baby units (very low-quality evidence). For the women, no differences were found between numbers of women with wound sepsis, those who received a blood transfusion, or those whose caesarean section scar began to break down (all very low-quality evidence). Apgar score less than seven at five minutes was not reported in any study. There is too little evidence (the majority of which is low quality) to show whether measuring the size of the woman's pelvis (pelvimetry) is beneficial and safe when the baby is in a head-down position. The number of women having a caesarean section increased if women had X-ray pelvimetry but there was insufficient good-quality evidence to show if pelvimetry improves outcomes for the baby. More research is needed.
We searched for all randomised controlled trials (RCTs) that assessed the efficacy and safety of anti-TNF agents for the treatment of long-term plaque psoriasis in individuals younger than 18 years of age. We searched databases up to July 2015. Only one study (with three phases: a 12-week randomised, double-blind, placebo-controlled phase; a 24-week open-label phase, and a 12-week phase of a randomised, double-blind, withdrawal–retreatment design) investigating one anti-TNF agent (etanercept) in 211 participants met the inclusion criteria. Evidence from this single included study suggests that by week 12 etanercept reduced the extent of the psoriasis in children when compared with placebo. Although a few adverse events were reported, they were resolved without subsequent problems. We did not find any evidence on long-term side effects of this drug from this included study. Although this one RCT provided high-quality evidence for the Physician's Global Assessment and all Psoriasis Area and Severity Index scores (75, 90, and 50) and moderate-quality evidence for quality-of-life outcomes, we found no further randomised studies either evaluating etanercept or comparing other anti-TNF agents, highlighting the need for further well-designed randomised studies involving the use of biological therapies in children and young people with psoriasis. Several studies are ongoing that have not yet been completed or published. We plan to include the results of these in future updates of this review.
This review included 10 studies and 510 patients. All studies included a similar population of people with non-specific low back pain. The studies only included participants with chronic low back pain. The duration of the treatment programmes in the included trials ranged from 10 days to 90 days. The duration of follow-up varied from four weeks to six months. None of the included studies measured follow-up beyond six months. The sample sizes ranged from 17 to 87 participants. The included studies demonstrated that Pilates is probably more effective than minimal intervention in the short and intermediate term for pain and disability outcomes, and more effective than minimal intervention for improvement in function and global impression of recovery in the short term. Pilates is probably not more effective than other exercises for pain and disability in the short and intermediate term. For function, other exercises were more effective than Pilates at intermediate-term follow-up, but not at short-term follow-up. Thus, while there is some evidence for the effectiveness of Pilates for low back pain, there is no conclusive evidence that it is superior to other forms of exercise. Minor or no adverse events were reported for the interventions in this review. The overall quality of the evidence in this review ranged from low to moderate.
In February 2017, we searched for clinical trials in which morphine was used to treat neuropathic pain in adults. Five studies satisfied the inclusion criteria, randomising 236 participants to treatment with morphine, placebo, or other drugs. Studies lasted four to seven weeks. Few studies reported beneficial outcomes that would be regarded as clinically relevant. Four small studies reported that pain was reduced by between a quarter and a third in some people. This level of pain reduction was experienced by 6 in 10 participants with morphine and 4 in 10 with placebo. Between 1 and 2 in 10 participants withdrew from treatment with both morphine and placebo, but the reasons were not given. Side effects were poorly reported, but were more common with morphine than with placebo, and included drowsiness, dizziness, constipation, feeling sick, dry mouth, and decreased appetite. The evidence was of very low quality. This means that the research did not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is very high. Small studies like those in this review tend to overestimate results of treatment compared to the effects found in larger, better designed studies. There were other problems that might lead to over-optimistic results. The very low quality evidence and the lack of any important benefit mean that we need new, longer-lasting, large trials before we will know if morphine is useful for the treatment of neuropathic pain.
- More people who received epoetin or darbepoetin died during and up to 30 days after the end of study compared with people who took placebo or underwent standard treatment. The increased risk for people taking epoetin or darbepoetin was 17%. One hundred and fourteen out of 1,000 persons receiving epoetin or darbepoetin died, compared with 98 out of 1,000 persons not receiving epoetin or darbepoetin. We could not identify particular characteristics of people or treatment strategies that increased or decreased the risk for dying. - Concerning long-term survival people taking epoetin or darbepoetin were 5% more at risk for dying than people taking placebo or receiving standard treatment. - People receiving epoetin or darbepoetin rated their fatigue symptoms to be an average of 2.08 points improved on a scale of 0-52 points after 3-4 months, compared with people taking placebo or having standard treatment. This improvement, however, is less than the 3.0 point increase which is considered to be the minimum required for the patient to feel a difference in his experience of fatigue-related symptoms using this scale. - People taking epoetin or darbepoetin rated their fatigue and anaemia symptoms had to be an average of 6.14 points improved after three to four months, on a scale of 0-80 points. This improvement is considered to reflect a positive change in the way patients experience their fatigue and anaemia related symptoms, as it is more than four to five points of increase which is the minimum required for this scale. - Seven people out of 100 who took epoetin or darbepoetin suffered a thromboembolic event such as stroke and myocardial infarction compared with five people out of 100 who did not receive epoetin or darbepoetin. - Six out of 100 people receiving epoetin or darbepoetin developed high blood pressure compared with four out of 100 people who took placebo or had standard care.
In October 2016, we searched for clinical trials on early palliative care in adults with advanced cancer. We included seven studies and found 20 ongoing studies. Most of the studies included participants older than 65 years of age on average, diagnosed with different tumour types and receiving treatment in tertiary care centres in North America. Most of these studies compared early palliative care with standard oncological (cancer) care. All studies were funded by government agencies. When evaluated together in a meta-analysis, studies showed that in patients with advanced cancer, early palliative care may slightly increase quality of life. It may also decrease symptom intensity to a small degree. Effects on survival and depression are uncertain. A single study reported side effects (adverse events), for example, more pain and reduced appetite. For the remaining six studies, information about side effects was not published, but trial authors told us they had not observed any. We rated the certainty of the evidence using four levels: very low, low, moderate, and high. Evidence of very low certainty means that we have little confidence in the results. Evidence of high certainty means that we are very confident in the results. We found that certainty of the evidence was low for health-related quality of life and symptom intensity, and was very low for depression and survival. We downgraded certainty of the evidence for various reasons, for example, problems in the way studies were carried out, differences between studies, and the small number of studies. We remain uncertain about the effects of early palliative care; therefore we have to interpret the results with caution. When published, ongoing studies may provide more evidence, and this may affect the certainty of the results.
The orally-administered cytotoxic, hydroxyurea, may be given alongside radiotherapy for treating cervix cancer. Eight trials comparing concomitant hydroxyurea and radiotherapy with radiotherapy alone were assessed. They were not of sufficient quality to be able to pool the data. Although several trials reported an improvement in survival for patients receiving hydroxyurea, this conclusion was unreliable owing to methodological problems associated with trials including small sample size, a large number of patients excluded from analysis and questionable methods of analysis such as exclusion of treatment related deaths.
13 trials with a total of 9961 participants were included in this review. Ten trials with a total of 8562 participants involved an indacaterol versus placebo comparison. Five trials with a total of 4133 participants involved an indacaterol versus twice-daily beta2-agonist comparison. Two trials included both indacaterol versus placebo and indacaterol versus twice-daily beta2-agonist comparisons. Trials were between 12 and 52 weeks duration and compared doses between 75 mcg and 600 mcg. In most trials, mean forced expiratory volume in 1 second (FEV1) was approximately 50% predicted. 1. Indacaterol is an effective medication for the treatment of patients with stable COPD. It results in improved lung function and quality of life. 2. Indacaterol led to improvements in lung function that were clinically similar to those seen with twice-daily long-acting beta2-agonists. 3. No measurable difference was noted between indacaterol and twice-daily long-acting beta2-agonists with respect to quality of life, but important differences cannot be excluded. 4. No significant difference was observed in the number of participants suffering a serious adverse event or mortality, but the confidence intervals were too wide because very few events could be used to rule out important differences. Overall the quality of the evidence was judged to be high. Indacaterol is an effective treatment for patients with stable COPD; it offers benefits that are clinically similar to those of existing twice-daily preparations within the same class of medication but provides the possible advantage of once-daily dosing.
Prostacyclin may benefit patients with pulmonary hypertension (raised blood pressure in the lungs) in the short term but studies longer in duration are required. Pulmonary hypertension occurs when blood is pumped through arteries in the lungs at an increased pressure. The condition can lead to heart failure and death. Once the diagnosis is made, life expectancy ranges from a few months to a few years. Most current treatments apart from lung transplantation do not improve survival. Over an 8-12 week period prostacyclin improved exercise capacity and some measures of blood flow when given intravenously or via injection to patients with pulmonary hypertension. However, with intravenous administration there can be serious side effects as the drug has to be given continuously via a pump into a catheter placed into a central vein. It is not clear how long the drug continues to confer benefit without serious side effects. Prostacyclin can also be given by mouth, under the skin or through an inhaler. These forms of administration may be safer than intravenous prostacyclin and there is evidence that these may be effective in the short term.
The review includes four clinical trials with 75 people who had tardive dyskinesia as a result of using antipsychotic medicines. The participants were randomised into groups that received either their usual antipsychotic medicine plus a benzodiazepine or their usual antipsychotic plus a placebo (dummy medicine). Improvement in TD symptoms was similar between the treatment groups. Participants were just as likely to leave the studies early from the placebo groups as the benzodiazepine groups. Data were not available for outcomes important to patients such as improvement in social confidence, social inclusion, social networks or quality of life. Evidence is limited because the trials are so few, small, and poorly reported. It is uncertain whether benzodiazepines are helpful in the treatment of tardive dyskinesia. The use of benzodiazepines for treating people with antipsychotic-induced TD therefore remains experimental, and because they are highly addictive, a last resort. The low number of studies in this review strongly indicates that this is not an active area of research. To fully investigate whether benzodiazepines have any positive effects for people with tardive dyskinesia, there would have to be more well-designed, conducted and reported trials. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (mcpin.org/).
We included 23 studies to explore the association between interim PET scan results after one to four cycles of chemotherapy and survival outcomes in adults with HL (all stages). We contacted 10 authors, and six provided us with relevant information and/or data. In 16 included studies, participants received either ABVD chemotherapy or BEACOPP chemotherapy (four studies) only, with or without radiotherapy. In 16 studies, participants underwent an interim PET scan in combination with a computed tomography (CT) (PET-CT), which have higher accuracy in detecting primary and secondary cancers than a PET scan alone. In the remaining seven studies, PET-only was conducted. Twenty-one studies conducted interim PET scans after two cycles (PET2) of chemotherapy. Eight studies did not report enough data on our outcomes or population of interest, so we reported the results from these studies narratively. We combined individual study results in meta-analyses to provide robust evidence for our outcomes of interest overall survival and progression-free survival. No study measured PET-associated adverse events (harms). For overall survival, combined results from nine studies (1802 participants) show that there is probably a large advantage in overall survival for people with a negative interim PET scan compared to people with a positive interim PET scan. For progression-free survival, combined results from 14 studies (2079 participants) show that interim PET-negative people may have an advantage for progression-free survival, compared to interim PET-positive people, but we are uncertain about this result. These are unadjusted results, where interim PET was tested as the only prognostic factor. Eight studies reported adjusted results, where the independent prognostic ability of interim PET was assessed against other established prognostic factors (e.g. disease stage, B symptoms). We could not combine individual study results because the studies did not include identical sets of covariates. Nevertheless, their results indicate a probable independent prognostic ability of interim PET to predict both outcomes. Regarding the unadjusted results, we rated our certainty of the evidence as 'moderate' for overall survival. This means that the true effect is likely to be close to the estimated effect, but there is a possibility that it is substantially different. For progression-free survival, we rated our certainty of the evidence as 'very low', meaning that we have little confidence in the effect estimate, and that the true effect is likely to be substantially different from the estimated effect. Regarding the adjusted results, we rated our certainty of the evidence as 'moderate' for overall survival, and 'low' for progression-free survival. We searched data bases up until 2 April 2019, and one trial registry on 25 January 2019.
This review included randomised controlled trials, (clinical studies where people were randomly assigned into one of two or more treatment groups), that compared the use of saline and heparin to prevent blockage, and other complications related to long term catheters. The evidence is current to April 2015. Two review authors independently reviewed the studies. Three studies with a total of 245 participants were included in the review. The three trials directly compared the use of saline and heparin, however, between studies, all were very different in the way they compared saline and heparin, with different concentrations of heparin and different frequency of flushes reported. We were able to combine the results of two studies; the analysis showed imprecise results for the blocking of catheters and blood stream infections between normal saline and heparin. One study reported the duration of catheter placement to be similar between the two study arms. The overall quality of the evidence ranged from low to very low. There was high risk of bias for blinding, there were differences between the studies methods and interventions, inconsistent results between the studies, and not all studies reported all outcomes of interest. We found there was not enough evidence to determine which solution, heparin or saline, is more effective for reducing complications. Further research is required and is likely to have an important impact in this area.
We included six randomised controlled trials (RCTs), that is, studies in which participants are randomly allocated to one of two or more treatment groups. Five of the studies took place in the USA, and the sixth in Iran. The studies included 438 people with ADHD. All evaluated a long-acting version of bupropion, that is to say, a version of the drug is absorbed slowly, and can therefore be taken just once a day. This simple dosage suits people with ADHD, as the illness may make it difficult for them to remember to take their medication. The duration of the studies varied between six and 10 weeks. All participants were diagnosed with ADHD, and often had other mental health problems. In one study, all participants had ADHD and were addicted to opioids (a drug that relieves pain). Four studies were funded by industry and two studies were publicly funded. In one of the publicly-funded studies, the lead author was paid by industry (although not by the manufacturers of buproprion) for research activities. Bupropion may lead to a small improvement in ADHD and it may also decrease symptoms related to ADHD. The drug does not have more adverse effects than treatment with placebo. Bupropion may be an alternative treatment for adults with ADHD who cannot or will not take stimulant drugs. The quality of the evidence in this review is low, because we found very few studies; five of the six studies were small, and all were poorly conducted. The effect of bupropion on various aspects of daily functioning was not investigated. Also, no studies assessed the long-term effects of this drug. Further studies are needed, to assess whether bupropion is effective in specific ADHD subgroups or in people who have additional disorders.
In total, 28 articles on 24 unique studies met the inclusion criteria. Our results showed that the overall risk of arterial thrombosis was was 1.6-fold increased in women using oral contraceptive pills compared with women who did not use oral contraceptive pills. The risk did not vary clearly according to progestagen type. However, we found that the risk of arterial thrombosis seemed to be twice as high in women taking pills with higher doses of estrogen. Also, the risk of other side effects of oral contraceptive pills (such as a blood clot in a vein-venous thrombosis) should be considered before any type of oral contraceptive pill is prescribed. It is likely that the COC pill containing levonorgestrel and 30 µg of estrogen is the safest oral form of combined oral hormonal contraception. The overall quality of evidence in this review was moderate. Most studies (22 out of 28) correctly confirmed that patients had been diagnosed with arterial thrombosis. However, only four studies also checked that the type of pill a patient had been using was reported correctly. In addition, only half of the studies ensured that the correct comparisons were made between patients with and patients without arterial thrombosis. Also of importance is the fact that the analysis on progestagen type was based on few studies only.
The evidence available was limited to six trials with participants who had not undergone lung transplants (total of 203 adults) and one trial with 34 adults who had undergone lung transplantation. Bisphosphonates consistently increased bone mineral density at the lumbar spine and hip regions. The rates of fractures (vertebral and non-vertebral) or deaths were not reduced by bisphosphonate therapy. However, this may be related to the small numbers of participants involved and the short duration of the trials. Severe bone pain and flu-like symptoms were commonly linked to intravenous bisphosphonates, especially in people not using corticosteroids. More research is needed to assess the effect of pre-treatment with corticosteroids. Additional trials are needed to determine if bone pain is more common or severe (or both) with the stronger drug zoledronate and if corticosteroids lessen or prevent these adverse events. Additional trials are also required to further assess gastrointestinal adverse effects associated with oral bisphosphonates. Trials in larger populations are needed to determine effects on fracture rate and survival.
We included thirteen randomised studies that compared two types of skin grafts or tissue replacements with standard care and four randomised studies that compared two grafts or tissue replacements with each other. In total 1655 patients were randomised in these seventeen trials. Risk of bias was variable among studies. The biggest drawbacks were the lack of blinding (i.e. patients and investigators were aware who was receiving the experimental therapy and who was receiving the standard therapy), industry involvement and the possibility that small studies were less likely to be published if they reported 'negative' results. Adverse advent rates (harm due to the treatment) varied widely. Based on the seventeen studies included in this review, skin grafts and tissue replacements, used in conjunction with standard care, increase the healing rate of foot ulcers and lead to slightly fewer amputations in people with diabetes compared with standard care alone. However, evidence of long term effectiveness is lacking and cost-effectiveness is uncertain. There was not enough evidence for us to be able to recommend a specific type of skin graft or tissue replacement. This plain language summary is up-to-date as of 9 April 2015.
We looked for studies in adults and children attending the emergency department with an asthma attack. We included studies which compared giving inhaled magnesium sulfate, plus standard treatment, with standard treatment alone. We also included studies that compared inhaled magnesium sulfate directly with standard treatment. We included studies carried out anywhere in the world, at any time and written in any language. We found 25 studies in total, which included nearly 3000 people with asthma attacks. This latest update of the review includes several large trials that were carried out to a very high standard. We found that adding inhaled magnesium sulfate to standard treatments may result in small benefits in terms of lung function, hospital admission and severity scores, but we are uncertain about these findings. This is because many of the studies were carried out in different ways and measured different outcomes at different times so it was quite hard to combine the results from individual studies. Inhaled magnesium sulfate did not seem to cause any serious side effects in the studies we found. We did not find evidence that using inhaled magnesium sulfate instead of standard treatment is beneficial. We used a scoring system to rate how confident we are in the findings presented. Our scores ranged from high confidence to very low confidence, but most outcomes we rated as low or very low. This is because we had concerns about the way in which some of the studies were carried out: for example, it was perhaps not clear how people were chosen for the two different treatment groups in the study; or it was unclear whether the patients or people running the trial knew who was getting which treatment. Another factor that reduced our confidence was uncertainty about the combined results: for example in some cases we could not tell whether magnesium sulfate was better, worse or the same. There is some limited evidence that inhaled magnesium sulfate may have a small benefit for people having asthma attacks when added to standard treatment. However, the most recent, high-quality trials did not generally show important benefits. Also, we cannot be sure if some groups may benefit more than other, for example those having more severe attacks.
We searched for studies where people with cystic fibrosis were put into either a group for respiratory muscle training or a control group at random. We included nine studies with 202 people which used a wide variety of training methods and levels. In seven of the studies, the treatment group and the control group each only received either respiratory muscle training or a control treatment (one study had three groups in total: one receiving control treatment and two receiving different levels of training). In one study the participants received both types of treatment, but in a random order. Lastly, one study compared training with usual care. The studies lasted for a maximum of 12 weeks and all were quite small; the largest only had 29 people taking part. The studies included people with a range of ages over six years old, but most seemed to be adults. The studies reported a variety of outcomes. All reported some measure of respiratory muscle strength, and most reported at least one measure of lung function, however only three studies reported on quality of life. Results could not be combined to answer the review question, because the studies either did not publish enough details or did not use the same standard measurements. No study found any difference in lung function after training, but one of the studies reported an improvement in exercise duration when training at 60% of maximal effort and a further study which trained participants at 80% of maximal effort reported some improvements in quality of life judgements. There was some evidence of an improvement in respiratory muscle function in one study. Given this lack of information, a recommendation for or against respiratory muscle training cannot be made. Future studies should look to improve upon the methods of those previously conducted, and should report using standardised measurements. It was generally unclear how people were split into groups for treatment and whether this would have affected the results. Two studies stated that the people assessing the outcomes did not know which treatment those taking part had received, but this was unclear in other studies. Individuals dropped out of three of the studies for reasons which may be directly related to the treatment and therefore may introduce a risk of bias to the results. Other studies did not state how many people dropped out of them. We assessed the quality of the evidence and judged the evidence for lung function, exercise capacity and health-related quality of life to be very low quality, but the evidence for respiratory muscle function to be low quality.
We found two relevant studies to include in the review. Both studies were randomised controlled trials (a type of study in which participants are assigned to one of two or more treatment groups using a random method) in which participants had a diagnosis of UCC. Participants received either an intervention including SLT techniques or 'healthy lifestyle advice' as a control group. We chose to use health-related quality of life and serious adverse events to judge whether SLT is a useful intervention. Only one of the studies comparing SLT to usual care reported data about quality of life (using a questionnaire). After four weeks, participants in the study who were receiving the SLT treatment, physiotherapy and speech and language therapy intervention (PSALTI), had on average an improvement in their quality of life compared to people in the control group. However, this benefit compared to control was short-lived and disappeared after four weeks. This means that although the treatment appeared to work in the shorter term, it may not improve quality of life in the longer term compared to usual care. We also looked for information about side effects or harms of the treatment. The same study reported that no one experienced serious side effects or harms during the study. Other ways of measuring the impact of SLT were also considered, and in each case relevant data were only provided by one study. An improvement in objective cough counts (using a cough monitor), symptoms (using symptom scores), and clinical improvement was shown with SLT compared to controls. The included trials reported no difference for other secondary outcomes such as subjective measures of cough or cough reflex sensitivity (measured in the laboratory using airway irritants). The small number of high-quality, relevant studies found in this review means that we cannot be sure of the overall benefits of SLT in the management of UCC. Improvements in health-related quality of life were associated with the PSALTI intervention over a short period in one study, but further research is required to replicate this finding. Overall, more controlled trials are required to fully examine the potential of SLT for the management of UCC.
Six randomised controlled trials assessing 434 participants were included. The studies appraised four types of chest physiotherapy, namely conventional chest physiotherapy, osteopathic manipulative treatment (including paraspinal inhibition, rib raising, and diaphragmatic or soft myofascial release), active cycle of breathing techniques (including active breathing control, thoracic expansion exercises and forced expiration technique) and positive expiratory pressure. None of these techniques (versus no physiotherapy or placebo therapy) reduce mortality. Among three of the techniques (conventional chest physiotherapy, active cycle of breathing techniques and osteopathic manipulative treatment) there is no evidence to support a better cure rate in comparison with no physiotherapy or placebo therapy. Limited evidence indicates that positive expiratory pressure (versus no physiotherapy) and osteopathic manipulative treatment (versus placebo therapy) can slightly reduce the duration of hospital stay (by 2.02 and 1.4 days, respectively). In addition, positive expiratory pressure (versus no physiotherapy) can slightly reduce the duration of fever by 0.7 day, and osteopathic manipulative treatment (versus placebo therapy) might reduce the duration of antibiotic use by 1.93 days. No severe adverse events were found. In summary, chest physiotherapy should not be recommended as routine additional treatment for pneumonia in adults. The limitation of our review is that six published studies which appear to meet the inclusion criteria are awaiting classification (five of which are published in Russian).
This review included four studies with 442 participants. One study compared myomectomy to no treatment. The remaining three studies compared different surgical methods of performing a myomectomy. The evidence is current to February 2019. One study examined the effect of myomectomy compared to no treatment. Results found insufficient evidence to determine a difference between treatment options for clinical pregnancy rate or miscarriage rate. This study did not report on live birth, preterm delivery, ongoing pregnancy or caesarean section rate. Regarding the best surgical approach, three studies were identified. Two studies compared myomectomy by mini-laparotomy or laparotomy to laparoscopic myomectomy and found insufficient evidence to determine a difference for live birth, preterm delivery, clinical pregnancy, miscarriage, caesarean section and ongoing pregnancy rate. The third study compared use of different surgical equipment during hysteroscopic myomectomy and found insufficient evidence to determine a difference for live birth/ongoing pregnancy rate, clinical pregnancy rate and miscarriage rate. This study did not report on caesarean section or preterm delivery rate. It is clear that more studies are needed before a consensus can be reached on the role of myomectomy for infertility. The evidence was very low quality. There are some concerns regarding how the data were analysed and therefore the evidence cannot be considered to be conclusive until further studies are available.
We searched for evidence from randomised controlled trials on 6 January 2016 and found 10 studies (involving a total of 1354 women). Nine studies (1274 women) compared intravenous antibiotic administration with antibiotic irrigation (washing with a saline solution containing antibiotics). The two routes gave similar results on important outcomes including infection of the uterus/womb (low-quality evidence) and wound infection (very low-quality evidence). The studies did not report on blood infections in the newborn infant (sepsis). The numbers of women who had urinary tract infection (very low-quality evidence), serious infectious complications (very low-quality evidence) or fever after birth (very low-quality evidence) also did not clearly differ between groups. There was no clear difference between groups in terms of how long women spent in hospital and no data reported on the number of women who were readmitted to hospital. No women had allergic reactions to the antibiotics (very low-quality evidence) in the three studies that reported this outcome. None of the studies reported information about whether the babies had any immediate adverse reactions to the antibiotics. One study (involving 80 women) compared intravenous antibiotics with taking antibiotics orally but it did not report on any of this review's outcomes. The studies included in this review did not clearly report how they were carried out and outcome data were incomplete. Too few women were included in each study for sufficient numbers of events to see a clear difference in outcomes between the two groups of women. This meant the evidence was of low quality. Therefore, we need to exercise caution in the interpretation and generalisability of the results. High-quality studies are needed to determine the safest, most effective way of giving preventive antibiotics. Such studies should evaluate more recently available antibiotics and consider potential side effects that the intervention may have for the baby.
Through April 2014, we did computer searches for studies of birth control methods containing hormones and risk of fractures. Outcomes could also be bone mineral density or markers of bone changes. Birth control pills included types with both estrogen and progestin. Also included were implants and injectables with only progestin. We wrote to researchers to find other trials. We included randomized trials in any language that had at least three treatment cycles. The studies had to compare two types of birth control or one type of birth control or a supplement with a placebo or 'dummy' method. We found 19 trials. Fifteen studies compared one birth control method with another hormone method. Two trials used a placebo or 'dummy.' One compared a hormone method to a method without hormones. None had fractures as an outcome and most looked at bone density. Birth control methods with both estrogen and progestin did not appear to affect bone health. However, 'depo,' which is injected and has only progestin, was related to lower bone density. The two depo trials with placebos showed increased bone density when some estrogen was given to women on depo. Bone density decreased in women who got a 'dummy' with the depo. Whether this decrease is important to the woman's health is not known. For implants, an etonogestrel implant with one rod showed a greater decrease in bone density than a two-rod levonorgestrel implant. However, other implants studied did not show the same pattern. The studies had data of moderate quality. Whether hormonal contraceptives affect fracture risk cannot be judged from current information. These contraceptive methods work well for birth control. Health-care providers and women should think about the costs and benefits. For instance, injectable use can occur without a partner's knowledge, and is simpler than taking pills every day. Also, progestin-only methods are suggested for some women with health problems who should avoid estrogen.
This review contains evidence up to July 2017. We found 15 studies which together included more than 30,000 people at high risk of heart disease who are taking aspirin. All studies randomly assigned participants to the intervention group (taking aspirin and clopidogrel) or the control group (taking aspirin and placebo (a pretend treatment that has no effect). Participants took clopidogrel between six weeks and 3.4 years, depending on the study they took part in. The results do not apply to people with recent placement of coronary stents (tubes inserted in the blood vessel to keep it open), who were excluded from this review. The results showed that there is a benefit of adding clopidogrel to aspirin in terms of reducing the risk of heart attack or stroke. However, there is a higher risk of major and minor bleeding associated with this. There was no effect on death due to heart problems or death from any cause. Using Cochrane criteria, four trials were at low risk of bias. Using GRADE standards, the quality of published evidence was moderate for most results, but low for death from any cause and very low for side effects.
Yet, many physicians initiate combination therapy in patients with asthma, without a prior trial of inhaled corticosteroids alone. The purpose of this review was to compare the benefit and safety profile of initiating treatment with the combination of ICS and LABA as compared to a (1) similar and (2) higher dose of ICS alone in asthmatic patients who had not received ICS previously. This review identified 28 randomised controlled trials. The combination of ICS and LABA did not reduce the risk of patients with exacerbations requiring rescue oral corticosteroids but improved lung function, symptoms and minimally reduced the use of rescue ß2-agonists as compared to a similar dose of ICS alone. Initiating ICS at a higher dose than that used with LABA in the control group significantly reduced the risk of exacerbations and study withdrawals over that observed with the combination of LABA and a lower dose of ICS; there is insufficient evidence to comment on the impact on lung function, symptoms and use of rescue ß2-agonists. The current evidence does not support use of combination therapy with LABA and ICS as first line treatment in adults and children with asthma, without a prior trial of inhaled corticosteroids.
We reviewed the effects of dehydroepiandrosterone (DHEA)/testosterone as an adjunctive therapy to standard antipsychotic drugs for people with schizophrenia and found three relevant small, short studies. All trials compared antipsychotic drugs plus DHEA with antipsychotic drugs and placebo. Results are inconclusive, with most outcomes being either non-significant or contradictory and a much larger, conclusive study should be undertaken. Currently however, people with schizophrenia should only agree to take this experimental treatment within the context of a well designed experimental study. We found nothing in these studies to suggest that it should be used in routine care.
This methodology review was conducted to assess the effects of different methods for obtaining unpublished studies (data) and missing data from studies to be included in systematic reviews. Six studies met the inclusion criteria, two were randomised studies and four were observational comparative studies evaluating different methods for obtaining missing data. Five studies assessed methods for obtaining missing data (i.e. data available to the original researchers but not reported in the published study). Two studies found that correspondence with study authors by e-mail resulted in the greatest response rate with the fewest attempts and shortest time to respond. The difference between the effect of a single request for missing information (by e-mail or surface mail) versus a multistage approach (pre-notification, request for missing information and active follow-up) was not significant for response rate and completeness of information retrieved (one study). Requests for clarification of methods (one study) resulted in a greater response than requests for missing data. A well-known signatory had no significant effect on the likelihood of authors responding to a request for unpublished information (one study). One study assessed the number of attempts made to obtain missing data and found that the number of items requested did not influence the probability of response. In addition, multiple attempts using the same methods did not increase the likelihood of response. One study assessed methods to obtain unpublished studies (i.e. data for studies that have never been published). Identifying unpublished studies ahead of time and then asking the drug industry to provide further specific detail proved to be more fruitful than sending of a non-specific request. Those carrying out systematic reviews should continue to contact authors for missing data, recognising that this might not always be successful, particularly for older studies. Contacting authors by e-mail results in the greatest response rate with the fewest number of attempts and the shortest time to respond.
This review found only two randomized trials enrolling a total of 268 patients. One trial compared standard oxygen recompression to helium and oxygen recompression, while the other compared oxygen recompression alone to recompression and an adjunctive non-steroidal anti-inflammatory drug (NSAID). Both trials suggested that these additional interventions may shorten the course of recompression required. For example, the use of an NSAID reduced the median number of recompression sessions required from three to two. We conclude that there is little evidence for using one recompression strategy over another in the treatment of decompression illness and that the addition of an anti-inflammatory drug may shorten the course of recompression required. More research is needed.
We found one published randomized controlled trial, including 226 adults. We found moderate-quality evidence of harm (stroke due to bleeding in the brain, and death or dependency) over one year of follow-up from interventional treatments compared to conservative management for adults who had a brain AVM that had never bled. The long-term risks are unknown. Overall, the quality of the evidence was moderate because there was just one trial and it did not use blinding. More information will become available from the three trials that are ongoing.
The review found 10 trials, most of low methodological quality and most funded by a single pharmaceutical company. In addition, trials were small and had few participants thus evidence suggesting atovaquone-proguanil as more effective than a number of single drug treatments at eliminating the Plasmodium falciparum malaria parasite from the blood was limited. There were few good quality data comparing atovaquone-proguanil with other new combination therapies. There were not enough data to assess adverse events, but all trials recorded some adverse events.
seven studies, which involved 7586 women. Our evidence is current to May 2015. Local recurrence was rare, but more common with PBI (low-quality evidence) and the breast appearance (scored by doctors) was worse with PBI (low-quality evidence). Survival did not differ (high-quality evidence). Scarring in the breast was worse with PBI (moderate-quality evidence). The same number of women died of breast cancer with either treatment (moderate-quality evidence). The same number of women developed spread of breast cancer around their body with either treatment (moderate-quality evidence). There appeared to be the same number of women who eventually needed the breast removed (mastectomy) after both treatments. Mastectomy could happen because of cancer regrowth in the breast or bad side effects (low-quality evidence). that at the moment, PBI does not give the same cancer control in the breast as treating the whole breast, but the difference was small. It may cause worse side effects. There are five big ongoing studies that will be important to answer this question. We hope to have a clearer answer in the next update of this review.
The review identified four studies including 141 participants; two of these were in children (aged six months to 14.5 years) and the other two did not specify the age of the participants. The people taking part in the studies received different forms of vitamin E supplements (either water-soluble or fat-soluble), placebo (a substance containing no medication) or no supplements. Three studies stated that the treatment for each person was chosen at random, but one study only said the people were split into different groups. Three of the studies showed an improvement in vitamin E levels after supplementation, but result should be interpreted with caution due to potential risks of bias. No studies reported any disorders related to vitamin E deficiency. As the studies used different forms of supplements and different doses, it was difficult to combine the results and apply them to the wider cystic fibrosis population, but the results did show that vitamin E supplementation can lead to an improvement in vitamin E levels in people with cystic fibrosis and may help avoid problems caused by vitamin E deficiency. Future trials, especially in people already receiving treatment with pancreatic enzymes and vitamin E supplements, should look at more specific outcomes such as vitamin E status, lung function and nutritional status. They could also look at the best level of vitamin E supplements needed to be most clinically effective. We do not think that any of the people taking part in the studies could tell whether they received the supplements or the placebo, so that would not have affected the results; although they would have known if they were taking supplements or not taking anything. We could not tell from the information we have whether most of the studies were designed so all people had an equal chance of being in any of the groups. We also could not tell if anyone would have been able to guess in advance which group they would be in. It was also not clear if there were results reported for everyone taking part in the studies and the reasons why anyone might have dropped out of the studies. We do not know if these facts will affect our confidence in the results.
Two randomised controlled trials from Kenya were included in the review. One trial compared short weekly text messages against standard care. The other trial compared short daily, long daily, short weekly and long weekly messages against standard care. In the trial comparing only short weekly messages to standard care, text messaging was associated with lower risk of non-adherence at 12 months, and with the non-occurrence of virologic failure at 12 months. Combining the data from both trials, weekly mobile phone text-messaging was associated with greater ART adherence at 48-52 weeks. The effect of short weekly text-messaging was also significant. In the trial that compared different intervals and lengths for text-messaging to standard care, long weekly text-messaging was not significantly associated with a lower risk of non-adherence compared to standard care. Patients receiving weekly text-messages of any length were at lower risk of non-adherence at 48 weeks than were patients receiving daily messages of any length. There were no significant differences between weekly text-messaging of any length and between short or long messaging at either interval. Compared to standard care, any daily text-messaging, whether short or long, did not reduce the risk for non-adherence. Weekly mobile phone text messages to patients on ART can help them to take their medication every day. It can also help to reduce the amount of HIV in their bloodstream. Because the two included trials were with adult patients only, there is a need for trials of this intervention with adolescents. Also, as the two trials were conducted in Kenya, a low-income country, there is a need for trials of this intervention in high-income countries.
This systematic review identified two randomised clinical trials with very small numbers of participants. One of the trials was a pilot trial and compared simvastatin with placebo, and the other trial assessed atorvastatin versus fenofibrate versus a combination of the two. The small pilot trial (n = 16 patients) assessing simvastatin versus placebo in NASH patients did not show significant effects on liver enzyme activities or liver histology. No adverse events were reported. The other trial compared atorvastatin versus fenofibrate versus a group receiving both interventions in 186 patients with NAFLD. There were no statistically significant differences between any of the three intervention groups regarding the 54 week mean activities of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, or alkaline phosphatases (liver enzymes) in the blood. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed higher in the fenofibrate group compared with the other two intervention groups. Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity, one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to raised alanine aminotransferase activity, over three times the upper normal limit. Both trials were at high risk of bias (that is, overestimation of benefits and underestimation of harms). Furthermore, the groups were small raising the risks of random errors (that is, play of chance). Accordingly, we did not find evidence to support or refute the use of statins for patients with NAFLD or NASH. Further unbiased trials with larger numbers of patients looking explicitly at patient-related outcomes of interest (for example, quality of life, development of cirrhosis, and mortality) are needed to assess the effects of statins on NAFLD or NASH.
We looked for all studies that compared Aquablation to transurethral resection of the prostate. We included both studies in chance decided how men were treated and studies in which men and their urologist decided. We searched for studies up to 11 February 2019. We found only one study in which chance decided how men were treated. The study compared Aquablation to transurethral resection of the prostate. On average, men were about 66 years old. We did not find any other studies. We found that Aquablation likely improves urinary symptoms similarly to transurethral resection of the prostate and may also lead to similar quality of life. Rates of unwanted serious effects may also be similar but we are very uncertain about this. Men who have Aquablation may have a similar risk of needing a repeat procedure as those having transurethral resection of the prostate but we are very uncertain of this finding. Aquablation may make little to no difference to erectile function but may have fewer issues with ejaculation, but we are very uncertain of both findings. These findings are based on a single study funded by the company that makes the device used for Aquablation. All data were limited to 12 months' follow-up or less and prostate size was less than or equal to 80 mL. Our certainty about the evidence we found ranged from moderate to very low due to shortcomings in how the study was done and small study size. This means that we have either moderate, limited or very little confidence in the results, depending on the outcome.
Originally, two randomised clinical trials were available for this review. Some short-term benefits were documented in promoting adaptive behaviours in people with dementia during and immediately after their participation in the sessions. In this update, two new trials were included and revealed two different forms of applying snoezelen to dementia care. One is a session-based snoezelen programme while the other is a 24-hour integrated snoezelen care programme. Both trials did not show any significant effects on behaviour, interaction, and mood of people with dementia.
The studies looked at adults over 18 years of age and included (amongst others) people who smoked and took oral contraceptives (both possible risk factors). However, studies involving people who were extremely ill or who had compromised immune systems were not included. Studies which looked at the use of antibiotics to manage dry socket were also not included. Prevention It was found that there is some evidence to show that rinsing both before and after tooth extraction with chlorhexidine gluconate rinse (at 0.12% and 0.2% strength) reduced the risk of having a dry socket. Placing chlorhexidine gel (0.2% strength) in the socket of an extracted tooth also reduced the risk of having dry socket. The risk of developing dry socket depends on many factors, some of which are unknown. Your dentist or dental care professional (DCP) should be able to advise you of your own risk status. To illustrate the effectiveness of chlorhexidine treatment as a preventive measure: if the risk of contracting alveolar osteitis (dry socket) was 1% (one in a hundred) then 232 people undergoing tooth extractions would need to be treated to prevent one case of dry socket; if the risk was 5%, then the number needed to be treated to prevent one case of dry socket would be 47; if the risk rises to 30%, the number needed to be treated to prevent one case of dry socket would be 8. In these trials no serious side effects or reactions by patients due to chlorhexidine were reported. However, two serious events associated with the use of chlorhexidine mouthwash for irrigation of dry socket have been reported in the UK. If people have a history of allergies or have had adverse reactions previously to the use of chlorhexidine mouthwashes they should tell their dentist or DCP before using chlorhexidine. They should also tell their dentist or DCP if they experience any unusual symptoms such as rashes, itching or swelling of the lips whilst using chlorhexidine. It is recommended that all members of the dental team prescribing chlorhexidine products are aware of the potential for both minor and serious side effects, are competent to manage a medical emergency associated with anaphylaxis (toxic shock) and warn patients of the potential for adverse events. Treatment There was insufficient evidence to conclude whether any treatments relieved established dry socket or not.
This review examined 35 randomised controlled trials and eight quasi-randomised controlled trials with 7465 participants. Twenty-two trials with 5546 participants were involved in looking at prevention of phlebitis with Aloe vera, and a further 21 trials with 1919 participants were involved in looking at Aloe vera for the treatment of phlebitis. The included trials mainly compared external application of fresh Aloe vera alone or with another non-Aloe vera treatment such as a wet compress of 75% alcohol or 33%, 50% or 75% MgSO4 with no treatment or the same non-Aloe vera treatment. The duration of intervention lasted from one day to 15 days. Most of the included studies were of low methodological quality with concerns for selection bias, attrition bias, reporting bias and publication bias. The incidence of phlebitis at varying degrees of severity as well as the resolution rate and level of improvement of phlebitis were investigated. The available evidence suggests that external application of fresh Aloe vera alone or combined with other non-Aloe vera treatment may be effective for the prevention and treatment of infusion phlebitis resulting from the intravenous therapy. The conclusions should be cautiously interpreted due to the low methodological quality of the included trials.
We searched for relevant research studies up to 20 August 2016. We found 14 studies that analysed the effectiveness of behavioural interventions to promote RPE use. We also located one ongoing study. Studies had been conducted with 2052 farm, healthcare, production line, office and coke oven workers as well as nursing students and people with mixed occupations. We did not find any studies where the researchers conducted and assessed an intervention at the level of a whole organization. What the research says  All included studies compared different education and training interventions to encourage workers to use RPE correctly or more often. We found very low quality evidence that behavioural interventions such as education and training do not increase the number of workers that use RPE or that use RPE correctly. What is the bottom line  We conclude that there is low to very low quality evidence that behavioural interventions do not encourage workers to use RPE correctly or more often. It is likely that our conclusions will change when new studies are published. We need better quality studies that look at the effectiveness of different types of interventions. These interventions should be targeted at both individuals and organisations, to improve effective RPE use. In addition, further studies should consider some of the barriers to the successful use of RPE, such as experience of health risk, types of RPE and the employer's attitude to RPE use.
Evidence is current to January 2017. We found three studies with 196 stroke survivors who had received a diagnosis of anxiety. One study assessed the effect of a relaxation CD used five times a week for one month for participants with a diagnosis of anxiety. Two studies assessed the use of antidepressants in participants who had both anxiety and depression. One study found that participants were less anxious three months after using a relaxation CD when compared with those who were given no therapy. One study reported that participants were less anxious when treated with an antidepressant medicine (paroxetine), or with paroxetine and psychotherapy, than with standard care. This study reported that half of the participants receiving paroxetine experienced side effects that included nausea, vomiting, or dizziness. The third study also reported that participants were less anxious when treated with an antidepressant (buspirone hydrochloride) than with standard care, and only 14% of those receiving buspirone hydrocholoride reported nausea or palpitations. We judged that the quality of this evidence was very low. Studies were few and each included a small number of participants. Studies assessing antidepressants did not include comparison with a placebo drug, and information in both study reports was insufficient to permit assessment of whether other biases had been introduced. The study of relaxation therapy was very small, with loss of two participants who used the CD, and the study recruitment process may have attracted participants who had a positive bias towards psychological therapies. Current evidence is insufficient to guide the treatment of anxiety after stroke. Additional well-conducted randomised trials are needed.
The evidence is current to November 2016. This review included data from 167 participants (mean age ranged from 54 to 72.5 years) in five studies (sample size of the included studies ranged from 19 to 60 participants). Results from our review showed that compared to a control group that did not exercise before lung surgery, people with NSCLC who exercised before lung surgery had 67% less risk of developing a postoperative lung complication. Based on this result, we would expect that out of 100 people with NSCLC who exercise before lung surgery, seven will experience a postoperative lung complication, compared with 22 people with NSCLC who will experience a postoperative lung complication if they do not exercise before lung surgery. Also, compared to the control group, people with NSCLC who exercised before lung surgery had a chest drain for fewer days (three days less), had a shorter length of hospital stay (four days less), and better 6-minute walk distance (18 metres more), and lung function before surgery (3% better). The overall quality of evidence was low for all of the outcomes, mainly because of the small number of studies found, the small number of participants in the included studies, and limitations in the studies' methods.
We found 19 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) evaluating mainly women receiving different doses of fluoxetine. A total of 1280 overweight or obese participants received fluoxetine and 936 participants received mainly placebo or another anti-obesity medication. The participants in the included studies were followed up for periods varying between three weeks and one year. For our main comparison group — fluoxetine compared with placebo — and for all fluoxetine doses there was a 2.7 kg weight loss in favour of fluoxetine. We are uncertain, however, if an additional study would again show a benefit for fluoxetine. A total of 399 out of 627 participants (63.6%) receiving fluoxetine compared with 352 out of 626 participants (56.2%) receiving placebo experienced a side effect. Dizziness, drowsiness, fatigue, insomnia and nausea were observed approximately twice as often after fluoxetine compared to placebo. A total of 15 out of 197 participants (7.6%) receiving fluoxetine compared with 12 out of 196 participants (6.1%) receiving placebo experienced depression. The studies did not report on death from any cause, health-related quality of life and socioeconomic effects. This evidence is up to date as of December 2018. The overall certainty of the evidence was low or very low, mainly because of the small number of studies per outcome measurement and the small number of participants.
We found 22 studies with 7711 participants. These studies were published from 1971 to 2017. In these studies, chance decided whether people received an antibiotic or a placebo/no treatment. The evidence is current to 4 February 2019. Antibiotics given for UTI prevention before cystoscopy may have had little or no effect on the risk of developing a more serious infection that went into the bloodstream. They may have reduced the risk of infection when both serious infection that went into the bloodstream and infections limited to the bladder were taken together. None of the people included in the trials had serious unwanted effects. Therefore, we concluded that antibiotics given for prevention of UTIs may not cause serious unwanted effects but we are very uncertain of this finding. Antibiotics may also have had little or no effect on minor unwanted effects. They may also have had little or no effect on infections limited to the bladder taken alone, but we were very uncertain of this finding. People treated with antibiotics may have been more likely to have bacteria that were more resistant to antibiotics, but we are very uncertain of this finding. We rated the quality of the evidence as low or very low meaning that our confidence in the results was limited or very limited. The true effect of antibiotics for prevention of UTIs before cystoscopy may be quite different from what this review found.
We searched for studies of smokers treated with medicine to help them quit. We looked at people's genes and at how well their bodies could process nicotine, as this might help us to identify people more likely to quit successfully. We found 33 studies relevant to our review, and we were able to get enough information for 18 clinical trials, including over 9000 smokers, that looked at different medicines used to help people to stop smoking. The results suggest that smokers with specific genotypes may be more likely to be successful quitting smoking with the use of nicotine replacement therapies compared with smokers who do not have those specific genotypes. Smokers whose bodies process nicotine more slowly may also benefit more from nicotine replacement therapy. We did not see effects of genes on the effectiveness of medicines other than nicotine replacement therapy. These results should be interpreted with caution because the included studies did not assign treatments to smokers on the basis of genotype or the rate at which they process nicotine, and because a small number of clinical trials were included in some comparisons.
Three trials examined the use of the drug alendronate to improve BMD in patients with HIV. These three studies were quite different from each other in terms of the populations studied and the interventions used, but even similar studies did not always have heterogeneity. A fourth study examined the use of testosterone in male patients with HIV and AIDS wasting syndrome. The four studies in this review were limited by the fact they were all very small and lasted a short amount of time, and thus they were unable to detect prevention of fractures or changes in number of patients with osteoporosis. There were also further compromises in study design. However, the limited available data show that there may be safe and perhaps effective treatments in the form of alendronate for patients with HIV who have decreased bone mineral density and, in those with AIDS wasting syndrome, testosterone. Larger studies further examining the issue of decreased BMD are currently underway.
The aim of this review was to compare the effect of pre-hospital and in-hospital administration of thrombolytic therapy on all-cause death and disability in individuals having a heart attack. We carried out a comprehensive search for all trials that have investigated this outcome. Two authors worked independently to ensure we found all of the trials and obtained the relevant information from them. Overall, we found three trials with 538 participants which could be included in this review. We found low-quality evidence indicating uncertainty whether the numbers of people dying were different when therapy was given before hospital compared to in hospital (3 trials). We found high-quality evidence that giving therapy before hospital reduced the time taken for an individual to receive thrombolytic therapy by more than 30 minutes (two studies) and generally low-quality evidence that side effects, such as allergic reactions and bleeding, were similar whether therapy was given pre-hospital or in hospital. The main limitations of the evidence were the unclear/high risk of bias in the studies and the low numbers of people recruited. We conclude that clot-busting therapy given before arriving at a hospital reduces the time taken for an individual to receive thrombolytic treatment. The limitations of the evidence we have found should be considered carefully, especially in settings where thrombolysis can be safely and correctly administered by trained staff. We found that there were no trials evaluating pre-hospital thrombolytic therapy in poorer countries, and therefore further research in such settings will provide more information to advise on whether giving this therapy for heart attacks is safe and effective.
Randomised controlled trials (RCTs) comparing either two types of antibiotic therapy or an antibiotic versus a placebo in children with pneumonia. We identified seven studies (1912 children). Within each study, there were some children who hadM. pneumoniaebut we could not extract relevant data relating to efficacy or adverse events relating only to children withM. pneumoniae. Overall the quality of the evidence for each of the main outcomes is very low as there are insufficient data for any outcome. Hence, currently, there is insufficient evidence to show conclusively that antibiotics are effective in children with LRTI caused byM. pneumoniae.
This review includes six small randomised controlled trials that compared ACI with either mosaicplasty or microfracture. Although there are some promising results for ACI compared with microfracture from one trial, the evidence from two other trials testing the same comparison did not confirm these. None of the other three trials testing different comparisons provided conclusive evidence in favour of ACI, although the longer-term results suggest that the results for some types of ACI may improve over time. The review identified several ongoing trials that should help to provide evidence to inform on the use of ACI in the future. Meanwhile, there is insufficient evidence to draw conclusions on the use of ACI.
We identified 10 randomised clinical trials which were eligible for our review. Nine randomised clinical trials (467 participants) provided information for one or more measures (outcomes). The main interventions compared included different forms of interferon (protein secreted in response to viral infection), namely, interferon-alpha alone, interferon-beta alone, pegylated interferon-alpha alone, pegylated interferon-alpha plus ribavirin (another antiviral drug), a vaccine called MTH-68/B made from a different virus, versus no intervention. None of the trials compared direct-acting antivirals (the latest option for treating HCV infection) versus placebo or other interventions. The average follow-up period in the trials ranged from six months to three years. Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. All the trials were at high risk of bias, and the overall quality of the evidence was very low. This means that there is a possibility of making wrong conclusions overestimating benefits or underestimating harms of one intervention or the other because of the way that the trials were conducted. No deaths occurred less than one year after treatment in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials in which participants were followed up beyond one year, there were no further deaths. The number of serious complications was higher with pegylated interferon-alpha plus ribavirin than with pegylated interferon-alpha. The percentage of people with any complications was higher with interferon-alpha and interferon-beta than with no intervention. None of the trials reported health-related quality of life, liver transplantation, liver failure, severe liver damage, or liver cancer. The percentage of people in whom the virus remained in the blood six months after the end of treatment was lower in the interferon-alpha than in the no intervention groups. There was no evidence of differences between the groups for all the remaining comparisons. There is significant uncertainty about the size and direction of the results and high quality randomised clinical trials are required.
Three studies with 84 participants compared a surgical operation to bypass the blockage with the placement of a duodenal stent to bridge the blockage. The evidence is current to May 2018. All studies found that people were able to eat and drink sooner following the placement of a duodenal stent and were subsequently discharged from hospital quicker. The return of symptoms was more likely after a stent and people required further treatment to again restore the ability to eat and drink. There was a higher number of immediate problems in the participants undergoing gastrojejunostomy, including wound and chest infections. In some of the participants who had a stent, subsequent blockage of the stent occurred that required a repeat procedure. The studies included only a small number of participants and all studies were used slightly different methods, making it difficult to be certain of the key results.
This review of clinical trials covered 58 studies in which nurses delivered a stop-smoking intervention to smokers. More than 20,000 participants were included in the main analysis, including hospitalized adults and adults in the general community. The most recent search was conducted in January 2017. All studies reported whether or not participants had quit smoking at six months or longer. This review found moderate-quality evidence that advice and support from nurses could increase people's success in quitting smoking, whether in hospitals or in community settings. Eleven studies compared different nurse-delivered interventions and did not find that adding more components changed the effect. The quality of evidence was moderate, meaning that further research may change our confidence in the result. This is because results were not consistent across all of the studies, and in some cases there were not very many studies contributing to comparisons.
We searched for trials, both published and unpublished, up to October 2012. We included fifteen trials which included 5540 participants and compared opioids against a placebo (fake medication) or other drugs that have been used for LBP. Most people included in the trials were aged 40 to 50 years and all reported at least moderate pain across the low-back area. The trials included a slightly higher proportion of women. Most of the trials followed the patients during three months and were supported by the pharmaceutical industry. In general, people that received opioids reported more pain relief and had less difficulty performing their daily activities in the short-term than those who received a placebo. However, there is little data about the benefits of opioids based on objective measures of physical functioning. We have no information from randomized controlled trials supporting the efficacy and safety of opioids used for more than four months. Furthermore, the current literature does not support that opioids are more effective than other groups of analgesics for LBP such as anti-inflammatories or antidepressants. This review partially supports the effectiveness of several opioids for CLBP relief and function in the short-term. However, the effectiveness of prescribing of these medications for long-term use is unknown and should take into consideration the potential for serious adverse effects, complications, and increased risk of misuse, abuse, addiction, overdose, and deaths. As expected, side effects are more common with opioids but non-life-threatening with short-term use. Insufficient data prevented making conclusions about the side-effect profile of opioids versus other type of analgesics (for example, antidepressants or anti-inflammatories). The quality of evidence in this review ranged between "very low" and "moderate". The review results should be interpreted with caution and may not be appropriate in all clinical settings. High quality randomized trials are needed to address the long-term (months to years) risks and benefits of opioid use in CLBP, their relative effectiveness compared with other treatments, and to better understand which people may benefit most from this type of intervention.
We found four small studies that compared nerve-sparing radical hysterectomy versus standard radical hysterectomy. None of the included studies reported data on overall survival and rate of intermittent self-catheterisation (procedure in which patient periodically inserts a small tube (catheter) through the urethra into the bladder to empty it of urine) over one month following surgery. We could not assess the relative effect of these two operations on quality of life due to inconsistent data reported. Women undergoing nerve-sparing radical hysterectomy had better voiding (a technique of bladder training in which the woman is instructed to urinate according to pre-determined schedules) functions following surgery than those undergoing standard radical hysterectomy. We found no evidence that women undergoing nerve-sparing radical hysterectomy were more likely to have adverse consequences of surgery or relapse of their cancer. The certainty of the evidence is therefore low or very low. Nerve-sparing radical hysterectomy may reduce the chance of bladder dysfunction compared to standard radical hysterectomy. However, the certainty of this evidence is low and further studies have the potential to better inform this outcome. We are very uncertain as to whether nerve-sparing radical hysterectomy is safe in terms of cancer survival outcomes. The evidence of cancer recurrence was of very low-certainty, there were no long term data available regarding risk of death from cancer or other causes. High-quality international studies involving many women would be needed to tell us whether nerve-sparing radical hysterectomy is beneficial in terms of survival for women with early stage cervical cancer, since risk of recurrence in this group are low.
The evidence is current to December 2016. We included five clinical trials with 1799 participants aged 16 to 77 years. The included studies had different treatment periods of 12 to 14 weeks. All five trials were randomized controlled trials, which means that people were randomly divided into groups and compared. This review found that eslicarbazepine acetate was effective when used in combination with other medicines to reduce the number of seizures in drug-resistant focal epilepsy. People who took eslicarbazepine acetate were more likely to have no seizures than people who took the placebo (a pretend tablet), but they were more likely to withdraw from eslicarbazepine acetate treatment because of side effects. Side effects associated with eslicarbazepine acetate were dizziness, nausea (feeling sick), somnolence (feeling sleepy), vomiting (being sick) and diplopia (having double vision). Altogether the five trials used good methods, but information was missing from the trials for between 10% and 45% of people taking each medicine in each trial. This missing information may have introduced uncertainty into results so the evidence in this review is of moderate quality. More research is needed to look at the long-term effects of eslicarbazepine acetate and to explore how well it works in children with epilepsy.
Our search strategy was up to date as of March 2013. We found four trials looking at four different types of tools to help improve the amount of tumour that is removed. The tumour that they looked at was usually high grade glioma but one study also included patients with low grade glioma. Imaging interventions used during surgery included magnetic resonance imaging (iMRI) during surgery to assess the amount of remaining tumour, or a fluorescent dye (5-aminolevulinic acid (5-ALA)) to mark out the tumour. Two trials used pre-operative imaging to map out the location of a tumour, which was then used at the time of surgery to guide the resection (neuronavigation). All the studies were at significant risk of bias and some were small and stopped early. Others were funded by the manufacturers of the image guidance tool involved. We found low quality evidence that using image guided surgery can lead to more of the tumour being removed surgically in some people. It has not been proven that any of the techniques that were evaluated improve overall survival. Data about how each technique can affect a patient's quality of life was poorly reported. The side effects of each technique were also poorly reported, but they did not appear to be more common with image guided surgery. There is a concern that taking out more of the tumour using 5-ALA can lead to patients having a type of stroke early after surgery but long-term the risk seems to be no different between techniques. There was very low quality evidence for neuronavigation and no trials were identified for ultrasound guidance. Evidence for image guided surgery in removing brain tumours is sparse and of low quality. Further research is needed to assess two main questions. 1. Is removing more of the tumour better for the patient in the long-term? 2. What are the risks of making a patient symptomatically worse by taking out more of the tumour, and how may this affect a patient's quality of life?
We searched for studies published up to July 2017. We found only two studies that reported the effects of parent communication training; one study took place at an intervention centre in Canada, the other in South Korea. The studies involved 38 children (20 boys, 18 girls), aged 15 to 96 months, and their mothers. Both studies compared parent communication training with no intervention for communication problems. Mothers attended eight group training sessions 11 to 12 weeks with two or three home visits. The studies involved children with a range of developmental difficulties; most had intellectual disability, 10 had movement disorders (cerebral palsy). However, the extent to which children's movement disorder affected their communication was not clear; all children appeared to have good use of their hands for gesture and pointing, and impairment of speech was not reported. Results were assessed immediately after training. We found no report of results at a later date (longer-term follow-up). In the two small studies, it appears that mothers may have responded more frequently to their child's interaction following parent-mediated communication training. However, there was no associated reduction in mothers' directiveness (such as their use of commands) in conversation and no change in maternal stress. For the children, we found no evidence for change in children's initiation of conversation or of joint attention in interaction with others. Studies did not report any negative effects of training, mothers' adherence to guidance within the training or the acceptability of the programmes. We were not able to evaluate the effects of parent-mediated communication intervention and frequency of children's communication, their use of spoken language in conversation with their parents, their speech production or their language development because the data were not available. We have no reports of children's development of individual communication skills, such as learning to ask questions, and no reports of defects of the intervention on their generic participation or harms arising from the intervention. Finally, we found no reports of maternal satisfaction with the treatment. We judged the evidence from the included studies to be of very low quality because of issues with study design and a lack of detail in the results presented, and because it was not clear whether children's movement disorders affected their communication. Research with larger numbers of families of children whose movement disorders affect their speech and gesture is needed, to test whether communication training for parents can help them to promote the communication development of their young children with movement disorders.
The evidence is current to November 2015. We found two small studies involving 116 children that met our inclusion criteria. Both studies gave children a combination of omega-3 and omega-6 capsules as the intervention for three months. Most of these studies involved boys between 10 and 18 years of age - one was conducted in a school setting, and the other at a specialised clinic. One of the studies was funded by the company that supplied the omega-3 and omega-6 supplements. Another study could not be included in this review because investigators added carnosine (an amino acid that is highly concentrated in the brain) to the PUFAs. Carnosine and PUFAs might have similar effects, so it would not be possible to separate the effects of the two ingredients. Review authors excluded five studies because it was not confirmed that a specific learning disorder was diagnosed in these children. None of the included studies reported effects of PUFAs on reading, writing, spelling or mathematical abilities of children. Evidence of low quality (because studies included few participants and showed evidence of bias) suggests that using PUFAs did not increase the risk of minor disturbances to the digestive system. Included studies reported no other types of adverse effects. Both studies reported on ADHD-related behaviour. However, the format of available data did not allow us to readily combine them or to reach any conclusions. Included studies reported no other secondary outcomes. Evidence is not sufficient to support or refute the use of PUFAs in children with specific learning disorders.
We searched differing databases of published research for all papers relating to the accuracy of IQCODE for selecting those with dementia. We found eleven studies that tested diagnostic accuracy of IQCODE in community dwelling individuals, we were able to combine their findings to give a summary result. We compared two forms of IQCODE questionnaire and found that a short form with fewer questions was just as accurate as the original longer questionnaire. The overall accuracy of IQCODE was reasonable although not perfect. If IQCODE were to be used on its own for assessing large populations of older adults, it would label many people with dementia who do not have the disease and also miss the diagnosis in a substantial proportion.
Meta-analysis is a statistical technique to combine results from separate research studies. A meta-analysis can be performed using summary data published in a study report, referred to as aggregate data (AD), or using data collected on each individual participant in the study, referred to as individual participant data (IPD). A meta-analysis of individual participant data (IPD-MA) can take longer and be more expensive than a meta-analysis of aggregate data (AD-MA), but the IPD-MA can be more reliable and can answer much more detailed questions than an AD-MA. We searched for studies, published up to 7 January 2016, that compared results of IPD-MA with AD-MA. We found that four times out of five, similar conclusions can be drawn, but in one out of five cases the two different types of meta-analyses gave different results and conclusions. As we could not reliably identify when an IPD-MA and AD-MA will differ most using these studies, we recommend that an AD-MA should be done first before doing an IPD-MA. If there are shortcomings with the AD-MA, researchers should then consider the possible benefits of IPD whilst remembering the extra work involved.
We searched medical databases for well-designed studies that compared a group of adults with depression who received additional help with their depression medicines from their pharmacy with a group of adults with depression who received their treatment as usual. The evidence is current to 14 December 2018. We found 12 studies with over 2000 adults taking part. They compared pharmacy-based support with treatment as usual, for example, basic information about their medicines or signposting to other services only. We found that additional support given by the pharmacist was no better at reducing people's depression than their treatment as usual. The studies also showed that people may have liked both approaches the same, although we are uncertain about the results as the evidence was of low certainty. The studies did show that people who received support from their pharmacy were more likely to take their antidepressants as prescribed. We were not able to combine information from the included studies on other outcomes we were interested in (diagnosis of depression, frequency of healthcare appointments, quality of life, social functioning, or side effects). We found no difference in effectiveness when people with depression received additional support from a pharmacist compared with treatment as usual.
This review found evidence that giving all preterm infants (especially very preterm infants) indomethacin on the first day after birth reduced their risk of developing a PDA and the complications associated with PDA (including brain damage due to bleeding into the brain). However, despite these short term effects, the trials found evidence that indomethacin does not increase survival or reduce disability in the longer term.
Four trials have compared pramipexole with placebo in 669 patients with later Parkinson's disease. Two studies were medium term (24 weeks) and 2 studies were short term (4 weeks). Pramipexole significantly reduced the time patients spent in the immobile off state compared with placebo by an average of 1.8 hours. No changes occurred in a dyskinesia rating scale in any of the studies, but dyskinesia recorded as a side effect was reported more frequently with pramipexole. A significant improvement occurred in the Unified Parkinson's Disease Rating Scale (UPDRS) complication score in 2 studies but not in the remaining trials. Significant improvements in UPDRS activities of daily living score occurred with pramipexole in all studies. Significant improvements in UPDRS motor scores in the mobile on state were reported in 3 of the 4 studies. Levodopa dose reduction was allowed in 3 studies and meta-analysis showed a significant difference in favour of pramipexole. There was a suggestion of more side effects such as nausea, vomiting and dizziness with pramipexole and a definite increase in hallucinations in those given pramipexole. There were significantly fewer withdrawals from pramipexole. In conclusion, pramipexole can be used to reduce off time, improve motor impairments and disability and reduce levodopa dose at the expense of increased dyskinetic side effects. This is based on short and medium term trials (up to 24 weeks). Further trials are required to directly compare the newer with the older dopamine agonists.
This review ​considered evidence that was up to date at 31 December 2014. We found eight relevant trials with 365 participants. These trials involved children and adults whose decay lesions (tooth decay) were randomly assigned to different micro-invasive and non-invasive treatments. There were no studies comparing micro-invasive interventions with invasive treatment (fillings). Four studies received financial support from intervention inventors or manufacturers to carry out the research. The current evidence shows that micro-invasive treatments can significantly reduce the likelihood of dental decay progression compared with the described non-invasive methods. There are too few studies to decide which micro-invasive treatment technique is best or the impact of different clinical and patient considerations. No negative side effects were reported; however, only half of the studies measured this outcome and the follow-up time of some of the studies was relatively short. Although further research could possibly change our findings, the available evidence gives us moderate confidence that micro-invasive treatments are much more effective than non-invasive treatments for stopping tooth decay.
This review compares the effectiveness of three inhaled steroids. Fluticasone (FP) was compared with either beclomethasone (BDP) or budesonide (BUD) for treating people with chronic asthma. When FP was given to children or adults at approximately half the daily dose of either BDP or BUD, it appeared to be at least as effective as the other two drugs in improving airway opening. There was not enough information available to draw conclusions concerning the effect of these drugs on symptoms, or the risk of an acute asthma exacerbation. When given at the same dose as BDP or BUD, FP treated participants had slightly better lung function. However, at the same dose FP was also associated with increased hoarseness, although it did not lead to increased incidences of other side-effects associated with steroids such as oral thrush or sore throat.
For participants needing additional pain relief, combined analysis of opioids (pentazocine and morphine) showed a significant benefit when compared with non-opioid treatments. Two trials showed that buprenorphine and pentazocine were each more effective than procaine. Our confidence in the stability of these effects is low, however, due to limitations in the number of studies and participants, and the low quality of the way the trials were run and reported. No serious or life-threatening adverse events were linked to the drugs being studied. One death was reported, in a procaine group, across all the included trials. On the evidence so far, opioids may be an appropriate treatment option and might have the advantage of decreasing the need for additional pain relief. We found no clear difference in the risk of pancreatitis complications or serious adverse event between opioids and other pain relief treatments. However, the findings of this review are limited by the lack of information to allow full appraisal of the risk of bias, the measurement of relevant outcomes and the small numbers of participants covered by the trials.
The findings of this review indicate that professional advice and guidance with continued support can encourage people to be more physically active in the short to mid-term. More research is needed to establish which methods of exercise promotion work best in the long-term to encourage specific groups of people to be more physically active.
This review involved the assessment of different inhaler devices for delivery of inhaled bronchodilators in stable chronic obstructive pulmonary disease (COPD). Studies included in this review involved pressurised metered dose inhalers (pMDI) being compared to any other handheld inhaler device containing bronchodilators. Only three randomised controlled trials met the inclusion criteria. Due to the very small number of studies included in this review, it is not possible to draw any conclusions on the use of inhaler devices containing bronchodilators in COPD. There need to be further well designed randomised controlled trials examining the role of bronchodilators in COPD.
We identified randomized controlled trials that compared oral immunotherapy to placebo or continued avoidance diet in children and adults with cow's milk allergy. Five studies satisfied our inclusion criteria. In total there were 196 participants (106 in the treatment group and 90 in the control), all of whom were children. In general, the quality of the studies was low. Because the trials involved small numbers and there were problems with the way they were done, further research is needed. The current evidence shows that oral immunotherapy can help a majority of allergic children tolerate a full serving of milk, as long as they continue drinking this amount each day. However, it is not known if this protection is continued if the immunotherapy is stopped for some time. Side effects during oral immunotherapy are frequent and most patients will have at least some mild symptoms. In the studies we included, for every 11 patients who received oral immunotherapy, one needed to be treated with epinephrine injection at some point for a serious allergic reaction to the therapy.
The review found some evidence that glycerol improves the short term survival after stroke, but there was not enough evidence to decide whether glycerol helps avoid disability after stroke. Adverse effects of glycerol treatment did not happen often, but a small number of treated patients were found to have blood in their urine (this disappeared after the glycerol treatment was stopped). More research is needed.
The researchers found twenty-seven studies (1,011 participants) that fulfilled the search criteria. Eleven of these studies, which included 378 patients, compared elemental to non-elemental diets at producing remission in Crohn's disease. Eight studies, which included 352 patients, investigated enteral nutrition compared to steroid therapy at inducing remission in Crohn's disease. The researchers searched the medical literature extensively up to July 5, 2017. Very low quality evidence suggests that steroids may be more effective than enteral nutrition for induction of remission in adults with active Crohn's disease. Very low quality evidence also suggests that enteral nutrition may be more effective than steroids for induction of remission in children with active Crohn's disease. There was no difference in remission rates between elemental and non-elemental diets. An increase in side effects was not seen with elemental diets compared to non-elemental diets, nor with enteral nutrition compared to steroids. Common side effects experienced with enteral nutrition included vomiting, diarrhea, heartburn and flatulence . Common side effects associated with steroid use included acne, moon facies, muscle weakness, hyperglycemia (high blood sugar) and hypoglycemia (low blood sugar) . Patients on enteral nutrition were more likely to withdraw from the study due to side effects than those on steroids. The most common reason for study withdrawal was inability to tolerate the taste of the enteral nutrition diet. Enteral nutrition should be considered in pediatric Crohn's patients or in adult patients who can comply with nasogastric tube feeding or perceive the formulations to be palatable, or when steroid side effects are not tolerated or better avoided. Further research is required to confirm the superiority of corticosteroids over EN in adults. Further research is required to confirm the benefit of EN in children. More effort from industry should be taken to develop palatable polymeric formulations that can be delivered without use of a nasogastric tube as this may lead to increased patient compliance with this therapy.
Our review included six randomised control trials (RCTs) that involved 544 participants. Five RCTs compared FAE with placebo, and one compared FAE with methotrexate. The outcomes we were interested in measuring were the Psoriasis Area and Severity Index (PASI), which is a psoriasis severity score, and the proportion of participants who discontinued treatment because of adverse (side) effects that are common but sufficiently serious that the drug had to be stopped, such as severe diarrhoea, infections, or cutaneous malignancy. It was difficult to pool and compare results because outcome measures differed between the studies. Three studies reported significant benefit with FAE when compared with placebo after 12 to 16 weeks of treatment, but we could not combine these results in a statistical analysis to show the overall difference. The included studies did not fully examine the chance of discontinuing FAE treatment because of adverse effects, which is uncertain. One study showed that individuals on FAE are nearly five times more likely to develop nuisance adverse effects; the most common were diarrhoea and abdominal cramps, flushing, reversible protein loss in the urine, and raised levels of eosinophil blood cells. Two RCTs were similar enough to allow the combination of their results and found that FAE were better than placebo when measured by the proportion of individuals who experienced at least a 50% improvement in their psoriasis severity score. One study reported improvement of individuals' quality of life with FAE in comparison with placebo, but the significance of this difference could not be calculated. The benefit of FAE was similar to methotrexate after 12 weeks when changes in disease severity from the start to the end of the trial were compared. The number of individuals experiencing nuisance adverse effects with these two treatments was not significantly different. The included studies, which were too small and of limited duration to provide evidence about rare or delayed effects, reported no serious adverse effects of FAE. The risk of study bias, which means any factors that may systematically deviate away from the true findings, was unclear in most studies. This may be because most of the studies were conducted decades ago or were incompletely reported. Several analyses comparing FAE with placebo and methotrexate were limited because the studies were small or did not provide enough information to establish how these treatments compare with each other. Therefore, the overall quality of the evidence was low when comparing FAE with placebo and very low when comparing FAE with methotrexate. Future RCTs should use standard psoriasis outcome measures, including a validated quality of life scale, to enable the comparison and combination of results. They should be longer in duration or have longer follow-up phases to provide evidence about any delayed adverse effects.
We found no new studies in this update. This review includes one previously identified randomised controlled trial performed in 1965. This study involved 2307 healthy people at a training facility for the United States Navy and evaluated the effect of a live weakened (attenuated) adenovirus vaccine compared to a fake vaccine (placebo). This study was funded by a government institution. There were no differences in the frequency of occurrence of the common cold between those who received the vaccine compared to those who received a fake vaccine. There were no adverse events related to the vaccine. However, due to the low numbers of people included in the study and numbers of colds, as well as flaws in the study design, our confidence in the results is low. Further research may be able to clarify if vaccines can prevent common cold, since the current evidence does not support the use of adenovirus vaccine to prevent common cold in healthy people. We assessed the quality of the evidence as low due to high risk of bias and low numbers of people included in the study and numbers of colds, which resulted in imprecision.
This review included four RCTs involving 438 patients that investigated the benefits and harms of routine abdominal drainage post-gastrectomy for gastric cancer. There was no evidence of a difference between the two groups in deaths, post-operative complications, and initiation of a soft diet. The results showed that drains increased harms by prolonging operation time and post-operative hospital stay, and led to drain-related complications without providing any additional benefit for patients with gastric cancer undergoing gastrectomy. There was no convincing evidence to support the routine use of drains after gastrectomy for gastric cancer. The overall quality of the evidence according to the GRADE approach was 'very low' for deaths and re-operations, and 'low' for post-operative complications, operation time, and post-operative length of stay. This review included only four RCTs, and not all of the included studies reported all outcomes that we were assessing. Therefore, the quality was mainly limited by insufficient data.
We searched for studies that randomly compared any treatment versus no treatment, placebo (pretend treatment) or any other intervention. Outcomes were live birth, clinical pregnancy, miscarriage and presence or severity of scar tissue at the second-look procedure. We found 16 studies. Treatments included using a device versus no treatment (two studies; 90 women), hormonal treatment versus no treatment or placebo (two studies; 136 women), device combined with hormonal treatment versus no treatment (one study; 20 women), barrier gel versus no treatment (five studies; 464 women), device with the use of membranes of the afterbirth of newborn babies versus device without membranes (three studies; 190 women), one type of device versus another device (one study; 201 women), gel combined with hormonal treatment and antibiotics versus hormonal treatment with antibiotics (one study; 52 women) or device combined with gel versus device (one study; 120 women). From 1273 randomly assigned women, data on 1133 women were available for analysis. In only two studies, all women had difficulty becoming pregnant. Most studies (14/16) were at high risk of bias for at least one reason. As no study reported live births, we also included data on term delivery or ongoing pregnancy, which five studies reported. It was unclear whether there was a difference between anti-adhesion treatment compared to no treatment (two studies; 107 women) or to other treatment (three studies; 180 women) for increasing the chance of a liveborn baby, a term delivery or an ongoing pregnancy. The use of some anti-adhesion therapies (device with or without hormonal treatment or hormonal treatment or gels) (eight studies; 560 women) may diminish the risk of scar tissue formation compared to no treatment. We would expect that out of 1000 women treated by surgery, between 153 and 365 women would develop scar tissue after using gels, compared with 545 women when no treatment was used. The evidence was current to 6 June 2017. The overall quality of the study evidence ranged from very low to low. There were limitations to the studies, for example, a serious risk of bias related to participants and investigators knowing what treatment was given. More research is needed before anti-adhesion treatment can be offered in everyday clinical practice after surgery of the womb in women having difficulty becoming pregnant.
We searched all databases for relevant studies published between January 1950 and February 2014. We included only one study that enrolled 551 participants and treated one half with methotrexate followed by WBR, and the other half with methotrexate alone. If participants in the latter group did not respond sufficiently to methotrexate alone, another drug, cytarabine, was given. Participants of a minimum of 18 years of age were enrolled at 75 centres in Germany between May 2000 and May 2009. When we analysed the data regarding the effect of chemotherapy plus WBR or chemotherapy alone on overall survival, the results were imprecise and either treatment could have been superior to the other. Another outcome we considered in addition to overall survival was progression-free survival (PFS), a state in which the disease does not get any worse. The addition of radiotherapy to chemotherapy had a positive effect on PFS, slightly extending the period in which the disease did not progress in comparison to that acheived with chemotherapy alone. The authors did not analyse treatment-related mortality.We also looked at whether treatment resulted in any damage to healthy brain tissue during treatment. We found no evidence that treatment-related symptoms of brain function impairment were more common in the group of participants receiving chemotherapy plus radiotherapy than in those receiving chemotherapy alone. We consider the quality of the evidence body as moderate to low, as we included only one trial with a small number of participants. As the included study did not analyse adverse events in all participants, we consider the quality of the evidence for the outcome of neurotoxicity as very low. In summary, the currently available evidence (one randomised controlled trial) is not sufficient to conclude that WBR plus chemotherapy and chemotherapy alone have similar effects on overall survival in people with PCNSL. The addition of WBR to chemotherapy may increase progression-free survival, but could possibly also increase levels of toxic effects on the brain. Further prospective randomised trials are needed before definitive conclusions can be drawn about the role of adding radiotherapy to chemotherapy in the treatment of PCNSL.
Several epidemiological studies of critically ill patients highlight a direct association between low levels of calcium (hypocalcemia) and mortality, though whether this association is causal is unknown. On the other hand, despite prior studies detailing associations between hypocalcemia and poor outcome, there is evidence to suggest that calcium supplementation in critical illness may be deleterious. Five randomized controlled trials with 159 participants were detected. All of the five included studies were conducted in the USA. No trial evaluated the association between parenteral calcium supplementation in critically ill intensive care unit patients and the following outcomes: mortality, multiple organ dysfunction, intensive care unit and hospital length of stay, costs, and complications of calcium administration. Some data on laboratory measurements (serum calcium) could be extracted. Nonetheless, these data provide little to guide the care of intensive care unit patients. The question of greater importance, "Does correcting hypocalcemia in critically ill patients provide any benefit in reducing mortality, the development of organ dysfunction, or the allocation of resources ?" remains to be answered. At present, the evidence base for guidelines regarding calcium administration in intensive care unit patients is poor.
We did not identify any trials comparing ambroxol with dexamethasone (corticosteroid) in this review. Nor did we identify any trials comparing ambroxol combined with corticosteroid versus corticosteroid alone, or placebo/no treatment. The review identified 14 small studies involving a total of 1047 women (and their 1077 newborns), that compared ambroxol with corticosteroid (betamethasone), or to placebo/no treatment. Three of the studies did not report on the outcomes of interest for this review. The results of the review are based on very low to moderate quality evidence. There were no clear evidence of differences in the incidence of RDS or perinatal mortality in newborns of women who were given ambroxol when compared with newborns of women who received either a corticosteroid (betamethasone) or placebo/no treatment. Similarly, there was no clear difference between groups in terms of nausea and vomiting (the only maternal adverse effects that were reported). For the review's secondary outcomes, none of the included studies reported on the incidence of bronchopulmonary dysplasia, periventricular haemorrhage, necrotising enterocolitis or rate of maternal mortality. One small study (comparing ambroxol with placebo/no treatment) found no difference between groups for the neonatal outcomes of 'need for mechanical ventilation' or 'administration of pulmonary surfactant'. There is insufficient evidence to support or refute the practice of giving ambroxol to pregnant women at risk of preterm birth for preventing neonatal RDS. More research in this area is necessary in order to evaluate the effectiveness and safety of this intervention.
The evidence is current to September 2014. We included 11 studies involving 6502 participants having 7018 surgical procedures (some participants had surgery on both breasts). Out of these, 2529 participants underwent nipple-sparing mastectomy, while there were no participants who had an areola-sparing mastectomy, 818 participants underwent skin-sparing mastectomy and 3671 underwent a traditional mastectomy. All participants in the studies were women and most of them (99.2%) had invasive breast cancer or ductal carcinoma in situ. We compared nipple-sparing mastectomy to conventional mastectomy and skin-sparing mastectomy in two different analyses. It was not possible to conclude whether or not survival following nipple-sparing mastectomy was similar to traditional mastectomy and skin-sparing mastectomy. Results were also inconclusive for differences in local recurrence and adverse events following different types of mastectomy. In practice the decision to select nipple-sparing mastectomy over other types of mastectomy should be done through shared decision making after extensive discussion of the risks and benefits. Generally the nipple-sparing mastectomy studies reported a favourable aesthetic result and a gain in quality of life compared with the other types of mastectomy. However, due to the lack of numerical data, it was not possible to pool the results of different studies. The quality of the evidence included in this review was very low. The studies had a number of methodological flaws. Poor reporting meant that the effect of the type of mastectomy on survival could not be determined for a number of studies. Also, differences between surgery groups in tumour stage and whether or not adjuvant radiotherapy was used may have affected the results. This is likely to have an impact on the findings and future research is likely to change the current findings.
We searched the literature up to November 2013 and found five studies (involving 13 dental auxiliaries, six dentists, and more than 1156 participants) evaluating the effectiveness of dental auxiliaries compared with dentists in providing care traditionally delivered by dentists for inclusion in this review. These studies evaluated only two clinical tasks/techniques: placement of preventive resin sealants, which are designed to prevent dental decay in the pits and grooves of back teeth; and the atraumatic restorative technique (ART), which is a method of filling teeth that does not require motorised instruments (e.g. dental drills). Two studies were conducted in the US, and one in each of Canada, Gambia and Singapore. Of the four studies comparing dental auxiliaries and dentists in placing preventive sealants, three found no differences between the two groups in the proportion of sealants that were still intact over different time periods (six to 24 months). One study found that fewer sealants placed by a dental auxiliary were still intact after 48 months than those placed by a dentist. The same study reported that dental decay was more likely to develop in teeth that had been sealed by the dental auxiliary than the dentist, whereas another study reported no evidence of a difference between the groups. The one study comparing the effectiveness of dental auxiliaries and dentists in performing ART reported no evidence of a difference in the proportion that needed replacing or that had developed new decay after 12 months. None of the studies reported adverse events. In addition, none of the studies compared the costs and cost effectiveness of dental auxiliaries and dentists, or considered any impacts on access to care. Too few studies were included in this review to draw any firm conclusions about the relative effectiveness of dental auxiliaries and dentists. The included studies, of which four were more than 20 years old, were of low quality, had few participants and only considered two clinical tasks. This review highlights the lack of high-quality studies comparing the effectiveness, and cost-effectiveness, of dental auxiliaries and dentists in performing dental care traditionally delivered by dentists.
Data from 5 randomized trials, which included a total of 3101 patients and evaluated the effect of bevacizumab, are currently available. Furthermore, data from one study, which included a total of 1168 patients and evaluated the effect of valatinib is published. The addition of bevacizumab to chemotherapy prolongs both progression-free survival from about 7.1 to 9.7 months when used as primary treatment and overall survival from about 17.7 to 20.5 months after prior use of chemotherapy (so called "second-line therapy") for metastatic colorectal cancer. However, the magnitude of the effect on progression-free survival is variable and probably depends on the type of chemotherapy to which it is associated. Vatalanib has no significant effect on progression-free and overall survival. Adverse effects of bevacizumab include increased frequencies of high blood pressure, arterial thromboembolic events and bowel perforations.
The reviewers found no strong evidence for the effectiveness (or ineffectiveness) of psychosocial interventions by general practitioners. Of the psychosocial interventions reviewed, problem-solving treatment for depression seems the most promising tool for GPs, although its effectiveness in daily practice remains to be demonstrated.
We found 11 trials involving 1836 caregiver participants in total. The trials commonly evaluated an intervention that provided emotional support and advice on coping. Two studies aimed to help support the family and friends indirectly by addressing the needs of the patient. Apart from one trial providing patient care, none provided practical support. Trials compared those who received the intervention with those who did not, to see if the intervention helped the family, family member or friend cope with their caring role. Trials commonly evaluated the intervention by measuring whether it improved the caregiver's general wellbeing. The review found that interventions that directly support the family and/or friends help them to cope emotionally, and may help them to cope with their role in caring and improve their quality of life. There were few assessments of the impact of the interventions on physical health; one study found overall no difference in sleep improvement. No study looked at whether the interventions increased or decreased the carers' health service use or looked for potential harms, although higher levels of family conflict was identified in some participants in one trial. Interventions that aimed to help support the family and/or friends indirectly via patient care, may also help them cope emotionally. There were no assessments on whether the indirect interventions helped them cope with their role in caring, improved quality of life, increased or decreased their health service use, or had potential harms. In one of these trials there was no difference in caregiver physical health between those whose friend or relative had received the additional patient care, and those who had not. The findings of some studies included in this review may be at risk of bias, because they under-report key design features and may have been conducted poorly.
Evidence is current to September 2016. We identified six randomised studies, with a total of 822 participants, that explored the management of intussusception in children and assessed different types of interventions. We also identified three ongoing trials. The main outcome was the number of children with a successfully reduced intussusception. Furthermore, outcomes included the number of children returning with a recurrent intussusception and evaluation of harms (adverse events) resulting from the interventions. Evidence from two studies suggests that using air for the enema to reduce intussusception is superior to using liquid for the enema. Evidence from two studies also suggests that giving the child with intussusception a steroid medication, such as dexamethasone, may reduce the recurrence of intussusception, irrespective of whether liquid or air is used for the enema.  We identified only sparse information on intraoperative and postoperative complications and on other adverse events. Of the six trials identified, we considered all to be potentially biased owing to lack of detail in reporting of how each study was undertaken. We found lack of consistency in how outcomes were defined and measured. All included studies were subject to serious concerns of imprecision based on few events, wide confidence intervals,or high risk of bias, Overall, we concluded that the quality of evidence provided by these studies was low, and that the real effects may differ significantly from those noted in these studies.  Further research is needed to help doctors better understand the most effective way to manage intussusception in children.
Authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 14 August 2014. It includes 10 studies published from 1991 to 2014 in which 7969 participants were randomised (5903 of whom were included in the analyses) to receive xylitol products or a placebo (a substitute without xylitol) or no treatment, and the amount of tooth decay was compared. One study included adults, the others included children aged from 1 month to 13 years. The products tested were the kind that are held in the mouth and sucked (lozenges, sucking tablets and sweets) or slowly released through a dummy/pacifier, as well as toothpastes, syrups, and wipes. There is some evidence to suggest that using a fluoride toothpaste containing xylitol may reduce tooth decay in the permanent teeth of children by 13% over a 3 year period when compared to a fluoride-only toothpaste. Over this period, there were no side effects reported by the children. The remaining evidence we found did not allow us to conclude whether or not any other xylitol-containing products can prevent tooth decay in infants, older children, or adults. The evidence presented is of low to very low quality due to the small amount of available studies, uncertain results, and issues with the way in which they were conducted.
Recent studies have suggested that an injection of anti-vascular endothelial growth factor (anti-VEGF) in the eye may be of benefit to patients with BRVO. In this review, we appraise and present the level of current evidence for the use of anti-VEGF injections in the treatment of macular oedema after BRVO. In total, we found one randomised controlled trial and one quasi-randomised controlled trial. One study from the USA. had 397 participants and compared anti-VEGF injections with sham injections. It demonstrated a potential benefit of repeated anti-VEGF injections to improve vision (at least 15 letters) at one year. A second study with 30 participants, conducted in Italy, compared anti-VEGF injections with laser photocoagulation and did not demonstrate an improvement in vision (of at least 15 letters) of anti-VEGF injections over laser photocoagulation at one year. Antiangiogenic treatment was well tolerated in these studies, but since the studies were only of one year duration, we were unable to discuss long-term effects. There are several ongoing studies which undoubtedly will add to the evidence available.
The quality of included studies was generally very low due to the risk of bias, small sample size, and a lack of information. We found very low quality evidence that fixed reduction of dialysate temperature decreased the incidence of IDH compared with standard dialysate and increased the discomfort rate. When patient discomfort is minimal, reduction of the dialysate temperature may be an option to reduce IDH. However, no study reported the long-term outcomes such as death or heart disorders. There is limited data suggesting that the reduction of dialysate temperature may prevent IDH, but the conclusion is very uncertain. Larger studies that measure important outcomes such as IDH or mortality for HD patients are required to assess the effect of reducing dialysate temperature.
The evidence was current to April 2013. We found 12 studies involving 774 patients. The age of the participants, in the studies, ranged from 19 to 80 years. Types of surgery and anaesthesia varied. The melatonin doses varied from 3 to14 mg and were administered 50 to 100 minutes before surgery. Midazolam (a benzodiazepine) doses ranged from 3.5 to 15 mg. We reran the search in October 2014. We will deal with any studies of interest when we update the review. Four studies compared melatonin, placebo and midazolam; eight studies compared melatonin and placebo only. Comparing the effect of melatonin with placebo, melatonin may reduce preoperative anxiety. It may also reduce postoperative anxiety compared with placebo, measured six hours after surgery. When comparing the effect of melatonin with midazolam preoperatively, there was no difference in anxiety. Postoperatively, there was no difference when comparing the effect of melatonin with placebo on anxiety measured 90 minutes after surgery or when comparing the effect of melatonin with midazolam. The quality of the evidence varied by outcome. We are confident that melatonin reduces anxiety preoperatively from the short term data in the review. We are less certain of this effect six hours postoperatively. Whether the anxiety reducing effect of melatonin can be applied to all surgical patients remains unclear, as many factors influence the risk of anxiety; among these are age, gender, type of surgery, type of anaesthesia, and cultural and religious differences. Younger age and female gender are independent risk factors for anxiety and this may be a limitation as four studies only included women and three only included patients older than 60 years. Eight studies were carried out in Middle-East countries; this might be a limitation with regard to generalizability. Melatonin compared to placebo, given as premedication (tablets or under the tongue (sublingually)) reduced preoperative anxiety (measured 50 to 100 minutes after administration). Melatonin may be equally as effective as standard treatment with midazolam in reducing preoperative anxiety (measured 50 to 100 minutes after administration). When compared to placebo, melatonin may reduce postoperative anxiety (six hours after surgery).
We included 14 randomised clinical trials with 867 participants. All randomised clinical trials compared intravenous infusion of flumazenil versus an inactive placebo (dummy infusion, e.g. a salt solution). The duration of treatment ranged from 10 minutes to 72 hours. Ten randomised clinical trials included participants with overt hepatic encephalopathy; three included participants with minimal hepatic encephalopathy; and one randomised clinical trial included participants with overt or minimal hepatic encephalopathy. The analyses showed no effect of flumazenil on all-cause mortality (deaths of any cause) compared with placebo. People who received flumazenil were more likely to recover from their hepatic encephalopathy than people given a placebo. We found little information about serious side effects. Overall, the evidence for the effect of flumazenil on hepatic encephalopathy was of low quality; only one randomised clinical trial included had a low risk of bias.
The aim of the review was to examine the effectiveness and safety of perphenazine for schizophrenia. A search for relevant randomised studies was run in September 2013. The review authors included 31 studies that randomised people with schizophrenia to receive either perphenazine or placebo or another antipsychotic drug. A total of 4662 people participated in these studies. The quality of evidence presented by the trials was rated by the review authors to be very low quality. It was found that perphenazine was no better or worse than other older antipsychotic drugs in treating the symptoms of schizophrenia, and like other older antipsychotic drugs, the side effects of perphenazine included tremors, uncontrollable shaking, the inability to sit still and feeling restless. Although perphenazine has been used for more than 50 years, poor studies with bad reporting of information mean that it is difficult to draw more clear findings and conclusions as to the effectiveness and safety of perphenazine. However, perphenazine is inexpensive and a popular antipsychotic drug in many countries, so further research and trials on its effectiveness and safety are much needed. Ben Gray, Senior Peer Researcher, McPin Foundation.http://mcpin.org/
All of the reviews were considered to be well-conducted. However, the individual trials included in the reviews often did not report enough detailed information to allow us to properly determine trial quality. Many trials did not report enough information on outcome measures; it is unclear how this missing information would influence the results. We graded the evidence for lung function when PEP was compared to vibrating (oscillating) devices as moderate, but the evidence comparing different airway clearance techniques for other outcomes, such as individual preference and quality of life was of low or very low quality. More long-term, high-quality trials (where participants are put into groups at random) which compare different airway clearance techniques among people with CF are needed.
Many of the early trials used unsatisfactory methods, were small, and publication bias cannot be excluded. Overall, evidence that Ginkgo has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unreliable. Of the four most recent trials to report results, three found no difference between Ginkgo biloba and placebo, and one reported very large treatment effects in favour of Ginkgo biloba.
We searched scientific databases from their inception to 1 April 2016 and found three studies where people are randomly allocated into one of two or more treatment groups (known as randomised trials). The three trials included 261 adults (mean age: 60 years) comparing catheter ablation (159 participants) to heart rhythm drugs (102) for non-paroxysmal atrial fibrillation at 12 months follow-up. When compared to participants receiving heart rhythm drugs, those participants receiving catheter ablation were more likely to be free from atrial fibrillation, had reduced risk of being hospitalised due to cardiac causes, and had a reduced risk of needing cardioversion after 12 months. There was uncertainty surrounding the effect of catheter ablation with significant bradycardia (or need for a pacemaker), periprocedural complications, and other safety outcomes. Evidence should be interpreted with caution as evidence quality ranged from moderate to very low across the different outcomes due to the limitations of the original studies. It is likely that further high-quality and adequately powered trials may affect the confidence in reported results.
This review identified three randomized controlled trials involving 104 patients. Two studies compared progressive resistance training with standard care (usual treatment process). When we combined their results we found that progressive resistance training improved shoulder pain, shoulder disability, active range of motion for external rotation, passive range of motion for abduction, forward flexion, external rotation and horizontal abduction. The size of this improvement was small. The studies did not demonstrate a statistically significant difference in quality of life. Two non-serious adverse events were reported in the progressive resistance training group and none in the standard care group. Another study compared a broad spectrum of techniques, including free active exercises, stretching, postural care, re-education of scapulothoracic postural muscles, and strength of shoulder muscles, with routine postoperative physiotherapy care for three months following surgery. This study did not demonstrate a difference between the exercise group and the routine physiotherapy care group in shoulder function or quality of life. No adverse effects were reported. Further studies which apply other exercise interventions in head and neck cancer patients in the early postoperative period and after radiotherapy are needed, with long-term follow-up.
Moderate quality evidence was available from the two included studies which compared the Bishop score with transvaginal ultrasound (TVUS) (ultrasound done through the vagina). The studies were considered to be at a low risk of bias. The need for misoprostol (a drug) for softening the cervix (cervical ripening) was more common in the TVUS arm. No clear difference was seen between the two methods in terms of vaginal birth, caesarean delivery, admission of the newborn into the neonatal intensive care unit, meconium staining of the amniotic fluid, abnormal heart beat of the baby within the womb whilst the mother was in labour and Apgar score less than seven (difficulty of the baby establishing life and other life movements on its own immediately after childbirth). None of the included studies reported on tears of the womb or death of the baby just before, during or immediately after childbirth. We did not find any studies that compared Bishop score with any other methods such as the presence of vaginal fetal fibronectin or insulin-like growth factor binding protein-1. Authors conclusions Although the overall quality of evidence is moderate, there is no difference in outcomes between the two methods (Bishop score and TVUS) apart from the increased need of misoprostol in the TVUS group. Both methods could be useful to each other, or complementary as the Bishop score does not need any special equipment and uses digital examination which is required to induce labour (to insert a cervical ripening agent, rupture the membranes or separate them from the cervix) but TVUS can give additional information that may affect the course and management of the labour. The choice of a particular method may differ depending on the environment and need since TVUS requires training and may not be readily available and affordable in resource-poor countries. Future research  The two included studies involved a small number of women and further studies are needed. Such studies should include outcomes such as rupture of the womb, perinatal mortality, most appropriate cut-off value for the cervical length and Bishop score to classify women as having ripe or unripe cervices, and cost.
Data from two small studies were available for inclusion in this review; however, both studies were in infants following hospitalisation for an acute bronchiolitis illness (98 infants in total). There was no difference between groups in the proportion of children 'not cured' at follow-up. There were no significant side effects in either of these studies. Without further available evidence, recommendations for the use of inhaled corticosteroids for the treatment of subacute cough in children cannot be made. Further well-designed studies, including children over 12 months of age, are required to determine whether treatment with inhaled corticosteroids can safely and effectively reduce the severity of subacute cough in children.
Our searches of the medical literature revealed one relevant study, which was in infant botulism. The treatment was a single dose of a medicine made from human immune proteins (human-derived botulinum immune globulin intravenous, or BIG-IV). Fifty-nine infants received BIG-IV, and 63 infants received a placebo (inactive treatment). Each study participant was followed up for the duration of their hospitalization. This study was sponsored by the California Department of Health Services. There were no deaths in either group in the trial. Infants treated with BIG-IV spent, on average, about three weeks less time in hospital (i.e. 3.1 weeks versus 5.7 weeks) than infants who received the inactive treatment, and spent about three weeks less on a ventilator (1.8 weeks versus 4.4 weeks). The average duration of tube feeding in the BIG-IV group was more than six weeks less than in the placebo group (i.e. 3.6 versus 10 weeks). The risk of harmful effects of the treatment was probably no greater with BIG-IV than with the inactive treatment. The evidence was mostly of moderate certainty (low certainty for time spent on a ventilator). The review shows that BIG-IV probably shortens hospitalization; may shorten time spent on a ventilator; and probably reduces the duration of tube feeding compared to placebo. On the other hand, we found no evidence for or against botulism antitoxin or other treatments for botulism. The evidence is up-to-date to January 2018, when we updated the searches and found no new trials.
In March 2017, we found 24 studies involving 5220 people. The main comparison was between usual oral doses of ketoprofen 50 mg and placebo, and dexketoprofen 25 mg and placebo. The studies tested single doses after wisdom tooth extraction, and after other types of surgery, mainly hip replacement and gynaecological operations. Studies included adults over a range of ages, and 7 out of 10 participants were women. The main outcome was participants having at least half of the maximum possible pain relief over the first six hours after taking the tablets. For ketoprofen, there were 594 participants in eight studies in the comparison with placebo (a dummy tablet). About 6 in 10 achieved at least half of the maximum possible pain relief with ketoprofen 50 mg compared with 2 in 10 with placebo. The number of participants who needed more painkillers within six hours was 5 in 10 with ketoprofen compared with 8 in 10 with placebo. For dexketoprofen, there were 1177 participants in eight studies in the comparison with placebo. About 5 in 10 achieved at least half of the maximum possible pain relief with dexketoprofen 25 mg compared with 3 in 10 with placebo. The number of participants who needed more painkillers within six hours was 5 in 10 with dexketoprofen compared with 7 in 10 with placebo. About 1 or 2 in 10 people had any side effects with ketoprofen, dexketoprofen, or placebo. Serious side effects were uncommon. Few people dropped out of the studies for any reason. The quality of the evidence was judged to be high for most outcomes. This research provides a very good indication of the likely effect. The likelihood that the effect will be substantially different is low.
This updated review found in the world literature 33 randomised controlled trials (RCTs) of culturally appropriate health education on diabetes that met the selection criteria (participants from a defined ethnic minority group living in a upper-middle-income or high-income country, over 16 years of age, diagnosed with type 2 diabetes mellitus and receiving a culturally tailored health education intervention). The median duration of the intervention was six months, and a total of 7453 participants were involved in the studies. Culturally appropriate health education improved blood sugar control among participants, compared with those receiving 'usual' care, at three, six, 12 and 24 months after the intervention was provided. Knowledge about diabetes improved, and participants attained healthier lifestyles. No information was available regarding complications of diabetes and death from any cause, and there was a general lack of reporting of adverse effects in most studies. Neutral effects were observed for health-related quality of life, blood lipids like cholesterol, blood pressure and weight. The costs of educational programmes were rarely analysed. Compared with the first review, performed in 2008 (11 studies), many more published studies were identified in this review (altogether 33 studies), strengthening the original findings that blood sugar control and knowledge of diabetes are improved when culturally appropriate health education is provided to people in ethnic minority groups diagnosed with diabetes. The effects of this improvement are shown in this update as lasting longer — up to 24 months after health education was provided in some trials. However, additional high-quality standardised RCTs of longer duration are needed, along with full evaluation of costs. Heterogeneity of the studies, in terms of populations studied, type and duration of health education provided, variety of outcomes measured and differences in timing of assessment, limits interpretation of our findings. Also, risk of bias was judged to be high for many outcomes. This evidence is up-to-date as of September 2013.
This review aimed to identify clinical trials to assess the effect of different types of bereavement support interventions and/or counselling for parents experiencing perinatal death. There are no included studies on this topic. For the update of this review we identified one new trial, which is currently awaiting classification. More research in this area is needed.
We searched for evidence in September 2017 and included eight trials involving 4009 women receiving ergometrine by mouth (orally), into the muscle (intramuscularly (IM)) or into the vein (intravenously (IV)). Of eight trials, seven included studies were analysed in this updated review. The evidence from the trials analysed suggests that ergot alkaloids may decrease mean blood loss, increase maternal haemoglobin levels in the blood, and may decrease both blood loss of at least 500 mL (PPH) and the use of therapeutic uterotonics. It is uncertain whether ergot alkaloids have any effect on numbers of women experiencing high blood loss of at least 1000 mL (severe PPH). The evidence also suggested that they may increase adverse effects such as increased blood pressure and pain after birth. They may make little or no difference between groups in terms of other adverse effects (vomiting, nausea, headache or eclamptic fit) and results were inconsistent on the risk of retained or manual removal of placenta. Most of the evidence came from trials that administered ergot alkaloids using the IM or IV route. There was only one small trial that looked at the use of oral ergot alkaloids and results were inconclusive. There were limited numbers of included studies and results between studies were not always consistent or precise. Overall quality of evidence across critical and important outcomes ranged from very low to moderate. The IV or IM route, although it may reduce blood loss and PPH, was associated with the adverse effects of raised blood pressure and pain due to contractions of the uterus. There was not enough evidence on the oral route of administering ergot alkaloids. There are other medications, namely oxytocin, syntometrine and prostaglandins (which are assessed in other Cochrane Reviews), that can be used and may be preferable.
We found 24 trials that randomly assigned participants to take either an ARB or control substance (placebo or ACEI). These trials evaluated ARBs in 25,051 patients with heart failure and followed them for 2 years. ARBs were no better than placebo or ACE inhibitors in reducing the risk of death, disability, or hospital admission for any reason. However, more patients stopped treatment early with ARBs than with placebo due to side effects. Adding an ARB to an ACEI also did not reduce the risk of death, disability, or hospital admission for any reason as compared to ACEI alone, although more patients taking the combination stopped early due to side effects.
Randomised studies have been successfully conducted in this area but poor study reporting meant that no conclusions could be drawn from them. The benefits or harms of the use of drama therapy in schizophrenia are therefore unclear and further large, high quality studies are required to determine the true value of drama therapy for schizophrenia or schizophrenia-like illnesses.
Two good quality randomized controlled trials involving 754 women were identified. Rapid negative pressure application reduced the duration of the procedure without any evidence of differences in outcomes for the mother or infant. Rapid method of negative pressure application should be recommended for vacuum extraction assisted vaginal delivery.
We searched up to 1 February 2015 and found four studies with a maximum of 334 participants with information for analysis. Ibuprofen 200 mg plus caffeine 100 mg provided effective pain relief for 6 in 10 (59%) participants, compared with 1 in 10 (11%) participants with placebo (moderate quality evidence). Adverse events occurred at similar rates with the ibuprofen plus caffeine combination and placebo in these single dose studies (low quality evidence). No serious adverse events or withdrawals due to adverse events occurred with the combination. The combination of ibuprofen 200 mg + caffeine 100 mg is not commonly available, but can probably be achieved by taking a single 200 mg ibuprofen tablet with a cup of modestly strong coffee. Common sources of caffeine include not only caffeine tablets (100 mg is sufficient), but coffee (100 mg to 150 mg per mug or cup with a volume of about 240 mL or 8 fl oz, or a double espresso), but also tea (75 mg per mug), cola drinks (up to 40 mg per drink), energy drinks (approximately 80 mg per drink), plain chocolate (up to 50 mg per bar), and caffeine tablets (100 mg per tablet). Some people may get good levels of pain relief with a lower dose of ibuprofen when the ibuprofen is combined with caffeine.
Our search found one trial with 46 adult volunteers with cystic fibrosis which compared nasal drops containing a steroid (betamethasone) to identical drops containing no active treatment. Two drops were applied directly to polyps twice a day for six weeks. Volunteers were put into the different treatment groups at random and a total of 22 volunteers received the steroid drops and 24 received the dummy treatment. The trial measured each person's perception of their symptom scores, but found no difference to the scores whether volunteers were using the steroid drops or the dummy treatment. The trial also measured the change in polyp size and found that they shrank. There were no major side effects linked to using betamethasone, and only three volunteers reported increased nose bleeds and discomfort. The small number of volunteers in this trial means the calculations and results should be regarded with some caution. More trials are needed to confirm the findings and these trials should report on measures of symptoms and quality of life issues. We think that volunteers had a truly equal chance of being put in either the steroid group or the control group and wouldn't have known which treatment they were receiving, so these issues would not have influenced the results in any way. However, over 50% of people enrolled did not complete the study and the reasons for dropping out were not very clearly explained. We think it is important to take this fact into account when considering the trial results. Also, the trial only followed the volunteers for six weeks, which is a short time when evaluating a treatment that could be needed for the rest of a person's life.
This review includes 15 studies with a total of 487 people with CF; the numbers in each study ranged from just nine people up to 72 people in the largest study. Two studies were in adults, seven were in children and adolescents and six studies included all age ranges. Four studies lasted less than one month and took place while the participants were in hospital; 11 studies were outpatient-based and lasted from two months up to three years. The studies included people with a wide range of severity of CF lung disease. There were differing levels of supervision in the studies and a mixture of types of training. The outcome most often reported in the studies was the change in lung function; other commonly reported outcomes included peak oxygen consumption, health-related quality of life, change in muscle strength and change in body composition (e.g. muscle and fat). Due to different study designs (type of exercise training, duration, etc.), we could not combine results from different studies. The short-term studies did not show differences between treatments. The longer studies showed that physical exercise training can improve aerobic capacity, there were some improvements in lung function and health-related quality of life, but these were not consistent across all studies. No study reported the number of deaths; two studies reported on side effects; one study reported on pulmonary exacerbations and another on diabetic control. We included a number of small studies and thought the quality of these studies was moderate at best (only for side effects). Overall, there was only low- to very low-quality evidence that aerobic or anaerobic physical exercise training (or a combination of both) has a positive effect on aerobic exercise capacity, pulmonary function and health-related quality of life in people with CF. In four of the studies the participant characteristics at the start of the studies were different between groups, despite being put into the different treatment groups at random. It is not possible for people not to know which treatment group they are in when comparing exercise training to no exercise. However, we do not think the fact that people knew which treatment they were receiving would affect the results for lung function as long as the assessments were done properly. In contrast, there may be bias when the people assessing an individual's cardiopulmonary fitness are not blinded to which group the volunteer is in. In less than half of the included studies, the investigators tried to prevent the outcome assessors from knowing which groups the participants were in; and in only one study was the lead researcher blinded. The studies did not routinely measure health-related quality of life and where it was measured, different measurement tools were used. Selective reporting of results maybe an issue, especially as most of the included studies were not listed in trial registries, which give advance details of the outcomes being measured. We are uncertain about the effects and further better quality studies will likely change these findings.
This review therefore assessed the effectiveness of CoQ10 supplementation for CVD prevention. We included trials administering CoQ10 as a single supplement in healthy adults or those at high risk of CVD (but without a diagnosis of CVD) and measuring cardiovascular events or major CVD risk factors, such as blood pressure and lipid levels. We found six completed randomised controlled trials with a total of 218 participants randomised. All were conducted in participants at high risk of CVD. Two examined CoQ10 supplementation alone and four examined CoQ10 supplementation in patients on statin therapy. The trials were small and short-term, none measured cardiovascular events or adverse events, and we regarded two of the six trials as being at high risk of bias. Very few small trials contributed to the analyses and no conclusions can be drawn at this time. We also identified five ongoing trials and the results from these will add to the evidence base in due course. More longer-term trials are needed to determine the effect of CoQ10 on cardiovascular events.
We reviewed a total of eight studies involving 262 participants between the ages of five and 18 years with well-controlled asthma. They underwent swimming training varying from 30 to 90 minutes two to three times a week over six to 12 weeks in seven studies, and in one study training lasted 30 minutes six times per week. This review found that for swimming training compared to control (either usual care or another physical activity), there were improvements in resting lung function tests, but no effects were found on quality of life, control of asthma symptoms or asthma exacerbations. Physical fitness increased with swimming training compared with usual care. There were few reported adverse asthmatic events in swimming training participants during the programmes. The relatively small number of studies and participants limits this review’s ability to measure some outcomes that are of interest, particularly the impact on quality of life and  asthma exacerbations. In summary, swimming training is well-tolerated in children and adolescents with stable asthma, and increases physical fitness and lung function. However, whether swimming is better and/or safer than other forms of physical activity cannot be determined from this review. Further studies with longer follow-up periods may help us understand any long-term benefits of swimming.
We identified one randomised controlled trial, which involved people with a penetrating injury to the chest. In this study, 44 people (mostly male and with similar characteristics in terms of type of injury) were given either their own reprocessed blood (through cell salvage) or standard care using donated blood. The study was conducted at a hospital in Johannesburg, South Africa in 2002. Results indicated no important differences between the two groups of participants with regard to survival, postoperative infection, or cost. There was a reduction in the amount of banked blood (blood that has been donated and stored) required for transfusion within the first 24 hours following injury among people receiving cell salvage. Data on other adverse events were not reported. We believe that larger, multicentre, methodologically rigorous trials are needed to assess the relative efficacy, safety and cost-effectiveness of cell salvage in trauma surgery and other surgical procedures. The quality of the one study identified was high, but the number of participants was not large. No firm conclusions can be drawn as to the safety and effectiveness of cell salvage in individuals undergoing abdominal or thoracic trauma surgery.
A total of twenty-five randomised studies (including 3752 patients) were included in this updated review: nineteen trials (2728 patients) comparing concurrent chemoradiotherapy with radiotherapy alone and six trials (1024 patients) comparing concurrent with sequential chemoradiotherapy. Both comparisons demonstrated significant reduction in risk of death with use of concurrent chemoradiation, with an associated increase in incidence of acute oesophagitis.
We found 21 randomised controlled trials that compared UGET with clinical touch in a total of 6218 women. The evidence is current to May 2015. Live birth/ongoing pregnancies were increased for the ultrasound-guided group compared with the clinical touch group, based on low-quality evidence. We estimate that for women with a chance of a live birth/ongoing pregnancy of 23% using clinical touch, this would increase to between 28% and 33% using UGET. Data for live birth should be interpreted carefully, as differences between the studies make drawing a conclusion difficult. The evidence suggests that in studies that used the same brand of transfer catheter in both the ultrasound-guided and the clinical touch groups, ultrasound guidance was linked to an increase in the chance of a live birth. There was no evidence that the risk of harm using UGET, including miscarriage, ectopic pregnancies, and multiple pregnancies, is any different than when clinical touch is used to guide the embryo transfer. The quality of the evidence for live birth/ongoing pregnancy was low due to poor reporting of study methods and inconsistency in trial results.
The review aims to determine what length of stay in hospital is the most helpful and is now based on a 2012 search. Six randomised trials are included that compare short stay in hospital with either long stay in hospital or standard care. No differences were found between groups in readmission to hospital, mental state, leaving the study early, risk of death and people lost to follow-up. There was a significant difference favouring short-stay hospitalisation for social functioning. There was limited information that suggested that short-stay hospitalisation does not encourage a ‘revolving door’ pattern of admission to hospital and disjointed or poor care. This should reassure people with mental illness coming into hospital that a short stay (of less than 28 days) means they are no more likely to be readmitted, to leave hospital abruptly, or to lose contact with services after leaving hospital than if they received long-stay care. Short-stay patients are also more likely to leave hospital on their planned discharge date and possibly have a greater chance of finding employment. For psychiatrists, policy makers and health professionals it is important to know that short-stay hospitalisation does not lead to a ‘revolving door’ pattern of admission to hospital and poor or fragmented care. However, all evidence in this review was rated by the review authors to be low quality. More large, well-designed and well-reported trials are justified that focus on important outcomes such as death, self-harm, harm to others, employment, criminal behaviour, mental state, satisfaction with treatment and services, homelessness, social or family relationships and costs. This plain language summary has been written by a consumer Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness.
The review authors examined the available evidence up to 17 June 2016, and included four trials with a total of 3198 children under five years of age. The included trials were conducted in Afghanistan, Spain and the USA. The review did not detect an effect of vitamin D supplementation on death (low quality evidence); the occurrence of the first or only episode of pneumonia; or on children with pneumonia, irrespective of whether this had been confirmed by hospital tests (moderate quality evidence). Limited evidence showed that there was no obvious difference in the first or repeat episodes of diarrhoea between supplemented and unsupplemented children. We do not know about whether Vitamin D influences hospital admissions as there was only one small study measuring this (very low quality evidence). The mean serum vitamin D concentrations were higher in the supplemented versus unsupplemented children at the end of supplementation period (low quality evidence). One large trial from Afghanistan showed an increase in repeat episodes of confirmed pneumonia but not on confirmed and unconfirmed pneumonia. None of the included trials reported on TB or malaria as outcomes. One large trial has not demonstrated an effect of vitamin D on death or respiratory infections in children under five years of age. We did not find trials evaluating Vitamin D supplementation to prevent other infections such as TB and malaria.
This review identified 21 studies with a total of 1371 children. Behavioural interventions when used together with laxative therapy may improve continence in children with non-organic faecal incontinence and constipation whilst biofeedback does not add any long-term benefit. Children who received biofeedback treatment had not always been evaluated beforehand for the suitability of the treatment. There was not enough evidence to assess the effects of biofeedback in children with organic faecal incontinence.
This is an update of a previous review. The first version was published in 2012 and included seven studies. For this update we searched for new studies in December 2016 and found one. This review now includes eight trials. Seven of these were trials of the 'Smokefree Class Competition' (SFC), which has been widely used throughout Europe. In this competition, classes (generally between the ages of 11 and 14 years) promise to be smoke-free for a six-month period. They report regularly on their smoking status, and if 90% or more of the class are non-smokers at the end of the six months, the class goes into a competition to win prizes. In the one trial that did not test the SFC, classes with the smallest percentage of students smoking at the school year's end were given rewards. We assessed the results from seven trials of SFC and found that the competition did not have a significant impact on whether or not young people started smoking. As there was only one trial that was not of the SFC, we concluded that we do not have enough information to evaluate whether this programme was effective in preventing young people from starting to smoke. Potential negative effects of the SFC have not been widely researched, but the available data suggest that the SFC programme does not have any significant negative effects. We judged the overall quality of evidence to be low or very low, because it is based on a small number of studies, with imprecise effects and with a high or uncertain risk of bias.
The aim of this review was to evaluate the effectiveness of various treatments for growth failure in childhood Crohn's disease. Three randomized controlled trials were identified. One trial did not show any benefit for linear growth with 6-mercaptopurine treatment compared to placebo among children being treated with steroids. The other two trials looked at nutritional treatment (elemental feedings) versus steroids (prednisolone). Both trials showed a statistically significant benefit for height velocity standard deviation scores with nutritional treatment. However, these results need to be confirmed by large, multi-centre, randomized controlled trials of therapeutic interventions in pre-pubertal children with Crohn's disease. These trials should use growth as an outcome measure. In conclusion, more research is needed to identify effective treatments for growth failure in childhood Crohn's disease.
This review looks at whether antibiotics, given to dental patients as part of their treatment, prevent infection after tooth extraction. There were 18 studies considered, with a total of 2456 participants who received either antibiotics (of different kinds and dosages) or placebo, immediately before and/or just after tooth extraction. There were concerns about aspects of the design and reporting of all the studies. In all of the studies healthy people had extractions of impacted wisdom teeth done by oral surgeons. This review provides evidence that antibiotics administered just before and/or just after surgery reduce the risk of infection, pain and dry socket after wisdom teeth are removed by oral surgeons, but that using antibiotics also causes more (generally brief and minor) side effects for these patients. Additionally, there was no evidence that antibiotics prevent fever, swelling or problems with restricted mouth opening in patients who have had wisdom teeth removed. There was no evidence to judge the effects of preventative antibiotics for extractions of severely decayed teeth, teeth in diseased gums, or extractions in patients who are sick or have low immunity to infection. Undertaking research in these groups of people may not be possible or ethical. However, it is likely that in situations where patients are at a higher risk of infection that preventative antibiotics may be beneficial, because infections in this group are likely to be more frequent and more difficult to treat. Another concern, which cannot be assessed by clinical trials, is that widespread use of antibiotics by people who do not have an infection is likely to contribute to the development of bacterial resistance. The conclusion of this review is that antibiotics given to healthy people to prevent infections, may cause more harm than benefit to both the individual patients and the population as a whole.
However, human trials have shown mixed results thus far. Therefore, we systematically reviewed all available clinical trial evidence as of July 2012 to determine if creatine benefits or harms people with ALS/MND. This review included three well-designed clinical trials involving a total of 386 participants receiving either creatine or placebo. Overall, creatine was well-tolerated with no serious side effects. Using various statistical methods, we found that creatine at a dose of 5 to 10 g per day did not improve ALS survival or slow ALS progression in any meaningful way. There was a hint that creatine may slightly worsen breathing ability, but this may have just been misleading statistical variability.
The review of trials attempted to cover all these. The authors identified 22 small trials involving 2676 people, with 19 of the trials taking place in resource-poor countries. Permethrin appeared to be the most effective topical treatment for scabies, and ivermectin appeared to be an effective oral treatment. However, ivermectin is unlicensed for this indication in many countries. Adverse events such as rash, vomiting, and abdominal pain were reported, but the trials were too small to properly assess serious but rare potential adverse effects. No trials of herbal or traditional medicines were identified for inclusion.
The ultrasound scan protocols in each trial varied, as did the reasons for ultrasound scans after 24 weeks' gestation. The influence of first and second trimester ultrasounds is difficult to disentangle, and assessment of most measures at late pregnancy is based on gestational reference data, which rely on accurate gestational dating in early pregnancy. Trials were undertaken over a period of time covering early introduction into clinical practice to widespread use, during which time how to assess fetal size and well being ultrasonographically were still being debated. As ultrasound technology continues to advance and become more accessible, it is important to maintain a clear idea of its relevance. Ultrasound, being a clinical investigation, may be used to detect abnormality without the impact of such detection on clinical outcomes being full assessed. Exposure of the expectant mother to uncertainty and possible anxiety about the health of her baby has implications that may be far reaching. In addition, little is known about how the baby that was compromised in the uterus develops after birth and in the first years of life.
We included 11 trials involving 808 participants in our review. The methodological quality of the included studies was variable and the quality of the evidence was low because the outcomes of interest were only reported by one or two studies. Sensitive methods such as venography or sonography were not always used to diagnose DVT and the CPM was applied differently across studies, varying in range of motion, duration of CPM per day and the number of days after the surgery. The incidence of DVT or VTE was not clearly different in the CPM group compared with the control group of participants. This review did not find enough evidence from randomised controlled trials to conclude that CPM reduces VTE.
This review also showed that in patients with typical or diarrhoea associated haemolytic uraemic syndrome, there are no interventions that are superior to supportive therapy which includes control of fluid and electrolyte imbalance, use of dialysis if required, control of hypertension and blood transfusion as required.
We searched the medical literature for randomised clinical trials (where people are allocated at random to one of two or more treatment groups) in order to perform an analysis of the role of radiotherapy administered externally for advanced liver cancer. We found nine randomised clinical trials including a total of 879 people with advanced liver cancer. All of the included trials were conducted in China. The average age in most of the included studies was around 52 years, and most trial participants were male. The average follow-up duration ranged from one to three years. All trials were at high risk of bias, and we rated the evidence as low to very low quality. Most of the included trials compared combined radiotherapy and chemoembolisation versus chemoembolisation alone. We also identified seven ongoing randomised clinical trials. The evidence is current to October 2016. When compared with chemoembolisation alone, combined radiotherapy plus chemoembolisation may be associated with fewer deaths and more tumour size reduction, despite being associated with an increased risk for non-life-threatening adverse effects such as a higher rise of bilirubin and alanine aminotransferase. Combined radiotherapy and chemoembolisation may be associated with fewer deaths and increased overall response, but also an increased risk of adverse effects, when compared with chemoembolisation alone. The low quality of evidence suggests that these results should be considered cautiously and that high-quality randomised trials should be performed to assess further the role of external beam radiotherapy for unresectable hepatocellular carcinoma.
We decided to review clinical trials that had participants who took antioxidants for at least 12 months, as Friedreich ataxia is a slowly progressing condition. A wide search of the medical literature found four randomised controlled trials, but only two of them had published results in medical journals. One trial, involving 28 participants, compared idebenone to a placebo. The other, involving 44 participants, compared high-dose and very low-dose combined coenzyme Q10 and vitamin E. The two unpublished trials studied pioglitazone in 40 participants and idebenone in 232 participants, but we had no data. According to low quality evidence from two small published trials included in the review, antioxidants did not improve neurological symptoms in Friedreich ataxia. An additional large, unpublished study of idebenone reportedly found no benefit from idebenone for heart or neurological symptoms, but data are not available for checking and analysis. When published this trial will very likely influence our quality assessments and conclusions. Although some measures of heart wall thickness and mass decreased in the smaller of the two published trials, the quality of this evidence was low or very low and the importance of these findings is not clear. . Numbers of serious or non-serious adverse events were low and similar with antioxidants and placebo. The only serious adverse event that required withdrawal of an antioxidant was increased bowel frequency in one person receiving coenzyme Q with vitamin E. The evidence in the review is up to date to February 2016.
In October 2019, we searched for studies assessing the effects of ACP in people with heart failure. We included studies that delivered ACP, which included different methods such as discussion and consideration of individuals' values and preferences on future care and medical treatment compared to usual care strategies. This review included nine studies involving 1242 participants and 426 families/carers. Data from seven studies (876 participants) showed that ACP may increase completion of documentation by medical staff regarding discussions with participants about ACP processes and may improve depression of participants. All-cause mortality might be increased in participants receiving ACP. The effects of ACP on quality of life remained uncertain due to the inclusion of small studies in our meta-analysis. This is further illustrated by the fact that only one study reported whether the received end-of-life care met participants' preferences. Similarly, only one study reported the quality of communication during ACP between participants and healthcare providers. Therefore, the effects of ACP on whether end-of-life care met participants' preferences and on quality of communication were uncertain. None of the studies evaluated satisfaction with care. The quality of evidence was low/very low. Since the number of studies and patients in this review was small, the effects of ACP were limited. There is clearly a need for high-quality evidence from large studies to fully explore the effects of ACP for people with heart failure, in particular their quality of life and whether end-of-life care received after ACP actually meet their preferences.
Eight randomised controlled trials (702 women) were identified that compared withholding gonadotrophins (coasting) with another intervention to prevent ovarian hyperstimulation syndrome. The other interventions included no coasting, early unilateral follicular aspiration (taking follicles from one ovary 10 to 12 hours after the administration of human chorionic gonadotrophin (hCG)), gonadotrophin-releasing hormone (GnRH) antagonist (drugs that block the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH), and FSH co-trigger (extra dose of FSH given at the same time as the hCG). There was low-quality evidence to suggest that coasting reduced rates of moderate or severe OHSS more than no coasting. There was no evidence to suggest that coasting was more beneficial than other interventions, except that there was very low-quality evidence from a single small study to suggest that using FSH co-trigger at the time of HCG administration may be better at reducing the risk of OHSS than coasting. There were too few data to determine clearly whether there was a difference between the groups for any other outcomes. The quality of evidence was low or very low. The main limitations were failure to report live birth, risk of bias due to lack of information about study methods, and imprecision due to low event rates and lack of data. Four of the studies were published only as abstracts, and provided limited data.
We last searched for evidence in June 2018. We included only one trial conducted in Ukraine, and participants' primary cancer was colorectal (bowel) cancer in 66% of instances, but there were also people with stomach, breast, skin, and other tumours. All of them had cancer spread to the liver. In this trial, 123 participants were allocated at random to receive either cryotherapy (63 people) or conventional surgery (affected parts of the liver were removed; 60 people). The trial did not provide information on funding. The trial was at high risk of bias. The participants were followed for up to 10 years (minimum five months). The trial reported that the mortality at 10 years was 81% (51/63) in the cryotherapy group and 92% (55/60) in the conventional surgery group. We judged the evidence as low-certainty evidence. We found no evidence of a difference in proportion of participants with recurrence of the malignancy in the liver: 86% (54/63) of the participants in the cryotherapy group and 95% (57/60) of the participants in the conventional surgery group developed a new malignancy (low-certainty evidence). The frequency of reported complications was similar between the cryotherapy group and the conventional surgery group, except for postoperative pain. Both insignificant and pronounced pain were reported to be more common in the cryotherapy group while intense pain was reported to be more common in the conventional surgery group. However, it was not reported whether there was any evidence of a difference. The frequency of unwanted effects (adverse events or complications) was mostly similar in both groups, but pain intensity and frequency seemed to differ between the groups. There were no intervention-related mortality or bile leakages. The trial did not provide data on quality of life; cancer mortality, and time to progression of liver metastases. The evidence for the effectiveness of cryotherapy versus conventional surgery in people with liver metastases is of low certainty. We are uncertain about our estimate and cannot determine whether cryotherapy compared with conventional surgery is beneficial or harmful. We found no evidence for the benefits or harms of cryotherapy compared with no intervention, or versus systemic treatments.
Studies measured agitated behaviour with various scales and the reliability of the evidence for the different scales ranged from moderate to very low. Overall, we found no evidence that valproate preparations improved behaviour, or specifically, agitated behaviour. We found that valproate preparations probably had little or no effect on participants' ability to perform daily activities. We could not be sure whether they had an effect on cognition (thinking and remembering) because the reliability of the evidence was very low. We found low-reliability evidence from three studies that participants taking valproate may be more likely than those taking placebo to experience harmful effects. We could not be as certain about differences in serious harms, such as serious illness or admission to hospital, but data from two studies suggested that these may be more common in the participants taking valproate. Some of the side effects associated with valproate were sleepiness, feeling sick, being sick, watery stools, and urinary tract infections. We only identified five relatively small studies for inclusion in this review. They varied in their methods, type of medicine and its dose, duration of treatment, and scales used to make measurements. This limited our ability to pool data across studies. However, we could be moderately confident in the conclusion that valproate preparations do not improve agitated behaviour in dementia. They may also be associated with harmful effects.
We searched scientific databases for clinical trials of low-risk adults (aged 18 years and over) allocated to home (outpatient) management or hospital (inpatient) management of acute PE. The evidence is current to March 2018. We included two studies, which included a total of 453 people. We are uncertain whether, compared with inpatient treatment, outpatient treatment has an important effect on number of deaths, bleeding, recurrence of PE, and patient satisfaction because the results were imprecise and the studies did not report side effects such as haemodynamic instability (where drugs or procedures are needed to maintain a stable blood pressure), and compliance (how well people follow medical advice). The evidence from the included studies was of low quality because of imprecision in the results. This was due to there being only small numbers of people in the studies (and small numbers of events), and because we could not confirm the absence of publication bias (reports of studies where no effect was shown might not be published). Therefore, further well-conducted randomised controlled trials (where people are allocated at random to one of two or more treatment groups, one of which is a control treatment) are required before informed practice decisions can be made.
Five studies were identified up to August 2013. These studies included a total of 176 participants, with 71 people participating in water-based exercise training, 54 people participating in land-based exercise training and 51 people completing no exercise training. The average age of participants ranged from 57 to 73 years. The water-based exercise training programmes varied from four to 12 weeks in duration with attendance two to three times a week for between 35 and 90 minutes. The water-based exercises were designed to be as similar as possible to the exercises conducted in the land-based exercise sessions. The most common types of exercises were walking and cycling-type movements in the water, as well as strength training, most often using floats to increase the intensity. Participants who completed a water-based exercise training programme could walk an average of 371 metres farther than those who completed no exercise training and 313 metres farther than those who completed land-based exercise training. Quality of life also improved in participants who completed water-based exercise training, and significantly better quality of life was reported in these participants compared with those who completed no exercise training. Little information was provided to show whether these effects last for a long time after training has ceased. The effect that severity of COPD may have on benefits of water-based exercise training needs further examination. Two studies reported on adverse events; one minor adverse event was documented (from 20 people participating in water-based exercise training). The quality of evidence contributing to these results was generally low to moderate. This was mainly a result of poor study design and not enough data.
There was moderate quality evidence that hydrocortisone (a steroid medication) prevented PTSD. There was moderate quality evidence that hydrocortisone reduced the severity of PTSD symptoms. There was no evidence that propranolol (a beta-blocker), escitalopram (a type of antidepressant), temazepam (a tranquillizer) or gabapentin (an anticonvulsant) prevented PTSD. All medications were acceptable, with low numbers of people dropping out due to side effects; however not all studies provided information on this. The review authors do not feel there is sufficient evidence yet to recommend any medication as a preventative treatment for PTSD. The review authors recommend that future high quality research is needed to provide stronger evidence for the effectiveness of medications in preventing PTSD.
The review found that non-pregnant women who had two or more UTIs in the past year had less chance of having a further UTI if given a six to 12 month treatment with antibiotics. The most commonly reported side effects are digestive problems, skin rash and vaginal irritation. More research is needed determine the optimal duration for antibiotic treatment.
Most included trials were of poor quality, so their results may not be reliable. The trials were not long enough or large enough to measure whether potassium supplements reduce the risk of death, heart attack or stroke, which may be caused by high blood pressure. The studies reporting adverse effects did not find any serious side effects from taking potassium supplements. This review does not confirm whether potassium supplements can lower high blood pressure and therefore does not recommend them for treating hypertension. More trials enrolling a large number of participants with long periods of follow-up are necessary to know whether or not potassium supplements can lower high blood pressure.
The evidence on which this review is based was current as of 18 February 2019. One study involving 40 people with irreversible pulpitis (nerve damage) was included. There were two groups of 20 people, one group was treated with penicillin 500 mg, the other with placebo (no active ingredient) every six hours over a seven-day period. In addition, all of the participants received painkillers (ibuprofen and paracetamol (acetaminophen) combined with codeine).Key resultsAntibiotics do not appear to significantly reduce toothache caused by irreversible pulpitis. Furthermore, there was no difference in the total number of ibuprofen or Tylenol tablets used over the study period between both groups. The administration of penicillin does not significantly reduce the pain perception, the percussion (tapping on the tooth) perception, or the quantity of pain medication required by people with irreversible pulpitis. There was no reporting on adverse events or reactions. This was a study with a small number of participants and the certainty of the evidence for the different outcomes was rated as low. There is currently insufficient evidence to be able to decide if antibiotics help for this condition. This review highlights the need for more and better quality studies on the use of antibiotics for irreversible pulpitis.
The authors of this review included studies where healthy participants over the age of 60 years who were cognitively healthy at the start of the study were randomly assigned to receive extra omega-3 PUFA in their diet or a placebo (such as olive oil). The main outcomes of interest were new cases of dementia diagnosed during the study period, cognitive decline, side-effects, and adherence to the intervention. The authors included three randomised controlled trials involving 3536 participants. In two studies participants were randomly assigned to receive gel capsules containing omega-3 PUFA or olive or sunflower oil for six or 24 months. In the third study, participants were randomly assigned to receive tubs of margarine spread for 40 months (regular margarine versus margarine fortified with omega-3 PUFA). None of the studies examined the effect of omega-3 PUFA on new dementia cases over the study period. In two studies involving 3221 participants there was no difference between the omega-3 PUFA and placebo group in mini-mental state examination score at final follow-up. In two studies (1043 participants), other tests of cognitive function such as word learning, digit span and verbal fluency showed no beneficial effect of omega-3 PUFA supplementation. Participants in both the intervention and control groups experienced little or no cognitive decline during the studies. The main reported side-effect of omega-3 PUFA supplementation was mild gastrointestinal problems, but overall minor symptoms were reported by fewer than 15% of participants, and people in the control group were just as likely to report symptoms as those receiving an omega-3 PUFA supplement. Adherence to the supplementation protocol was high in all trials with on average over 90% of supplements being apparently consumed by trial participants. All three studies included in this review were of high methodological quality, and so the findings are unlikely to be due to chance or bias. The results of the available studies show no benefit for cognitive function with omega-3 PUFA supplementation among cognitively healthy older people. Omega-3 PUFA supplements may have other health benefits, and the authors comment that consumption of fish is recommended as part of a healthy diet. Longer studies are required, during which greater changes in cognitive function may occur, to enable researchers to identify possible benefits of omega-3 PUFA in preventing cognitive decline.
The aim of this review was to assess the effectiveness of CsA for severe UC. The literature search identified 36 studies. Only 2 studies were of high methodological quality and both support the use of CsA in UC patients with a severe attack. However, both studies were small (involving only 50 patients altogether) and limited in the length of follow-up (from a few weeks up to a year). There is limited evidence that cyclosporine is more effective than standard treatment for severe ulcerative colitis. The conclusion of the review is that while the data concerning the use of CsA in severe UC are encouraging, more studies are needed.
This review demonstrated improvements on a range of measures with the combined treatment. In the absence of significant side effects, injection of BoNT-A has been identified as a safe and effective treatment for upper limb spasticity when used in combination with occupational therapy in children with cerebral palsy.
We included five trials with 256 participants. Three trials included people experiencing a flare up of disease (171 participants) and two trials looked at long-term therapy (85 participants). We found no conclusive evidence to show that oral antibiotics were more or less effective than an alternative treatment for either flare ups of disease or long-term treatment of chronic infection with Pseudomonas aeruginosa. One of the trials with volunteers being treated for a flare up of disease reported significantly better lung function when using ciprofloxacin compared with intravenous treatment; but we did not agree with this finding when we analysed the same data. We did not find any evidence of differences between oral antibiotics and other treatments in terms of adverse events or the development of antibiotic resistance, but we do note that the trials were not designed to detect such differences. Until the results of large trials are available, people should choose their treatment on a practical basis, basing decisions on any available evidence, their clinical circumstances, the known effectiveness of drugs against local strains of the bug and individual preference. The evidence we found was limited. The trials were very different in terms of design, drugs used, length of treatment and follow up and the outcomes measured. We judged the trials to be at different risks of bias, but we did not think any of them had a low risk of bias from blinding, which might affect the results of subjective outcomes like quality of life.
We conducted a systematic search of the literature on preventing voice disorders in adults. We then appraised the quality of the studies found and combined their results. We found six studies which met our inclusion criteria. Four were conducted with teachers, one with student teachers and one with telemarketers. We found no evidence that either direct or indirect voice training nor the two combined are effective in improving vocal functioning when measured using self-reported outcomes and when compared to no intervention. All the included studies were small and of low methodological quality. Given the extent of the problem and the widespread use of voice training, further research is warranted.
A search of the major databases to July 2014 found 11 trials involving 904 participants between the ages of 18 and 85 years old, which tested the effect of exercise on acute respiratory infection symptoms. Exercise was supervised and prescribed at least five times a week, with 30 to 45 minutes of moderate-intensity activities in most studies. The number of acute respiratory infections per person per year and the severity of these symptoms were similar in the exercising and non-exercising groups. Similarly, the number of people experiencing at least one acute respiratory infection and the number of symptom days in the follow-up period were similar among people who did or did not exercise. One analysis of four trials suggested that the number of days of illness per episode of infection might be reduced by exercise. The quality of the trials was poor, which means that there might be benefit or even harm attributable to exercise. We need further studies with fewer potential biases to understand whether exercise is able to reduce the occurrence, severity or duration of acute respiratory infections.
We ran electronic searches for trials (latest search was in March 2017) for trials that randomised people with schizophrenia to receive yoga or another add-on treatment. One thousand and thirty four records were found and checked by the review authors. Six trials with 586 participants met the review requirements and provided useable data. Other add-on treatments consisted of other forms of exercise only. There is little evidence currently available, is low quality, and suggests that yoga is no more effective than other add-on treatments for schizophrenia. Current evidence from randomised controlled trials shows yoga is no more effective than other add on treatments for schizophrenia, but the only available comparators to yoga were other forms of exercise. The evidence is weak as the number of studies available was small, and only short-term follow-up was reported. More, larger, and long-term trials that compare yoga with other alternatives to exercise are therefore necessary.
The review found five trials, involving around 200 participants with this condition, which compared the clinical use of taping with no taping. All five studies differed from each other in terms of the type of participants (one trial involved army recruits), length and schedule of the treatment programme and assessment of outcome. In four trials, participants of both taping and no or placebo taping groups were prescribed exercises. In part because both the therapist and the patient knew whether they were getting taping, some caution was necessary in interpreting the study results. Pooled results from four trials (161 knees) for the level of pain at the end of the treatment programme (ranging for one week to three months) showed no difference between those given taping and those not. Data for other outcomes measuring function and activities of daily living were from single trials only and gave different results. The review concluded that the currently available evidence from trials reporting clinically relevant outcomes is and low quality and insufficient to draw conclusions on the effects of taping. However, before further trials are conducted, some consensus is required to establish the typical patients, taping technique and the best way of measuring outcome.
This review compared reduced dose (mean 60% reduction in inhaled steroid) ICS/LABA combination to either a fixed moderate/high dose ICS or a reduced/tapering ICS dose. In adults with asthma, who use moderate to high maintenance doses of ICS, the addition of LABA has an ICS-sparing effect. LABA permit a reduction of 37% (253 mcg BDP) in subjects on minimum maintenance ICS and up to 60% (300 mcg FP) in subjects on maintenance ICS without deterioration in asthma control.
In this review update, we examined 21 randomised studies that assessed the effects of low GI diets compared to diets with a similar composition but a higher GI on cardiovascular disease events and levels of cholesterol in the blood or blood pressure (major risk factors for cardiovascular disease, such as heart attacks or stroke). Studies were included up to July 2016. Participants were adults with a mean age of between 19 and 69 years. In most studies, participants had cardiovascular risk factors such as overweight or obesity or abnormal blood fat levels, and one study included participants with existing heart disease. The diets were followed for at least 12 weeks but most studies had unclear of bias and some of the compared diets only had small differences in GI. Cardiovascular disease events were not reported and no evidence of differences in effects of the diets on blood cholesterol and blood pressure were seen. Most studies did not report harms but the two that did found no harmful effects of the diets, however the evidence was poor. There was insufficient evidence from randomised controlled trials to recommend consumption of low GI diets for the purpose of improving blood lipids or blood pressure.
We searched for any randomised controlled trial comparing either codeine (or medications produced from codeine) versus placebo in the treatment of chronic cough (4 weeks or longer) in children aged 18 years and younger. The search identified 556 records. We reviewed and assessed all of these against predetermined inclusion/exclusion criteria. We found no eligible studies to include in this review. However, our search did find studies that investigated codeine (or medications produced from codeine) in the treatment of acute cough (two weeks or less) in children. Another Cochrane review specifically for children with acute cough evaluated these studies and found no evidence to support or oppose use of codeine (or medications produced from codeine). This overall lack of evidence is consistent with international chronic cough guidelines, which recommend treating the cause of the cough. Due to the known risks associated with use, in particular the increased risks for children, governing bodies in the USA, Europe, Canada, New Zealand, and Australia have stated these medications are now not recommended for children younger than 12 years of age and children between 12 to 18 years with respiratory conditions. Given the lack of supporting trials, the findings from trials of acute cough in children, and the known harmful side effects, we have concluded that codeine-based medications cannot be recommended in children with chronic cough. We found no studies and hence there is no quality of evidence.
Controlled clinical studies that evaluated the effect of systemic corticosteroids to induce remission in Crohn's disease were reviewed. For inclusion in this analysis, studies could compare any form of corticosteroid that is systemically absorbed (e.g. prednisone, prednisolone, 6-methylprednisolone or hydrocortisone) to either placebo (fake medicine) or 5-aminosalicylates (e.g. mesalazine, mesalamine or sulfasalazine). Corticosteroids were found to be more effective than either placebo or 5-aminosalicylates at inducing remission in Crohn's disease. Although corticosteroids caused side effects more often in patients compared with placebo and 5-aminosalicylates, these side effects were not serious enough to cause withdrawal from the studies reviewed. In summary, corticosteroids are effective at inducing remission in patients with Crohn's disease. While they cause frequent side effects, these side effects were relatively minor in the reviewed studies, some of which followed patients for up to 24 weeks.
This review included information from 13 randomized studies and combined results from 2122 patients to answer our question regarding survival. This review of 13 trials, including patients with esophageal cancer of any cell type, found some evidence that cisplatin-based chemotherapy may help them to live longer. However, chemotherapy may introduce side effects. This review used information from randomized studies that is considered to represent the highest quality of evidence.
Twenty-one randomised controlled studies were identified, of which 13 were included. Eight studies were excluded. The studies included a total of 750 women—406 women in the intervention groups and 344 women in the control groups. The interventions assessed included medical treatment and psychological, cognitive, behavioural, complementary and physical therapies. The evidence is current to February 2014. The review concludes that evidence shows improvement of pain in women given a high dose of progestogen (50 mg medroxyprogesterone acetate) immediately post-treatment and for up to nine months after treatment. However, progestogen was associated with adverse effects such as weight gain and bloating. Women who underwent reassurance ultrasound scans and who received counselling were more likely to report improved pain than those whose treatment involved a 'wait and see' policy. Some evidence of benefit was seen with writing disclosure therapy and with distension of painful pelvic structures. No good evidence of benefit was noted with other interventions when compared with standard care or placebo. The quality of the evidence was low or moderate for most comparisons, and in most cases evidence was derived from single small studies. Moreover, we were unable to draw meaningful conclusions on quality of life and physical and functional outcomes because of the large variation in outcome measures used by the included studies. Many interventions identified in this review involved only single studies with small sample sizes. Additional studies will be required in the future to replicate results obtained with the use of specific medical interventions.
This review identified one trial which did not show that telemedicine alters the time these infants stay in hospital. However, there was some imprecision of the published data in this study that makes it difficult to make firm recommendations either way with telemedicine.
We searched the databases until October 2013 and identified 14 studies (randomized controlled trials) with a total of 1109 participants. We reran the search on 4 February 2015 and will deal with the one study of interest when we update the review. We investigated the benefits of post-pyloric tube feeding for reducing the rate of pneumonia, decreasing the number of days that a person needs to be dependent on a breathing machine, increasing the percentage of nutrients that can be provided to the participant and reducing the number of deaths. We also investigated potential complications that may occur during insertion of the tube, such as bleeding from the gastrointestinal tract, and complications arising during maintenance of the tube, such as the need to replace the tube. We found that post-pyloric feeding appeared to reduce the rate of pneumonia and increase the amount of nutrition delivered to the patient. Its use did not result in fewer days that a person needed to be dependent on a breathing machine nor in fewer deaths. The target amount of feeding for a person fed with a post-pyloric tube was reached without delay. Insertion of a post-pyloric feeding tube appears safe and did not increase the likelihood of complications. We found evidence of moderate quality for the outcomes of rate of pneumonia, duration of dependency on a breathing machine and rate of death, mainly because identified studies were poorly conducted. With regard to the total quantity of nutrients that can be delivered to patients and complications related to insertion and maintenance of the tube, the quality of evidence was assessed as low. Evidence for the time required to reach the target amount of feeding was very low in that results were not similar across studies and study design issues hindered assessment. We recommend that a post-pyloric feeding tube should be used routinely for all ICU patients, when this approach is feasible.
We found 12 randomised controlled trials (studies where people were allocated at random to one of two or more treatment or control groups), with 1128 participants. On average, the interventions lasted about five months, while investigators followed up participants from between 4 to 52 months. Five studies took place in the USA and one each in Australia, France, Germany, India, Israel, Italy, and the Netherlands. The studies considered baclofen at different doses (ranging from 10 mg a day to 150 mg a day), and in some cases, the doses were increased during the treatment. None of the studies added other drugs or other treatments to the baclofen treatment. All the studies compared baclofen to placebo, except for one study that compared baclofen to acamprosate at a dose of 666.66 mg three times a day for three months. Compared with placebo, baclofen makes little or no difference to participants who dropped out from treatment, dropped out due to adverse events (side effects), or the number of participants with at least one adverse event. Baclofen probably makes little difference to the number of participants who start drinking again, nor to how much or how often they drink. Baclofen may make little or no difference in the percentage of days people remain alcohol-free. Baclofen may increase the amount of use measured by number of drinks per drinking days. We found that baclofen increased adverse events like depression, vertigo, somnolence, numbness and muscle rigidity but we did not find significant differences between baclofen and placebo for other adverse events. The certainty of evidence (how much we can be confident that the evidence is reliable) was high for results about the number of participants with at least one adverse event, and about people dropping out of the studies for any reason or dropping out due to adverse events. The certainty of the evidence was moderate for results about people returning to any drinking and how many heavy drinking days they had. It was low for results about drink per drinking days and percentage of days of abstinence.
Both trials assessing HDCT followed by ASCT versus conventional chemotherapy showed no significant improvement in overall survival, however progression-free survival was significantly improved with HDCT followed by ASCT. Only one trial reported adverse events and showed no difference between the treatment arms. The other trial was prematurely closed as patients refused randomisation and requested ASCT. Only one trial evaluated the effect of SHDCT before HDCT plus ASCT, compared to HDCT plus ASCT. Overall survival and progression-free survival were similar in both arms. However, after three years, there was a negative trend for the SHDCT arm regarding mortality as well as significantly increased adverse events. In summary, the currently available evidence suggests a benefit for patients with relapsed HL treated with HDCT followed by ASCT compared to conventional chemotherapy.
Tiotropium is an inhaled medication that helps open the airways (bronchodilator) and is used to manage persistent symptoms of COPD. We found seven studies including 12,223 participants that compared tiotropium with long-acting beta2-agonists (LABAs), which are another type of bronchodilator. This systematic review found that currently there is insufficient evidence to suggest which of these treatments provides greater long-term benefit in quality of life. Furthermore, both treatments had similar effects on symptoms, lung function and death rates. Tiotropium appears better than LABAs in preventing COPD exacerbations (worsening of COPD symptoms) and reducing the number of COPD-related hospitalisations. Furthermore, there were fewer participants during the study period with serious adverse events or who withdrew early from the studies with tiotropium compared with LABA treatment. However, there was no difference in the total number of people who were hospitalised. We found six economic evaluations looking at the cost and effectiveness of tiotropium and the LABA salmeterol that were conducted in the UK, Greece, Netherlands, Spain, or USA. All the studies estimated tiotropium to be better than salmeterol based on medical outcomes (exacerbations or quality of life) and/or lower total costs, including respiratory medications and hospitalisations. However, these results were very uncertain.
This is an update of a previous review. The first review was published in 2014 and included 13 studies. For this update, we searched for studies published up to January 2016 and found 11 new studies. Only two of the included studies are randomized controlled trials and followed participants for at least six months. These provide the best evidence. The remaining 22 studies either did not follow participants for very long or did not put people into treatment groups so could not directly compare ECs with something else. These studies can tell us less about how ECs might help with quitting smoking but can tell us about short-term safety. The two randomized trials, conducted in New Zealand and Italy, compared ECs with and without nicotine. We judged these studies to be at low risk of bias. In one study, people wanted to quit smoking, while in the other study they did not. The trial in people who wanted to quit smoking also compared ECs to nicotine patches. Combined results from two studies, involving 662 people, showed that using an EC containing nicotine increased the chances of stopping smoking in the long term compared to using an EC without nicotine. We could not determine if EC was better than a nicotine patch in helping people stop smoking, because the number of participants in the study was low. More studies are needed to evaluate this effect. The other studies were of lower quality, but they supported these findings. None of the studies found that smokers who used EC short- to mid-term (for two years or less) had an increased health risk compared to smokers who did not use ECs. The quality of the evidence overall is low because it is based on only a small number of studies, although these studies were well conducted. More studies of ECs are needed. Some are already underway.
Our search for studies (on 30 April 2015) identified nine randomised controlled studies involving 469 women, but only six trials (involving 383 women) contributed data towards this review. The studies included small numbers of women and were not generally of high quality. None of the included studies reported data on cervical or uterine injury, which are rare events. Cervical preparation, either using mechanical or chemical dilation with misoprostol, was shown to reduce the need for manual cervical dilatation and surgical time compared with placebo (two trials, 168 women). Misoprostol was associated with more abdominal pain than placebo but no clear differences were observed in the risk of other adverse effects such as nausea, vomiting, headache or fever. Misoprostol and isosorbide mononitrate and dinitrate were similarly effective in ripening the cervix and reducing the need for manual cervical dilation (three trials, 150 women). Misoprostol caused more vomiting but with no clear differences in other reported adverse effects (headache, nausea or hypotension). The dosing regimens differed in terms of dose, number of administrations and route of administration in the different trials. Mechanical (Dilapan-S hygroscopic) dilators performed similarly to chemical dilators in a single trial (65 women) that measured difficulty in cervical dilation, excessive bleeding and adverse effects. The medications or devices used did reduce the need for manual dilation of the cervix, but were associated with some side effects. These include abdominal pain, nausea, vomiting, fever, headache and diarrhoea. The particular agents that we compared were misoprostol, isosorbide mononitrate, isosorbide dinitrate and Dilapan-S hygroscopic dilators. No agent performed significantly better than another. The nine studies included in this review were small and the methodological quality of the trials was varied. For the most part, the study methods were not well-described; thus any conclusions drawn from the data included in this review must be treated with caution. Large, high-quality trials are required to understand whether easier dilation means there is less risk of injury to the woman's uterus or cervix during the surgery, or if there are any effects on future pregnancies.
The review found that, for people who have had a bleeding peptic ulcer caused by Helicobacter pylori, treatment with antibiotics more effectively prevents gastrointestinal re-bleeding than acid-suppressing drugs. Antibiotics when Helicobacter pylori infection is present are also cheaper and more convenient than long-term acid-suppressing drugs.
We found 26 studies that provided data from 17 countries, involving more than 15,000 women in a wide range of settings and circumstances. The continuous support was provided either by hospital staff (such as nurses or midwives), or women who were not hospital employees and had no personal relationship to the labouring woman (such as doulas or women who were provided with a modest amount of guidance on providing support). In other cases, the support came from companions of the woman's choice from her own network (such as her partner, mother, or friend). Women who received continuous labour support may be more likely to give birth 'spontaneously', i.e. give birth vaginally with neither ventouse nor forceps nor caesarean. In addition, women may be less likely to use pain medications or to have a caesarean birth, and may be more likely to be satisfied and have shorter labours. Postpartum depression could be lower in women who were supported in labour, but we cannot be sure of this due to the studies being difficult to compare (they were in different settings, with different people giving support). The babies of women who received continuous support may be less likely to have low five-minute Apgar scores (the score used when babies’ health and well-being are assessed at birth and shortly afterwards). We did not find any difference in the numbers of babies admitted to special care, and there was no difference found in whether the babies were breastfed at age eight weeks. No adverse effects of support were identified. Overall, the quality of the evidence was all low due to limitations in study design and differences between studies. Continuous support in labour may improve a number of outcomes for both mother and baby, and no adverse outcomes have been identified. Continuous support from a person who is present solely to provide support, is not a member of the woman's own network, is experienced in providing labour support, and has at least a modest amount of training (such as a doula), appears beneficial. In comparison with having no companion during labour, support from a chosen family member or friend appears to increase women's satisfaction with their experience. Future research should explore how continuous support can be best provided in different contexts.
The purpose of this review was to examine the effect of psychosocial and psychological interventions to reduce the risk of postpartum depression compared with usual care. This review includes data from 28 randomised controlled trials involving almost 17,000 women. The preventative interventions evaluated in the included trials were diverse and the end-points differed widely but the methodological quality was good to excellent. A clear beneficial effect in the prevention of postpartum depression was found from a range of psychosocial and psychological interventions. Promising interventions included professionally-based postpartum home visits, lay- or peer-based postpartum telephone support, and interpersonal psychotherapy. Interventions provided by various health professionals and lay individuals were similarly beneficial. Interventions that were individually-based were beneficial as were those that involved multiple contacts. There is also evidence that interventions initiated postnatally assisted in preventing postpartum depression as were those specifically targeting 'at-risk' mothers. Many questions remain unanswered and additional research is needed.
We considered eight studies, but none of them recruited participants solely on the basis of having antisocial personality disorder. While most studies included in this review looked at treatments to reduce drug or alcohol misuse in people with antisocial personality disorder, no study focused on treating the disorder itself. Studies varied in terms of choice of outcomes. While some studies reported outcome measures that were originally defined in the review protocol as being of particular importance in this disorder (for example, aggression, social functioning and adverse effects resulting from the use of medication), no study reported on reconviction. In summary, we were unable to draw any firm conclusions from the existing literature.  Nonetheless, there was some evidence that nortriptyline (a drug used to treat depression) could help people with antisocial personality disorder to reduce their misuse of alcohol. There was also some evidence that phenytoin (a drug used to treat epilepsy) could help to reduce the intensity of impulsive aggressive acts in people with antisocial personality disorder. Further research is required to clarify which medications are effective for treating the core features of this disorder. This research is best carried out using carefully designed clinical trials. Such trials should recruit sufficient numbers of people on the basis of having the disorder and use outcome measures that are of particular relevance to this disorder. They should also focus on recently marketed drugs where these have largely replaced older medications (for example, nortriptyline and phenytoin) which are no longer widely used.
Thirteen trials involving 2197 participants were included in this review. We found that several antibiotic treatments were equally effective in eliminating the bacteria infecting patients, but they did not alter the clinical outcome. There was insufficient evidence to decide whether there is benefit for treating healthy contacts. Side effects were reported with antibiotics and they varied from one antibiotic to another. The result of the review should be interpreted with caution since this review is based on a limited number of trials and some of these trials involved small numbers of participants.
We included two studies with a total of 210 participants in this review. Both trials were at some risk of bias because not enough care had been taken to ensure that groups received the same treatment other than the interventions being tested. One trial found some benefits from using foot orthoses over simple insoles at six weeks but not at one year. Participants wearing orthoses were, however, more likely to report minor adverse effects (e.g. rubbing, blistering) and discomfort compared with those wearing insoles. There were no important differences in knee pain and function in people given foot orthoses as well as physiotherapy when compared with people given physiotherapy only. Results for knee pain and function did not show important differences between foot orthoses versus physiotherapy. On the basis of the available evidence we do not recommend foot orthoses for adults with pain around the knee cap.
Three main models of care (case management, shared care and interdisciplinary team) designed to improve continuity of care were identified in the 51 studies included in this review. We found no standard instruments that allow to specifically measure continuity of care in patients with cancer. According to our analysis, there was no clear evidence that the interventions assessed in this review either improved or worsened patient health-related outcomes. Therefore, our analyses did not allow us to draw firm conclusions on the effectiveness of interventions designed to improve continuity of care in the follow-up of patients with cancer. Few studies reported provider and informal caregiver outcomes, as well as process of care outcomes, so they could not be regrouped for analysis. The main limitations of this review were the various differences between the included studies, especially in their study designs, interventions, participants, patients' phase of care, measured outcomes, healthcare settings, and length of follow-up. More relevant research is needed to sort out which interventions aiming to improve continuity of care in the follow-up of patients with cancer are the most beneficial to improve patient, provider and process of care outcomes. Future research should identify which outcomes are the most sensitive to change and the most meaningful regarding continuity of care. Also, it would be valuable to develop a standardised instrument to measure continuity of care in patients with cancer.
This review assesses the value of clinical symptoms and signs in helping doctors and nurses decide whether a child or young person might have a chest infection caused by M. pneumoniae. We analysed data from seven studies including a total of 1491 children, all of which were conducted in hospital settings. We found that the presence of wheeze makes M. pneumoniae slightly less likely and the presence of crepitations (i.e. crackles heard on listening to the chest) makes M. pneumoniae slightly more likely. However, these clinical features are not sufficiently helpful to guide decisions about prescribing antibiotics for possible M. pneumoniae infections. Based on the results of two studies, the presence of chest pain doubles the likelihood of M. pneumoniae. However, further research in this area is needed, particularly in general practice and outpatient populations.
Two trials tested a dressing containing ibuprofen, however, the pain measures and time frames reported were different. One trial indicated that pain relief achieved over 5 days with ibuprofen dressings could represent a clinically relevant reduction in pain. The other trial found no significant difference in the chance of pain relief, measured on the first night of treatment, for ibuprofen dressings compared with foam dressings. This trial, however, was small and participants were only followed for a few weeks, which may not be long enough to assess whether the dressing affects healing. There was evidence from five trials that a local anaesthetic cream (EMLA 5%) reduces the post-procedural pain of debriding leg ulcers but there was insufficient evidence regarding any side effects of this cream and its impact on healing.
We included in our review 11 randomized controlled trials (829 participants). These trials were conducted between 1997 and 2014 and differed with regard to participants (adults vs children), concentrations of sevoflurane used, addition of nitrous oxide and opioids and other factors. Some elements of the methods suggested low-quality evidence would be obtained. The studies could not always be combined, and study results cannot be stated with certainty. The high initial concentration technique shortened induction time (six studies, 443 participants, low-quality evidence) and led to similar rates of cough (eight studies, 589 participants, low-quality evidence), sudden sustained closure of the vocal cords that prevented breathing (seven studies, 588 participants, low-quality evidence), breath holding (five studies, 389 participants, low-quality evidence), sudden movements (five studies, 445 participants, low-quality evidence) and slow heart rate (three studies, 199 participants, low-quality evidence). The high initial concentration technique showed greater suspension of breathing when compared with the low initial concentration technique (two studies, 160 participants, low-quality evidence). The included studies provided low-quality evidence, and study results should be interpreted with caution. More studies are needed to enable firm conclusions.
In 2014, we undertook computer searches for randomised trials evaluating mobile phone-based interventions to increase contraception use. We found five trials. Three trials used text messaging to support women in continuing to use a specific method of contraception. Two trials aimed to improve both uptake and continued use of contraception - one with voice and one with text messaging. Our review provides limited evidence that interventions delivered by mobile phone improve contraception use. One trial in the USA reported that women were more likely to continue to take the contraceptive pill from an intervention comprising a range of educational text messages. One trial in Cambodia reported increased use of contraception at four months post abortion from an intervention comprising voice messages and phone counsellor support. Another trial in the USA reported improved attendance for the first but not subsequent contraceptive injection appointments from an intervention comprising reminders and healthy self management text messages. Simple text message contraceptive pill reminders did not reduce missed pills in a small trial in the USA. No difference in contraception use was reported amongst users of isotretinoin (a drug used for acne) from an intervention that provided health information via text messages and mail. In conclusion, evidence indicates that a series of voice messages and counsellor support can improve contraception amongst women seeking abortion services not wanting to get pregnant again at the current time, and data suggest that daily educational text messages can improve continued use of the contraceptive pill. However, the cost value and long-term effectiveness of these interventions remain unknown. More good quality trials are needed to establish the effectiveness of interventions delivered by mobile phone to increase contraception use.
The aim of this review was to determine the extent to which spironolactone reduces blood pressure, the nature of spironolactone’s adverse effect profile, and to determine the clinical impact of its use for hypertension. The search revealed 5 cross-over trials with a total of 137 patients that received both spironolactone followed by placebo or vice verse, in a random order. One other trial was found that randomly gave 42 patients either spironolactone (22 patients) or placebo (20 patients). The daily doses of spironolactone used in these studies ranged from 25-500 mg daily. Studies followed patients for 4 to 8 weeks of therapy. None of the studies reported on the clinical impact of spironolactone (i.e. whether spironolactone reduced heart attacks or strokes compared to placebo). Overall reporting of adverse effects was poor so no conclusions can be drawn about the adverse effect profile. This meta-analysis shows that spironolactone reduces systolic/diastolic blood pressure by approximately 20/7 mm Hg compared to placebo.
The review authors found 26 randomised and quasi-randomised controlled studies evaluating the impact of community-based intervention packages for the prevention of maternal illness and death and in improving newborn health outcomes. These studies were mostly conducted in developing countries (India, Bangladesh, Pakistan, Nepal, China, Zambia, Malawi, Tanzania, South Africa, Ghana) with one additional study in Greece. Women in areas assigned to receive a community-based intervention package and with health workers receiving additional training had less illness and fewer complications during pregnancy and birth and there were fewer stillbirths, infant deaths around the time of birth and maternal ill-health. Community-based intervention packages were associated with improved uptake of tetanus immunisation, usage of clean delivery kits for home births and institutional deliveries. They also improved early initiation of breastfeeding and health-care seeking (by the mothers) for illnesses related to (their) babies. Whether these translate into improved newborn outcomes is unclear. This review highlights the value of integrating maternal and newborn care in community settings through a range of interventions which can be packaged effectively for delivery through a range of community health workers and health promotion groups. There is sufficient evidence to scale up community-based care through packages which can be delivered by a range of community-based workers. Most of the reviewed studies did not document the complete description and characteristics of the community health workers, especially the initial level of education and training, the level and amount of supervision provided, and the community ownership of these workers. This information would be of great relevance to policy and practice.
We included four studies in our review (278 participants). The studies were conducted between 2003 and 2010. Although all four included studies were randomized, some elements of their methodology suggest a low to unclear risk of bias in all trials. We found that propofol did not reduce measured overall blood loss in either children or adults (2 studies; 158 participants). Propofol might improve the quality of the surgical field a little (4 studies; 277 participants), but there was no difference in operation time (3 studies; 214 participants). Propofol was more reliable in achieving induced hypotension (1 study; 88 participants). No studies reported any adverse effects from induced hypotension with propofol. We found only four studies, which included a small total number of participants. The evidence from the studies were of moderate to very low quality, and therefore our results should be interpreted with caution. More studies are needed to confirm whether any important benefit is associated with the use of propofol.
This review aimed to find out if cognitive-behavioural approaches (CBT) help reduce the negative impact of sexual abuse on children. Ten studies, in which a total of 847 children participated, met the inclusion criteria for the review. The reporting of studies was poor, and there appear to be significant weaknesses in study quality. The evidence suggests that CBT may have a positive impact on the effects of child sexual abuse, including depression, post-traumatic stress and anxiety, but the results were generally modest. Implications for practice and further research are noted.
We found evidence showing that antidepressants are better than placebo in terms of effectiveness and number of people leaving the study early. However, our findings also showed that antidepressants are less well tolerated than placebo, producing more dropouts due to adverse effects. Results are limited in the following ways: some studies were funded by pharmaceutical companies, and only short-term outcomes were assessed. We found almost no data on other clinically relevant outcomes, such as functioning and quality of life. The quality of the available evidence ranged from very low to high. Studies with outcomes assessed at longer-term follow-up visits should be carried out to establish whether the effect is transient or maintained. Trials should better report any harms experienced by participants during the trial. In addition, a further analysis with an approach called 'network meta-analysis' will include all psychopharmacological treatments available for panic disorder, and will likely shed further light on this compelling issue, also being able to provide more information with regard to comparative efficacy of different available interventions.
Twelve studies of variable quality were identified that included a total of 1149 participants. There was high heterogeneity among studies for design, methods, and blinding of investigators. Most of the studies assessed the impact of renal denervation on surrogate (e.g. blood pressure control), rather than patient-centred outcomes (e.g. mortality or quality of life). Overall, there was no evidence of benefits of renal denervation over standard treatment on cardiovascular morbidity and mortality. Similarly, renal denervation had no tangible effects on blood pressure control and renal function. However, it was associated with an increased risk of episodes of bradycardia (very slow heart rate). The quality of the evidence was low for cardiovascular morbidity and adverse events and moderate for lack of effect on blood pressure and renal function. The evidence is current to 17 February 2016. Current evidence is inconclusive to support the use of renal denervation to improve cardiovascular and renal risk and blood pressure control in patients with resistant hypertension. Future studies targeting patient-centred outcomes, with longer duration and larger number of participants are needed to identify whether individuals can benefit from this procedure.
The review with nine randomised controlled trials (1233 patients, 622 with stapling and 611 with the handsewing technique) compared the safety and effectiveness of stapled versus handsewn colorectal anastomosis surgery. Meta-analysis was performed using the risk difference and weighted mean difference, with corresponding 95% confidence intervals. Outcome measures were mortality, anastomotic dehiscence, narrowing (stricture), haemorrhage, need for reoperation, wound infection, anastomosis duration (time taken to perform the anastomosis) and hospital stay. No significant statistical differences were found except that stricture was more frequent with stapling (P < 0.05) and the time taken to perform the anastomosis was longer with handsewn techniques.
This review (five studies involving a total of 446 people) suggests that hydrogel dressings may be more effective than basic wound contact dressings in healing foot ulcers in people with diabetes although the original research may be biased. There is insufficient research comparing hydrogel with advanced dressing types to allow conclusions to be drawn regarding relative effectiveness in terms of ulcer healing.
We searched electronic databases up to February 2011, as well as trial registers, conference proceedings and reference lists of articles, for studies comparing diagnostic tests for people with suspected rotator cuff tears. Our review included 20 studies (1147 shoulders). Many studies had design flaws, which limited the reliability of their findings. We found that MRI, MRA and US may have similar accuracy for detecting the presence of full thickness tears. For identifying any tears (no distinction between partial or full thickness) or identifying partial thickness tears, MRI and US may also have similar accuracy. However, it appears that compared with US, MRI may be more sensitive in identifying partial thickness tears. With these results we can conclude that all three imaging tests (MRI, MRA and US) may help decisions regarding referral for surgery for people with suspected full thickness tears. Information on adverse effects of using these tests was not reported by the included studies.
Carbamazepine was developed to treat epilepsy, but it is now used to treat various forms of chronic pain. We performed searches (up to February 2014) to look for clinical trials where carbamazepine was used to treat neuropathic pain or fibromyalgia. We found 10 studies involving 418 people involved in testing carbamazepine. Studies were not generally of very good quality. Most were very small, as well as of short duration. Studies lasting only one or two weeks are unhelpful when pain can last for years. There was not enough good quality evidence to say how well carbamazepine worked in any neuropathic pain condition. Pooling four small studies showed that it was better than placebo, but the result cannot be relied upon. There was not enough information from these studies to make any reliable comment on adverse events or harm. Carbamazepine is probably helpful for some people with chronic neuropathic pain. It is not possible to know beforehand who will benefit and who will not.
We included eight randomised studies (clinical studies where people are randomly put into one of two or more treatment groups) with 1699 participants. Five trials compared the scheduled use of phosphodiesterase inhibitors (a type of medicine) to either no treatment or a placebo (a pretend drug with no effect). Two studies compared the use of phosphodiesterase inhibitors either as a daily prescription or as needed. One study compared the daily use of either a phosphodiesterase inhibitor or a medicine called prostaglandin E1 that is placed into the tip of the penis like a suppository. The main outcomes of this review that we felt were most important to men were how good they thought their erections were (self-reported potency), how good their erections were based on a specialised erection questionnaire (quality of erections) and any whether there were any major unwanted side effects. We found that the men who used these medicines on a scheduled basis may have had similar self-reported erections and quality of erections (based on questionnaires they filled out) as men who took no medication regularly or use it as needed. They also had similar rates of serious unwanted side effects and similar rates of stopping the drug before the end of the treatment duration. However, we are very uncertain of these findings. We were unable to research whether these results would be different in different groups of men based on whether the surgeon tried to preserve the nerves that help with erections or not, based on men's age and how good their erections were beforehand because we found no studies. The quality of evidence was very low for most main outcomes. That means we are very uncertain of the results of this review. Further research will likely change these findings.
The evidence is current to October 2017. We included four randomized controlled studies (clinical studies where people are randomly put into one of two or more treatment groups) with 149 participants in the review. Two studies are awaiting classification (because we could not assess their eligibility) and one study is ongoing. All participants were critically ill and were in the ICU. We did not combine the results from the studies because of differences in comparison (called control) treatments and study design. One study compared propofol with no agent. This study used polysomnography (which records brain waves, oxygen level in blood, heart rate, breathing, and eye and leg movements) to measure sleep quality and quantity. It reported no improvement in duration of sleep with propofol but participants woke up less often and for shorter lengths of time and described their sleep quality as being improved with propofol. One study compared a higher dose of propofol at night described as additional night sedation, with a constant day-time and night-time dose. This study used the Ramsay Sedation Scale (which is normally used by anaesthetists to assess how easily a person is roused) and reported that participants appeared to have an improved sleep rhythm. Two studies compared propofol with benzodiazepines (a tranquilizing medicine; flunitrazepam in one study and midazolam in one study). These studies used the Pittsburgh Sleep Diary and the Hospital Anxiety and Depression Scale to measure quantity and quality of sleep. The study with flunitrazepam reported fewer awakenings of reduced duration with propofol but similar total sleep time in each group and the study with midazolam reported no difference in sleep quality. The study with flunitrazepam also measured sleep with Bispectral Index (used by anaesthetists to assess depth of anaesthesia) and reported longer time in deep sleep, with fewer awakenings. The study with midazolam reported higher levels of anxiety and depression in both groups, and no difference when participants were given propofol. No study reported on side effects. We judged the evidence to be very low quality. We found only four small randomized controlled studies and the results of the studies were not consistent. We noted differences in illness severity of participants and the medicines that were compared with propofol in the included studies. Measuring quality of sleep using diaries, questionnaires and scoring systems is based on, or is influenced by, personal feelings or opinions, and we were concerned that staff and participants were aware which medicine they had been given; we believed that this could have influenced the results. Only one study used polysomnography, which is the most appropriate unbiased measurement tool for sleep. We were unable to collect sufficient evidence to determine whether propofol given at night to adults in the ICU improves quality and quantity of their sleep, as a way of helping recovery.
Many of the studies had substantial limitations. Generally, the studies done to date do not support the routine use of oximes, however, they cannot exclude that there would be some doses or situations where a benefit would occur. The reviewers found that not enough research has been done to see whether oximes are actually effective or to define the doses that are more likely to be helpful. More research is needed before any firm conclusions can be drawn.
This systematic review was aimed at determining whether any cardiopulmonary intervention (interventions that change the circulation or breathing during surgery) decreased blood loss or decreased allogeneic blood transfusion requirements in patients undergoing liver resections. This review included 10 trials with 617 patients. All trials had high risk of bias (with the possibility of overestimating the benefits and underestimating the harms of the treatment) and play of chance ('random error'). The interventions included low central venous pressure (CVP; lowering the pressure in the major veins), autologous blood donation (using the patient's own blood obtained prior to liver resection), haemodilution (replacing blood with other fluids), haemodilution with controlled hypotension (lowering the blood pressure in addition to diluting the blood), and hypoventilation (decreasing the rate of artificial breathing). They were compared with controls not receiving the interventions. There were no differences in the number of deaths or complications due to surgery in any of the comparisons. Long-term survival was not reported in any of the trials. Fewer patients required transfusion of blood donated by others when haemodilution or haemodilution with controlled hypotension were compared with a control group. The other comparisons did not decrease the transfusion requirements. However, there is a high risk of type I errors (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included and the small sample size in each trial, as well as the inherent risk of bias (systematic errors which can result in overestimation of the benefits and underestimation of the harms of the intervention). Haemodilution showed promise in the reduction of blood transfusion requirements in patients undergoing liver resections. Further randomised clinical trials with low risk of bias (systematic errors) and low risk of play of chance (random errors) which assess clinically important outcomes (such as death and complications due to the operation) are necessary to assess cardiopulmonary interventions aimed at decreasing blood loss in liver resections. Trials need to be designed to assess the effect of a combination of different interventions during liver resections.
The authors identified 12 trials that met their inclusion criteria, with a total of 1283 children under 5 years; of these, 1226 were used in the analysis (724 given early refeeding; 502 given late refeeding). There was no significant difference between the two refeeding groups in the number of participants who needed unscheduled intravenous fluids (813 participants, 6 trials), who experienced episodes of vomiting (466 participants, 5 trials), and who developed persistent diarrhoea i.e. greater than 14 days in duration (522 participants, 4 trials). The mean length of hospital stay was also similar (246 participants, 2 trials).There is therefore no evidence to suggest that early refeeding increases the risk of complications after acute diarrhoea such as the need for IV fluids, or increases the risk of developing persistent diarrhoea. Further studies are needed to fully examine other parameters such as duration of diarrhoea, and effect on weight gain.
The evidence is current to June 2015. Three small randomised controlled trials (RCTs) enrolling 79 participants were included in the review. All studies included children younger than 2.5 years with a diagnosis of bronchiolitis who required mechanical ventilation. Two studies did not include a placebo (a substance having no active effect) for comparison. None of the included studies provided a source of funding. Two included studies reported no mortality. Use of surfactant for mechanically ventilated infants and children with bronchiolitis did not decrease the duration of mechanical ventilation. However, the intervention decreased duration of stay in the intensive care unit and had favourable effects on oxygenation and carbon dioxide removal. No complications were observed in any of the three included studies. The level of evidence for duration of mechanical ventilation, duration of intensive care unit stay, oxygenation parameters, and carbon dioxide parameters was of moderate quality. The limited number of studies with small numbers of participants was the reason for moderate quality, and are limitations of this review. There is a need for larger trials to establish any benefits of surfactant for bronchiolitis in critically ill infants and children.
A total of 16 studies were included. All studies reported on TAUS and EUS as separate tests and did not use a combination of TAUS and EUS. Six studies (16,260 participants) used TAUS for diagnosis of gallbladder polyps. No studies on the diagnosis of gallbladder polyps by EUS were found. Six studies (1,078 participants) used TAUS and three studies (209 participants) used EUS for differentiating between true and pseudo polyps. Four studies (1,009 participants) used TAUS and three studies (351 participants) used EUS for differentiating between (pre)cancerous and benign polyps. In a general population of 1000 people (in which 6.4% have a gallbladder polyp), TAUS will overdiagnose 37 people without a polyp as having a polyp, and in 7 people with a polyp, the polyp will be missed. In a population of 1000 people with a gallbladder polyp, of which 10% have a true polyp, 189 people with a pseudo polyp will be indicated as having a true polyp by TAUS, and 90 people by EUS. These people may be treated, which is not necessary. In 32 people, the true polyp will be misclassified as a pseudo polyp by TAUS and in 15 people by EUS. These people would not be treated, while they may need treatment. In a population of 1000 people with a gallbladder polyp, of which 5% have a (pre)cancerous polyp, 105 people with a benign polyp will be indicated as having a (pre)cancerous polyp by TAUS, and 75 people by EUS. These people may be overtreated for a (precursor of) cancer, which is not there. In 11 people, the (pre)cancerous polyp will be misclassified as a benign polyp by TAUS, and in 7 people by EUS. These participants may not receive proper treatment for their (precursor of) cancer. TAUS will correctly diagnose 956 out of 1000 people regarding the presence or absence of gallbladder polyps. For differentiating between polyp types, fewer people will be correctly diagnosed by TAUS, leading to unnecessary treatment for pseudo polyps and neglect of (pre)cancerous polyps. There was insufficient evidence that EUS is better than TAUS in differentiating between true and pseudo polyps and between (pre)cancerous and benign polyps. All studies were either at high or unclear risk of bias and 13 studies had either high or unclear applicability concerns. This may undermine the validity of the studies. Further studies of high methodological quality and with clearly reported criteria for diagnosis of gallbladder polyps, true polyps, and (pre)cancerous polyps are necessary.
In July 2015 we searched for studies which tested combinations of behavioural support and medication to help smokers to stop compared to usual care or brief behavioural support. People who smoked were recruited mainly in health care settings. Some trials only enrolled people who said they wanted to try to quit at that time, but some included people who weren't planning to quit. Studies had to report how many people had stopped smoking after at least six months. We found 53 studies with a total of over 25,000 participants. One very large study found a large benefit. It gave intensive support including nicotine gum, multiple group sessions, and long term contact to help people stay quit or encourage additional quit attempts. Because it was not typical of most treatment programmes, it was not included when we estimated the likely benefit, although it shows that such intensive support can be very effective. Based on the remaining 52 studies, we found high quality evidence that using a combination of behavioural support and medication increases the chances of successfully quitting after at least six months. Combining the results suggests that the chance of success is increased by 70 to 100 percent compared to just brief advice or support. There was some evidence that the effect tended to be larger when participants were recruited in healthcare settings. There was no clear evidence that providing more contact increased the number of people who quit smoking at six months or longer. .
We found six randomised controlled trials, including 708 women. Two studies compared IUI and ICI in natural cycles. Two studies compared IUI and ICI in gonadotrophin-stimulated cycles. Two studies compared the timing of IUI and ICI. The evidence is current to December 2017. There was insufficient evidence to determine whether there was any clear difference between IUI and ICI in live birth rates, in either natural cycles or in gonadotrophin-stimulated cycles. As there was only one live birth in the small study using natural cycles, we could not make any meaningful comparison between the groups. The evidence on gonadotrophin-stimulated cycles suggested that if the live birth rate following ICI was assumed to be 30%, the chance of live birth rate following IUI in gonadotrophin-stimulated cycles would be between 24% and 80%. For IUI and ICI in natural cycles, no multiple pregnancies were reported. In gonadotrophin-stimulated cycles, IUI was associated with higher multiple pregnancy rates than ICI. The evidence suggested that if the risk of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was assumed to be 10%, the risk of multiple pregnancy following IUI would be between 10% and 46%. We concluded that the evidence was too limited to encourage or discourage either IUI or ICI, in natural cycles or with ovarian stimulation in donor sperm treatment. Following GRADE assessment, we found that the evidence for all outcomes was of very low quality. The main limitations were risk of bias, due to poor reporting of study methods, and serious imprecision, due to the limited number of studies and small study sizes.
We undertook this review to try to determine which combination/s of drugs are the most effective for the first-line drug treatment of high-risk GTN, and with the least side effects. We found only one small, older study that compared a drug combination abbreviated as CHAMOCA with one called MAC. The CHAMOCA regimen, which is no longer recommended for GTN treatment, was found to be extremely toxic to the blood and bone marrow, with no greater effect against the cancer than the MAC regimen. Based on the available evidence, it is currently not possible to determine whether EMA/CO is the most effective and least toxic drug combination as no high-quality studies have been conducted comparing this combination with other combinations. GTN is a rare cancer and so studies in this field are difficult to conduct, therefore researchers need to collaborate in order to produce the necessary high-quality evidence.
We found 58 studies, which included more than one million adults, teenagers and children. Most studies lasted about one year, and were done in schools, stores or restaurants. Some studies used methods that are not very reliable. For example, in some studies participants were simply asked how much SSB they drank, which is not very reliable, as people sometimes forget how much SSB they drank. Some of the findings of our review may therefore change when more and better studies become available. We have found some evidence that some of the measures implemented to help people drink fewer SSBs have been successful, including the following: ▪ Labels which are easy to understand, such as traffic-light labels, and labels which rate the healthfulness of beverages with stars or numbers. ▪ Limits to the availability of SSB in schools (e.g. replacing SSBs with water in school cafeterias). ▪ Price increases on SSBs in restaurants, stores and leisure centres. ▪ Children’s menus in chain restaurants which include healthier beverages as their standard beverage. ▪ Promotion of healthier beverages in supermarkets. ▪ Government food benefits (e.g. food stamps) which cannot be used to buy SSBs. ▪ Community campaigns focused on SSBs. ▪ Measures that improve the availability of low-calorie beverages at home, e.g. through home deliveries of bottled water and diet beverages. We have also found some evidence that improved availability of drinking water and diet beverages at home can help people lose weight. There are also other measures which may influence how much SSB people drink, but for these the available evidence is less certain. Some, but not all studies found that such measures can have effects which were not intended and which may be negative. Some studies reported that profits of stores and restaurants decreased when the measures were implemented, but other studies showed that profits increased or stayed the same. Children who get free drinking water in schools may drink less milk. Some studies reported that people were unhappy with the measures. We also looked at studies on sugar-sweetened milk. We found that small prizes for children who chose plain milk in their school cafeteria, as well as emoticon labels, may help children drink less sugar-sweetened milk. However, this may also drive up the share of milk which is wasted because children choose but do not drink it. Our review shows that measures which change the environment in which people make beverage choices can help people drink less SSB. Based on our findings we suggest that such measures may be used more widely. Government officials, business people and health professionals implementing such measures should work together with researchers to find out more about their effects in the short and long term.
We identified four trials that tested treatments based on Xiongshao capsule. Two trials compared Xiongshao capsule plus conventional western medicine with the same conventional western medicine plus placebo; the other two trials compared Xiongshao capsule plus conventional western medicine with the same conventional western medicine alone for preventing restenosis after a PCI procedure in CHD patients. These trials reported that use of Xiongshao capsule caused a significant reduction in the incidence rates of restenosis, recurrence angina pectoris, and serious cardiovascular adverse events with no substantive adverse effects following a PCI procedure. Therefore Xiongshao capsule may represent a choice for the prevention of in-stent restenosis following a PCI procedure. However, although summary estimates indicate a protective effect of Xiongshao on restenosis, evidence is derived in part from small randomised trials, all conducted in China, with some methodological limitations that undermine the validity of the findings. Additional high-quality research trials with sufficient sample size are required.
The evidence is current to March 2016. We found 10 clinical trials evaluating these two types of bupivacaine, involving 614 women. The studies assessed the following effects of the two types of medicine: women needing to switch to general anaesthesia, additional drugs for pain relief or low blood pressure, experiencing nausea and vomiting, headache and excessive numbness. We found that all the studies had been done properly. None of them reported their source of funding. We await responses from the authors of two more studies, and will cover these when we next update the review. We found that there is insufficient evidence to establish whether denser or normal bupivacaine is the more effective in reducing the need for: a) switching to general anaesthesia; b) additional pain relief medication. Denser bupivacaine had a more rapid onset of pain relief. Due to the differences among the included studies in doses given, variety of additional drugs used for pain relief, variation in regional anaesthesia techniques and the small numbers of participants, we rated the overall quality of evidence for different outcomes from very low to moderate, as very few women experienced untoward events in all trials. We conclude that the denser form provides faster pain relief than the normal one. More research is required to be certain about the effectiveness of the denser form for other outcomes.
We searched the medical literature until 24 February 2017. We included one study with 541 study participants that randomly assigned participants with localised tumours of the kidney that were thought to be cancerous. On average, participants were followed for 9.3 years. Participants who had only the tumour taken out appear to be more likely to die from any cause than participants that had the tumour and the whole kidney taken out. There appeared to be little to no difference in the time until the tumour comes back or in the risk of serious complications resulting in death. We did not find any evidence as to how the groups compared when it comes to the need for haemodialysis or how their quality of life compared. The quality of evidence was low. This means that we have limited confidence in the results and that the true effect of partial nephrectomy may be substantially different.
Evidence in this review is current to May 2017. We found 19 studies recruiting 6461 adults. These studies assessed the effects of higher compared to lower omega-6 fat intake on heart and circulatory diseases as well as deaths. We found that three trials were highly trustworthy (with good designs that produce reliable evidence). Studies took place in North America, Asia, Europe and Australia, and eight were funded only by national or charitable agencies. Participants increased their omega-6 fats or maintained their usual fats for at least one year and up to eight years. We found that increasing omega-6 fats may make little or no difference to deaths or cardiovascular events but may reduce risk of heart attacks (low-quality evidence). Evidence was weakened by study design problems, small numbers of events, low numbers of participants from developing countries, and few women. Evidence suggests that increasing omega-6 fats reduces blood cholesterol (high-quality evidence), probably has little or no effect on body weight adjusted for height (all moderate-quality evidence), and may make little or no difference to triglycerides, high-density lipoprotein (HDL, the 'good' cholesterol) or low-density lipoprotein (LDL, the 'bad' cholesterol, low-quality evidence).
They are out-patient facilities which older patients attend for a full or near full day and receive multidisciplinary health care ‘under one roof.’ Sixteen trials involving 3689 participants were included in this review and compared day hospitals with other comprehensive services (including inpatient and outpatient services), home based care and no comprehensive services. Attendance at a day hospital offers benefits compared to providing no treatment which include reducing the risk of needing more help with daily activities such as washing or dressing. Furthermore, patients are less likely to suffer one of the following: dying, being institutionalised or becoming more dependent on others. There is no apparent benefit when day hospitals are compared with other comprehensive services or home care. The economic value of day hospitals when compared with other health care services remains unclear.
This review identified nine studies (3345 women) treated with oestrogens versus placebo, no treatment or antibiotics. Vaginal oestrogens reduced the number of UTIs when compared to placebo. All studies reported adverse events for the oestrogen treatment groups. These included breast tenderness, vaginal bleeding or spotting, vaginal discharge, vaginal irritation, burning and itching.
After her baby is born, the woman's womb (uterus) contracts and bleeding decreases. If the womb does not contract, postpartum haemorrhage (heavy bleeding) can occur, which can be life threatening. A prostaglandin, oxytocin and ergometrine are all drugs that cause contractions of the womb (uterotonics). This review of 72 randomised controlled trials, involving 52,678 women, found that oral or sublingual prostaglandin (misoprostol) is effective in reducing severe haemorrhage after giving birth and the need for blood transfusions. Misoprostol is not as effective as oxytocin and has more side-effects. The main side-effects are shivering, high temperature and diarrhoea, occurring in a significant proportion of women. Twenty-six of the trials included centres in low- and middle-income countries only. Misoprostol may be useful in places where injectable uterotonics are not available, perhaps because of poor access to skilled healthcare providers. Injectable prostaglandin may be effective in reducing blood loss but has adverse effects of vomiting, abdominal pain and diarrhoea and costs more.
In this review, we focused on third wave CBT approaches, a group of psychological therapies that target the process of thoughts (rather than their content, as in CBT), helping people to become aware of their thoughts and to accept them in a non-judgemental way. The aim of the review was to find out whether third wave CBT was effective and acceptable to people in the acute phase of depression. The review included four studies, involving a total of 224 people. The studies examined three different forms of third wave CBT, consisting of extended behavioural activation (two studies), acceptance and commitment therapy (ACT) (one study) and another form of third wave CBT called competitive mind training (one study). Three of the studies compared third wave CBT approaches with treatment as usual control conditions. The fourth study compared ACT with a psychological placebo condition. The results suggested that third wave CBT approaches were effective on a short-term basis in treating depression. However, the quality of evidence was very low because of the small number of studies/participants included in the review, together with the diverse client groups, interventions and control conditions used and possible allegiance of researchers towards the active treatments, making it difficult to draw conclusions with any confidence. It is notable, too, that none of the studies looked at the long-term effect of third wave CBT approaches. Given the increasing popularity of third wave CBT approaches in clinical practice, further well-designed studies should be prioritised to establish whether third wave CBT approaches are helpful in treating people with acute depression.
We searched for relevant studies in January 2019, and found seven studies including 1774 people. Three studies took place in the UK, and one each in Australia, United States, Qatar, and Italy. Each study provided face-to-face behavioural support delivered by pharmacy staff, who received specific training. Studies compared the structured programme to less intensive support to stop smoking. We found evidence that more intensive structured care given by community pharmacy staff probably helps more people to quit smoking than less intensive support to quit. We found low-quality evidence that community pharmacy support helps people to quit smoking. Limitations of the evidence came from potential problems with the ways some of the studies were carried out and the low numbers of people who quit smoking across the included studies, which means we are not sure how effective these programmes really are.
This updated systematic review, including 633 participants in three randomised controlled trials, suggests that omentoplasty could reduce the incidence of anastomotic leakage and the duration of hospital stay after operation. Although the difference in anastomotic leakage was significant only among patients undergoing THE, the risk ratios of omentoplasty for THE and TTE were similar. In addition, omentoplasty does not appear to increase or decrease hospital mortality nor the incidence of postoperative complications, such as anastomotic stricture, pulmonary and cardiac complications, infection, vocal cord palsy and perijejunostomy leakage. Additional clinical trials are needed to investigate the influences of omentoplasty on the incidence of anastomotic leakage and anastomotic stricture, long-term survival, duration of hospital stay and quality of life after oesophagectomy and oesophagogastrostomy when different surgical approaches are used.
The review assessed whether antiviral drugs given to pregnant women with herpes before a recurrence might be effective in reducing transmission to the baby. Seven studies were identified involving 1249 women. Giving antiviral drugs reduces viral shedding and recurrences at labor and birth. They also reduced the use of cesarean, but there is no evidence of reduction in neonatal herpes. Women should also be informed that the risk of the baby getting herpes during birth is low.
We found 12 studies that explored whether or not checking reference lists was useful for systematic reviews. These studies reported a range of results, from identifying only a few additional studies (2.5%: 2 of 79 included studies) to identifying many additional studies (42.7%: 111 of 260 included studies) through checking reference lists. Unfortunately, none of the studies looked at how much time or money were spent on the process of checking reference lists, and it was suggested this would be almost impossible to estimate. Unfortunately our findings are based on weak information. The data do suggest that in situations where researchers may have difficulty locating information, checking through the reference lists may be an important way to reduce the risk of missing relevant information.
We identified nine trials that compared fewer-than-four-ports laparoscopic cholecystectomy with four-port laparoscopic cholecystectomy. In these nine studies, 855 participants were included. Four hundred and twenty seven participants underwent fewer-than-four-ports laparoscopic cholecystectomy while the remaining 428 participants underwent four-port laparoscopic cholecystectomy. The choice of the treatment that the participants received was determined by a method similar to toss of a coin so that the two treatments were given to participants with similar characteristics. Most of these studies included low anaesthetic risk patients undergoing planned laparoscopic cholecystectomy. Fewer-than-four-ports laparoscopic cholecystectomy could be completed successfully in more than 90% of participants in most of the trials. The remaining participants were mostly converted to four-port laparoscopic cholecystectomy but some participants had to undergo open cholecystectomy (through a large incision in the abdomen). There was no mortality in either group in the seven trials that reported mortality (634 participants in the two groups). There was no significant difference in the proportion of participants who developed serious complications, quality of life between 10 and 30 days after operation, proportion of participants in whom the laparoscopic operation had to be converted to open cholecystectomy, or in the length of hospital stay between the groups. Fewer-than-four-ports laparoscopic cholecystectomy took about 15 minutes longer to complete than four-port laparoscopic cholecystectomy. The time taken to return to normal activity was one day shorter and time taken to return to work two days shorter in the fewer-than-four-ports group compared with four-port laparoscopic cholecystectomy. There was no significant difference in the cosmetic appearance between the two groups at 6 to 12 months after surgery. There appears to be no advantage of fewer-than-four-ports laparoscopic cholecystectomy in terms of decreasing surgical complications, hospital stay, or in improving quality of life and cosmetic appearance. In contrast, the safety of fewer-than-four port laparoscopic cholecystectomy is yet to be established. Fewer-than-four-ports laparoscopic cholecystectomy cannot be recommended routinely outside well-designed clinical trials. Most of the trials were of high risk of bias, that is, there is possibility of arriving at wrong conclusions because of the way that the trial was conducted. The overall quality of evidence was very low. Further well-designed randomised clinical trials (which have low probability to arrive at wrong conclusions because of chance and because of participant or researcher prejudice) are necessary to determine whether fewer-than-four-ports laparoscopic cholecystectomy is safe and whether there is any advantage of fewer-than-four-ports laparoscopic cholecystectomy over four-port laparoscopic cholecystectomy.
Randomised controlled trials (RCTs) are needed to provide robust evidence of the relative efficacy and safety of treatments. In many RCTs, clinicians (i.e. healthcare professionals inviting patients to take part in an RCT in which they provide at least one of the interventions) only invite a small proportion of the people who are eligible for trials to take part. Observational studies have been conducted to explore reasons for this but the results do not identify any factors that appear to have a consistent impact on recruitment.
The primary aim of this review is to evaluate the effects, on labour and birth outcomes, of care in an alternative institutional birth setting compared with care in a conventional hospital labour ward. We included ten trials involving 11,795 women. We found no trials of freestanding birth centres. When compared to conventional institutional settings, alternative settings were associated with reduced likelihood of medical interventions, increased likelihood of spontaneous vaginal birth, increased maternal satisfaction, and greater likelihood of continued breastfeeding at one to two months postpartum, with no apparent risks to mother or baby. Unfortunately, in several trials, the design features of the alternative setting were confounded by differences in the organizational models of care (including separate staff and more continuity of caregiver in the alternative setting), and thus it is not possible to draw conclusions about the independent effects of the design of the birth environment. We conclude that women and policy makers should be informed about the benefits of institutional settings which focus on supporting normal labour and birth.
This review includes 51 studies of over 22,000 people who smoked tobacco. Most were adults, and people typically smoked at least 23 cigarettes a day at the start of the studies. All studies included at least one group of people who were asked to cut down their smoking and then quit tobacco smoking altogether. This group was compared to either a group who did not receive any treatment to stop smoking, a group who were asked to stop smoking all at once, or a group who were also asked to cut down their smoking in a different way. We did not include studies which asked people to cut down without quitting. Studies lasted for at least six months. The evidence is up to date to October 2018. There was not enough information available to decide whether cutting down before quitting helped more people to stop smoking than no stop-smoking treatment. However, people who were asked to stop smoking all of their cigarettes at once were not more likely to quit than people who were asked to cut down their smoking before quitting. This suggests that asking people to cut down their smoking first may be a useful way to help people to stop smoking. People who cut down their smoking while using varenicline or a fast-acting form of nicotine replacement therapy (NRT), such as gum or lozenge, may be more likely to quit smoking than people who cut down their smoking without using a medicine to help them. Giving people face-to-face support to cut down their smoking may help more people to quit than if they are provided with self-help materials to cut down by themselves. There was not enough information available to decide whether other features of the cutting-down-to-quit intervention improved people's chances of stopping smoking. We looked at whether being asked to cut down smoking before quitting resulted in negative effects, such as cigarette cravings, difficulty sleeping, low mood or irritability. Most studies did not provide information about this; more studies are therefore needed to answer this question. There is very low-quality evidence looking at whether cutting down smoking before quitting helps more people to quit smoking than no treatment. We rated the quality as very low, as there were problems with the design of studies, findings of studies were very different from one another, and not enough people took part, making it difficult to tell whether cutting down helps people to quit smoking. However, there is moderate-certainty evidence that cutting down before quitting may result in similar quit rates to quitting all at once, which suggests that cutting down may be a helpful approach. We rated this evidence as moderate because there is a chance that future studies may find that cutting down helps slightly more or slightly fewer people to quit than when people quit all at once. There is also moderate-quality evidence that people may be more likely to quit by cutting down first when they use a stop-smoking medicine like varenicline or a type of fast-acting NRT to help them. We rated this evidence as moderate certainty because there were not enough people taking part; more studies are needed.
In this review, nine studies evaluating various non drug treatments to treat spasticity in adult with MS were included, comprising a total of 341 participants. Results from these studies suggest that all included non pharmacological therapies have low level of evidence or no evidence in improving spasticity in people with MS. However, caution should be used in the interpretation of the results, due to the poor methodological quality of all the included studies. More research is needed to determine the usefulness of these interventions before they can be recommended as routine treatments.
A systematic search up to the end of October 2016 identified eight studies that looked at four different types of immunotherapy in 4732 people. Studies were only included if patients were randomized to a form of immunotherapy included in this review or a standard form of targeted therapy. One study was funded by a public institution whereas all the others were supported by drug companies. The study participants were generally representative of people with advanced kidney cancer. The majority of people had their kidney cancer removed before starting treatment. We compared studies of people who had previously received standard medicine (821 participants) to those of people who had not (3911 participants). All studies reported our main outcome of interest; the chance of longer survival including the survival for one year. We also focused on the frequency of severe treatment side effects, quality of life and the delay in disease worsening. Interferon-α was the most commonly used therapy option prior to the era of targeted therapies. Two studies with 1166 participants compared interferon-α alone (monotherapy) to targeted standard therapy. Interferon-α is probably inferior to tested targeted therapies called sunitinib and temsirolimus. Patients with interferon-α monotherapy probably have a shorter time to worsening of cancer. They may have similar quality of life and a slightly more severe treatment side effects. Adding temsirolimus to interferon-α probably does not improve survival compared to temsirolimus alone, but may result in more major side effects (one study). Two studies compared interferon-α to a combination of interferon-α and bevacizumab in 1381 previously untreated participants. There was a slightly increased death rate with probably fewer major side effects for people treated with interferon-α alone. Two studies evaluated vaccines. Vaccines may lead to similar death rates and side effects in people with advanced kidney cancer. For patients who had already undergone systemic treatment, one study with nivolumab, a novel checkpoint inhibitor, improved average survival by more than five months when compared to the targeted standard therapy, everolimus. The effects are probably accompanied by better quality of life and fewer major side effects. We had reduced confidence in the results of the studies we analyzed (moderate- or low-quality evidence) because patients and treating physicians were often not blinded to the treatment and involved relatively few patients.
We included 16 trials encompassing 2933 colonoscopies in this review. The review showed that completeness of colonoscopy was similar between water infusion and standard air insufflation, and that adenoma detection (participants with at least one adenoma detected) was improved with water colonoscopy (36% versus 31% in the air group). In addition, participants experienced significantly less pain with water colonoscopy compared with the standard procedure. Detection of cancer and precancerous lesions during standard colonoscopy is far from perfect. Improvements in adenoma detection by water infusion colonoscopy, although small, may help to increase the rate of adenoma detection. This may reduce the risk of colorectal cancer development after a colonoscopy without abnormal findings.
This review looked at different tests used to identify blood vessel abnormalities in the brain. Intra-arterial digital subtraction angiography (IADSA) is the standard test used and involves positioning a tube, introduced through a blood vessel in the groin, into blood vessels near the brain. Dye is directly injected into the brain's blood vessels using this tube. Computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) are newer tests that may be done without any injections (MRA) or only through an injection into the arm (CTA and MRA). This review investigated the accuracy of CTA or MRA, or both, compared with IADSA after intracerebral haemorrhage. We found eight studies (involving 526 participants) that compared CTA with IADSA and three studies (involving 401 participants) that compared MRA with IADSA. Both CTA and MRA appear to have good accuracy when compared with IADSA. However, the studies were small and were limited in many cases by their design. Further research that looks at accuracy, practicality, and costs is needed.
We grouped the 28 included trials according to the kind of supplement they used and how it might work. Most of the trials were not originally designed to study cognition or dementia and used only simple measures of cognition. Very few studies investigated whether participants developed dementia. Long-term studies are probably needed to find effects on the risk of dementia or cognitive decline but only 10 studies had an average length of follow-up longer than five years. The studies were generally well-conducted although the longer trials had difficulty following up all of the participants and this could have biased some of the longer-term results. There were 14 trials of B vitamins (folic acid, vitamin B6, vitamin B12) with nearly 28,000 participants, mainly in their 60s and 70s. Most of these trials were quite short (less than two years). We found no evidence that B vitamins had any effect on cognition. There were 8 trials of antioxidant vitamins (beta-carotene/vitamin A, vitamin C, vitamin E) with approximately 47,000 participants. These trials tended to be longer than the B vitamin trials so may have had more chance of detecting effects on dementia and cognitive decline. The results were mixed. We found low-certainty evidence of better overall cognitive function after an average of 18 years taking beta-carotene and after five years to 10 years taking vitamin C, but no effects after shorter periods of treatment. There were also small benefits of beta-carotene, vitamin C, and antioxidant combinations on memory at some time points but not others. There was no evidence of any benefits from vitamin E alone. Two studies examined the risk of developing dementia. One found no effect of a combination of antioxidant vitamins and the other found no effect of vitamin E, either alone or combined with the mineral selenium. Most of the studies did not report any information about harmful effects. One included trial was designed to look for an effect on the risk of prostate cancer; it found a higher risk among the men taking vitamin E. There was a small trial of vitamin D supplements which found they probably had no effect on cognition over six months. There were longer trials of vitamin D with calcium (one trial), zinc and copper (one trial), and complex multivitamins (three trials). All lasted between five and 10 years, but none of them found any evidence of beneficial effects on cognition. One trial found no effect of selenium taken for approximately five years on the risk of developing dementia. We found no good evidence to suggest that middle-aged or older people can preserve cognitive function or prevent dementia by taking vitamin or mineral supplements. There were a few positive results associated with long-term use of antioxidant vitamins, particularly beta-carotene and vitamin C, although the effects were small. Further research into the effects of these vitamins may be worthwhile.
The evidence is current to May 2016. We identified six eligible primary prevention trials including 16,135 individuals without established cardiovascular disease that compared fibrate therapy with placebo or usual care. The mean age of the trial populations varied between 47.3 and 62.3 years; the majority of included individuals had diabetes mellitus type 2. The mean treatment duration and follow-up of participants across trials was 4.8 years. Moderate-quality evidence suggests a risk reduction of 16% with fibrate therapy for the combined outcome of death due to cardiovascular disease, heart attack, or stroke. In absolute terms, the risk for this combined outcome in patients with cardiovascular risk factors but without established cardiovascular disease was on average reduced from 5.0% to 4.3% over five years. Moderate-quality evidence also suggests a risk reduction for fatal and non-fatal heart attacks with fibrates, but there is low-quality evidence for no risk reduction for overall mortality or death from non-CVD with fibrates. Very-low quality evidence suggests that there is no increased risk for adverse effects with fibrate treatment. The reporting of adverse effects by identified trials was very limited. Data on quality of life were not available from any included study. Trials that evaluated fibrates in the background of statin treatment showed no benefits in preventing cardiovascular events.
. The review includes 10 small, short studies published mainly in the 1980s involving a total of 261 people. . One small study found that after 2 weeks' treatment both alpha-methyldopa and reserpine may lead to clinically important improvement in tardive dyskinesia symptoms compared with placebo, but the quality of evidence was low. We are uncertain about the effect of reserpine versus alpha-methyldopa; quality of evidence was very low. Another small trial compared tetrabenazine and haloperidol after 18 weeks' treatment, but again we are uncertain about the effect as the quality of evidence was very low. The included studies did not report on any harmful effects of the drugs. . Evidence is weak, limited, short term, and small scale. It is not possible to recommend these drugs as a treatment for tardive dyskinesia and their use is entirely experimental. There is a need for larger and more rigorous research in the area. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (mcpin.org/).
Cochrane researchers conducted a review of the effects of group therapy for people living with human immunodeficiency virus (HIV). After searching for relevant trials up to 14 March 2016, they included 16 trials reported in 19 articles that enrolled 2520 adults living with HIV. The included trials were conducted in the USA (12 trials), Canada (one trial), Switzerland (one trial), Uganda (one trial), and South Africa (one trial), and published between 1996 and 2016. Ten trials recruited men and women, four trials recruited homosexual men, and two trials recruited women only. What is group therapy and how might if benefit people with HIV? Group therapy aims to improve the well-being of individuals by delivering psychological therapy in a group format, which can encourage the development of peer support and social networks. Group therapy often also incorporates training in relaxation techniques and coping skills, and education on the illness and its management. Human immunodeficiency virus (HIV) causes a chronic, life threatening, and often stigmatising disease, which can impact on a person's well-being. Group therapy could help people living with HIV to adapt to knowing they have HIV, or recover from depression, anxiety, and stress. What the research says Group-based therapy based on cognitive behavioural therapy may have a small effect on measures of depression, and this effect may last for up to 15 months after participation in the group sessions (low certainty evidence). This effect was apparent in groups who did not appear to be depressed on clinical scoring systems before the therapy started. The research also showed there may be little or no effect on measures of anxiety, stress, and coping (low certainty evidence). Group-based interventions based on mindfulness have been studied in two small trials, and have not demonstrated effects on measures of depression, anxiety or stress (all very low certainty evidence). No mindfulness based interventions included in the studies had any valid measurements of coping. Overall, the review suggests that existing interventions have little to no effect in increasing psychological adjustment to living with HIV. More good quality studies are required to inform good practice and evidence.
Two eligible studies were included in the review. These studies vary significantly in interventions, methodology and reported outcomes. One study reported that removal of the inferior wall through the antrum and removal of the medial wall through the nose had similar effects in reducing exophthalmos but the latter had fewer complications. This study was disadvantaged by short-term follow-up and did not report on our primary outcome measure (success or failure of treatment). The second study suggested that intravenous corticosteroids achieve better visual recovery (56%) than surgical decompression (17%) as a first line treatment for optic neuropathy. It suggested that fewer secondary surgical procedures were required when treated with intravenous corticosteroids but their use related more frequently to side effects with short duration. This study was weakened by the small number of participants involved. Until more evidence is available we cannot recommend any particular intervention. This review has identified a need for more randomised controlled trials to provide further reliable evidence on the effective use of orbital decompression for thyroid ophthalmopathy. These trials should review the balanced two-wall, three-wall and orbital fat decompression techniques. These studies should address the reduction of exophthalmos, disease severity, complication rates, quality of life and cost of the intervention.
In this review, we investigated how well nalbuphine worked, compared to placebo and other opioids, in children with postoperative pain. We also looked at the side effects. We performed a systematic literature search in July 2013. Ten randomised controlled trials with 658 patients were included. The patients were children aged from 0 - 18 years and most did not have any other relevant medical conditions. The overall quality of evidence was low, so this review could not definitively show that nalbuphine is better than placebo. The same holds true for the comparison with other opioids (morphine, tramadol, pethidine, piritramid). We were not able to comment on side effects due to the small numbers of participants in the trials. Future studies need to address these issues, including more robust data for effectiveness and side effects.
We identified 28 research studies across Europe, Australia, North America and China. On average across the studies, the rate of new hepatitis C infections per year was 19.0 for every 100 people. Data from 11,070 people who inject drugs who were not infected with hepatitis C at the start of the study were combined in the analysis. Of the sample, 32% were female, 50% injected opioids, 51% injected daily, and 40% had been homeless. Our study was funded by the National Institute of Health Research's (NIHR) Public Health Research Programme, the Health Protection Research Unit in Evaluation of Interventions, and the European Commission Drug Prevention and Information Programme (DIPP), Treatment as Prevention in Europe: Model Projections. Current use of OST (defined as use at the time of survey or within the previous six months) may reduce risk of acquiring hepatitis C by 50%. We are uncertain whether high coverage NSP (defined as regular attendance at an NSP or all injections being covered by a new needle/syringe) reduces the risk of becoming infected with hepatitis C across all studies globally, but there was some evidence from studies in Europe that high NSP coverage may reduce the risk of hepatitis C infection by 76%. The combined use of high coverage NSP with OST may reduce risk of hepatitis C infection by 74%. Quality of evidence ranged from moderate to very low because none of the studies used the gold standard design of randomised controlled trials.
The evidence is current to 20 September 2018. We included a single randomised trial (a type of study in which participants are assigned to one of two or more treatment groups using a random method) with 113 people allocated to immunotherapy including isotretinoin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2, and ch14.18, a distinct type of anti-GD2 antibody also known as dinutuximab. Another 113 people were allocated to receive standard therapy including isotretinoin. The results on overall survival and event-free survival favoured the dinutuximab-containing immunotherapy group. Other outcomes including those on adverse events were not adequately reported; more research is needed before definitive conclusions can be made regarding these outcomes. We assessed the quality of the evidence as moderate.
Study characteristicsWe searched medical databases for studies in which neither participants nor researchers were told which treatment was given (randomised double-blind trials). The efficacy of the two therapies was considered in terms of occurrence of relapse and progression of disease.Key results and quality of evidenceUp to August 2016, we found six studies comprising 2904 participants (1704 treated with IFNs; 1200 with GA) that met our inclusion criteria requirements. We found that the two therapies seemed to have similar effects or only small differences in the occurrence of relapse or progression.The quality of evidence was moderate overall, although in terms of the safety profile the quality of evidence was low. The risk for incomplete outcome data was found to be high, as some studies present incomplete reporting of adverse events and numbers of participants who dropped out.It is worth noting that all studies but one were sponsored by the drug industry. Furthermore, all of the studies were short-term, with a treatment duration of three years for one study and two years for the other four, while one study was stopped early after one year.
We searched medical databases up to 19 May 2017. We included 19 studies with 1548 adults of both sexes. The participants had had operations on the abdomen (tummy), heart, blood vessels of the lungs, back, lower limbs or various surgeries. Two studies mentioned financial support from the pharmaceutical industry or from medical equipment manufacturers. We do not think that this had an effect on the results as high or low volumes may be administered with any machine. We did not find a difference in 0- to 30-day mortality (death within one month). We found that using a volume lower than 10 millilitres per kilogram of body weight reduced the risk of pneumonia (lung infection) and increased the chances that people would be able to get back to their normal respiratory status immediately after surgery. Low volumes should be used preferentially during surgery. For every 1000 people operated on, 84 would have pneumonia after the operation if high volumes were used during surgery. This number was reduced to 43 if low volumes were used instead. Likewise, the number of people needing additional non-invasive ventilatory support (through a mask applied to the face) would be reduced from 115 to 36 if volumes lower than 10 millilitres per kilogram of body weight were used during surgery and the need invasive ventilatory support (through a tube inserted in the person's windpipe) would be reduced from 39 to 13. Hospital length of stay may be slightly reduced (equivalent to almost one day). We identified no possible harmful effects of using low volumes. We judged the reliability of the evidence as moderate for pneumonia and reduced need for ventilatory support (non-invasive or invasive). Results on these three outcomes may be affected with additional data.
Our updated review included data from 75 studies of 7200 patients with moderate-to-severe pain after an operation. We found high quality evidence that IV paracetamol or IV propacetamol provided pain relief for four hours for about 36% of people versus 16% of those receiving placebo. Direct comparisons with other painkillers, such as morphine and anti-inflammatories, did not show large differences (if any) in effectiveness, although this may have been due to the small numbers of patients studied. Low quality evidence showed that IV paracetamol and IV propacetamol produced few side effects. However, patients receiving IV propacetamol complained of pain at the site their medication was infused at more often than those receiving placebo or IV paracetamol. Due to the amount of data already included in our review, we think it is unlikely that any new studies will change our conclusions. However, we found very few studies that included children, so this is an area that requires further investigation.
The small number of included trials provided evidence which appeared to favour the use of antiemetics over placebo to reduce the number of episodes of vomiting due to gastroenteritis in children. A single oral dose of ondansetron given to children with mild to moderate dehydration can control vomiting, avoid hospitalization and intravenous fluid administration which would otherwise be needed. There were no major side effects other than a few reports of increased frequency of diarrhea.
There is a lack of good quality evidence to support the choice of any particular antiepileptic drug for the treatment of seizures in adults with brain tumours. Our searches identified one small randomised trial directly comparing two different antiepileptic drugs (phenytoin and levetiracetam) for the treatment of seizures in adults with brain tumours. No significant difference was identified between the effectiveness of these two drugs. This small study was intended as a feasibility study for a larger trial that was not carried out. We also identified one ongoing study of levetiracetam versus pregabalin for the treatment of seizures in adults undergoing chemotherapy, radiotherapy,or both for primary brain tumours although no data from this study were available at the time of preparing this review. We identified a number of other small studies but we excluded them from the review as they were not randomised controlled trials. There is a clear need for larger randomised controlled trials to study the effectiveness of different antiepileptic drugs in the treatment of seizures in adults with brain tumours.
We included all trials that compared any surgical technique with no surgery or placebo surgery, and also trials comparing different surgical techniques with each other, including fusion and spinal implants. All the patients included in these studies were diagnosed with lumbar spinal stenosis and had symptoms in the leg or thigh that worsened by walking or standing and were generally relieved by a change in position, such as bending forward or sitting. The main measure we used to compare how well the different types of surgery worked was how much less pain people felt as they went about their daily lives. We also looked at whether their leg pain improved, how much blood they lost during surgery, how long the surgery took, how long they had to stay in hospital, how many patients had to have another operation for the problem and how much the treatment cost. Twenty-four randomised controlled trials were included with a total of 2352 people. We did not find trials that compared surgery with no treatment or placebo surgery, so all included trials compared different surgical techniques. The quality of the evidence from these studies varied from very low quality to high quality. This large variation was mainly due to different study protocols, surgical techniques and quality of reporting according to the 'Risk of bias' assessment. We found that patients who had decompression plus fusion fared no better than those who underwent decompression surgery alone. In fact, decompression plus fusion resulted in more blood loss during surgery than decompression alone. Although the spinal spacers were slightly better than decompression plus fusion in terms of improvements on daily activities, there were no differences when they were compared with decompression alone. Finally, we found no differences between different forms of decompression.
The efficacy of nimodipine, a calcium channel blocker, has been tested in randomized controlled trials for the treatment of dementia, particularly Alzheimer's disease and multi-infarct dementia, the commonest forms of dementia in older people. The rationale for its use is to restrict the influx of calcium ions into neurons, and, by vasodilatation, to improve blood flow to the brain. This review found evidence of some short-term benefit attributable to nimodipine, mainly in measures of cognitive function and global impression, but not in activities on daily living, for patients with degenerative and multi-infarct dementia, and mixed dementia. Nimodipine is well tolerated with a low rate of adverse effects similar to that associated with placebo.
We included studies with children (younger than 18 years of age) suffering from acute severe pain as a result of injury or medical illness. The target intervention was INF administered for pain relief compared with any other drug intervention for pain relief (e.g. intravenous morphine) or non-drug intervention (e.g. limb splinting, wound dressing) provided in the emergency setting. The evidence is current to January 2014. We identified three studies that included 313 children with acute severe pain resulting from broken bones of the upper and lower limbs. These trials compared INF versus morphine administered by a needle into a muscle (intramuscular morphine) or via a drip into a vein (intravenous morphine), as well as standard concentration INF versus high concentration INF. The collective study population in these trials consisted of children three to 15 years of age. Males accounted for approximately two-thirds of the overall study population. The review concluded that INF may be an effective analgesic for the treatment of children in acute moderate to severe pain, and its administration appears to cause minimal distress to children; however, the evidence is insufficient to permit judgement of the effects of INF compared with intramuscular or intravenous morphine. No serious adverse events (e.g. opiate toxicity, death) were reported. Limitations of this review include the following: Few studies (three) were eligible for inclusion; no study examined the use of INF in children younger than three years of age; no study included children with pain resulting from a "medical" cause (e.g. abdominal pain seen in appendicitis); and all eligible studies were conducted in Australia. Consequently, the findings may not be generalizable to other healthcare settings, to children younger than three years of age and to those with pain from a "medical" cause.
We searched for trials, July 2015 and April 2017, using the Cochrane Schizophrenia Group's register of trials. The review includes 13 poorly reported randomised trials investigating the effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed TD as a result of taking antipsychotics. The trials randomised a total of 478 participants who had been ill for a long time. Vitamin E may protect against tardive dyskinesia. However, there is no clear evidence that vitamin E improves this problematic and disfiguring condition. Available evidence is weak, limited and poor and we are unable to make any conclusions regarding the use of Vitamin E for antipsychotic-induced tardive dyskinesia. Well-designed trials involving a large number of participants investigating the effects of vitamin E over long periods of time are needed to determine whether this vitamin provides an effective treatment option for tardive dyskinesia. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (http://mcpin.org/).
We included seven studies on treadmill intervention on 175 children with Down syndrome, cerebral palsy, general developmental delay or children with moderate risk for delay. Studies used home-based or clinic-based treadmill protocols, ranging in duration from six weeks to several months, or until the children walked independently. Treadmill training versus no treadmill training was compared in five studies, including 117 children with one of the above mentioned risks. Treadmill training with or without orthotics (braces) was examined in 22 children with Down syndrome. High-intensity versus low-intensity treadmill training was compared in 36 children with Down syndrome. Compared to no treadmill intervention, treadmill training helped 30 children with Down syndrome to walk earlier, but did not help 28 infants at moderate risk for developmental delay. Overall, treadmill intervention did not improve overall gross motor function or gross motor skills related to standing. One study, which compared treadmill intervention with and without orthotics in 17 children with Down syndrome, suggested that adding orthotics might hinder gross motor progress. However, 20 ambulatory children with developmental delay, who engaged in treadmill training at preschool, improved walking skills. Twelve children with cerebral palsy, who received intensive treadmill training, showed faster achievement of motor milestones than children without treadmill training. None of the studies reported problems or injuries from the treadmill training. Overall, support for the intervention is limited. Confirmation from larger studies is necessary. Once efficacy of the intervention is established, optimal dosage research is needed. Statistical analysis was only performed on similar outcomes across studies. Standardized assessment for quality of evidence ranged from high to very low. Quality of evidence was determined by the number of children studied, completeness of the data, and random group assignment.
Review authors identified 20 studies that evaluated the effects of PCSK9 inhibitors in participants at high risk of CVD; studies were conducted in outpatient clinic settings. Review authors identified the studies included in this review through electronic literature searches conducted up to May 2016, and added three large trials published in March 2017. PCSK9 inhibitors constitute a class of drugs that decrease LDL-C and therefore may decrease the incidence of CVD. We examined the results of 20 studies, which showed beneficial effects on blood cholesterol concentrations of PCSK9 inhibitors at both six months and one year of follow-up. Although the magnitude of this beneficial effect differed between studies, all showed beneficial effects. In comparisons of PCSK9 inhibitors versus no PCSK9 inhibitors, current evidence suggests that PCSK9 inhibitors decrease CVD incidence without affecting the incidence of all-cause mortality. In comparisons of PCSK9 inhibitors versus alternative (more established) treatments such as statins or ezetimibe, high-quality evidence is lacking. Differences in risk between people treated with and without PCKS9 inhibitors suggest the absolute treatment benefit will likely be modest (e.g. < 1% change in risk). Most of the included randomised controlled trials (RCTs) were designed to explore biomarker associations; however, as all trials were industry funded, GRADE assessment revealed that the quality of the evidence was moderate. For associations with clinical endpoints (mortality and CVD), the quality of the evidence was moderate (placebo comparison) to very low (ezetimibe and statin comparisons).
The authors of this review wanted to evaluate the benefits and harms of vaccines for preventing anthrax. They identified four recent smaller randomized controlled trials of individuals and an older large cluster-randomized controlled trial with over 150,000 participants. The cluster trial provided limited evidence that a vaccine, based on a strain of live anthrax organisms incapable of causing disease, was effective in preventing cutaneous anthrax. More recent types of vaccines tested in the smaller trials, also based on inactivated components of the anthrax bacterium, appear to have few adverse events and to stimulate a good immune response. Several randomized controlled trials testing these newer vaccines are currently in progress. They will provide further information on the immunogenicity and safety of different vaccine regimens to be used for people at risk of anthrax exposure.
We searched scientific databases for studies of comparing the effects of physical exercise training within the first five years following the diagnosis of childhood cancer compared with no training. Participants were under 19 years of age with any type of childhood cancer. The evidence is current to November 2014. This review included five randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) and one clinical controlled trial (clinical studies where people are put into one of two or more treatment groups but this is not done in a random way) that evaluated the effects of a physical exercise training programme in children during cancer treatment. Childhood acute lymphoblastic leukaemia (ALL) is a cancer of the white blood cells and is the most common type of childhood cancer. For that reason, researchers often focus on this type of cancer since it will provide the largest number of patients in the shortest time-span. In total, our analysis included 171 participants with ALL. The results of the review showed that there were some small benefits of physical exercise training on body composition (percentage of fat mass, muscles, and bones), flexibility, cardiorespiratory fitness (how effective your heart and lungs are at delivering oxygen to your body), muscle strength and quality of life, but the evidence was limited. This can be related to an unsuitable programmes for children with cancer, or due to poorly designed studies. More studies assessing the effects of exercise are needed in a variety of childhood cancer populations. Furthermore, the current findings do not provide enough evidence to identify an optimal physical exercise training programme for children with cancer, neither do they provide information on the characteristics of people who will, or will not, benefit from such a programme. These important issues still need to be clarified.
This review aims to assess the effectiveness of pericyazine in the treatment of schizophrenia compared to older and newer antipsychotics.A search for studies was carried out in 2013 and five studies conducted between 1965 and 1980 were found and included in the review. The quality of evidence was rated by the authors to be very low, and their results were imprecise for many outcomes where they compared pericyazine and other older and newer antipsychotic drugs. The evidence is inadequate to determine whether pericyazine is better than other antipsychotics. The results of the analysis for the outcome of improvement were imprecise and the authors could not be certain that more people who took pericyazine were found to have not improved compared with those who took typical antipsychotics. More side effects, such as involuntary shaking, tremors, restlessness and spasms, were experienced by people who took pericyazine than other typical or atypical antipsychotics. These side effects are very unpleasant and the increased occurrence of them compared to other antipsychotics is an important finding considering pericyazine may not have additional benefits for the symptoms of schizophrenia. No studies reported outcomes on satisfaction of treatment or cost effectiveness, which require attention. This lack of evidence leaves people with schizophrenia, mental health professionals and policy makers with little information on the benefits, hazards or problems of pericyazine. Outcomes on the cost of care and satisfaction with treatment should be included in future trials which should also be larger, better conducted, and fully reported. (This plain language summary has been written by Ben Gray from Rethink Mental Illness).
Eleven studies evaluated interventions aiming to improve the management of osteoporosis by GPs. Five of these studies were sufficiently similar that we were able to combine their results. Our findings suggest that alerting the GP that a patient is at risk of osteoporosis and educating the patient, reminding them to visit their GP, leads to improved GP behaviour (diagnostic testing and medication prescribing). We determined that the quality or certainty of the evidence from these studies is high, so we are confident in these results. GP alerting on its own is also probably effective according to two studies and adding the patient-directed component probably does not lead to a greater effect. Of the ten studies on low back pain, seven showed that GP education and distribution of guidelines may lead to little or no improvement with regards to GPs' clinical behaviour. Two studies showed that providing GPs with guidelines and information on the total number of tests they request may have an effect on GP behaviour (resulting in a slight reduction in the number of tests). One study showed that using a combination of guidelines and GP reminders attached to test reports may result in a small but sustained reduction in the number of tests. Of the four studies on osteoarthritis, one found that GP behaviour may improve when prominent GPs are recruited to educate their colleagues. A second study showed slight improvements in patient outcomes (pain control) after training GPs on pain management. Of the three studies on shoulder pain, one study showed that there may be little or no improvement in patient outcomes (functional capacity) after GP education on shoulder pain and injection training. Of the two studies on other musculoskeletal conditions, one study on pain management showed worse patient outcomes (pain control) after GP training on the use of tools to measure pain. The 12 remaining studies across all musculoskeletal conditions showed little or no improvement in GP behaviour and patient outcomes. The majority of the studies did not investigate the potential adverse effects of the interventions and only three studies included a cost-effectiveness analysis. The direction of the targeted behaviour (i.e. increasing or decreasing a behaviour) does not seem to affect the effectiveness of an intervention. The certainty of the evidence was high from studies that examined the effectiveness of interventions to improve the management of osteoporosis by GPs, so we are confident in these findings. There were important limitations in how most of the remaining studies were conducted or reported, and we are less certain of the likely effects of these interventions to improve the management of musculoskeletal conditions.
In this systematic review we summarised and analysed the evidence from randomised controlled trials (RCTs) on efficacy and safety of methotrexate combined with additional chemotherapy in the treatment of adult, immunocompetent PCNSL patients regarding overall survival, progression-free survival, response rate, adverse events, treatment-related mortality and quality of life. We searched several important medical databases such as CENTRAL and MEDLINE and found one RCT with 79 patients that fulfilled our inclusion criteria. As a result, this review shows that patients treated with methotrexate plus cytarabine compared to high-dose methotrexate alone have a statistically significant improvement in progression-free survival and response rate. No statistically significant difference is shown for overall survival. Adverse events, especially infections, hepatotoxicity and haematological toxicities are more common in patients undergoing therapy with methotrexate plus cytarabine, although there are no differences in terms of treatment-related mortality. Owing to the small number of included trials and patients, the findings in this review remain uncertain and more RCTs with enlarged numbers of patients and longer follow-up periods are needed. However, the one analysed study demonstrated that RCTs are feasible on patients with this rare disease and should concentrate on overall survival.
In this systematic review, the efficacy of LED phototherapy was compared with conventional (non-LED) phototherapy. LED phototherapy was observed to be efficacious in bringing down the levels of serum total bilirubin, at rates similar to phototherapy with conventional light sources.
The authors identified twenty randomised controlled trials of sufficient quality involving 1150 women. These trials were carried out in both developed and developing countries. In general, local anaesthesia wound infiltration was of benefit in women having a caesarean section requiring regional anaesthetics because of a reduction in the use of opioid analgesia. Women undergoing general anaesthesia who had wound infiltration with local anaesthetics and peritoneal spraying required lower amounts of opioids in the first 24 hours post-operation compared to saline control. Those who had a general anaesthetic and the abdominal wall nerves blocked had reduced pain scores within the first 24 hours postoperative. Women who had regional anaesthesia and abdominal nerves blocked also benefited by decrease in opioid requirements. Non-steroidal anti-inflammatory drugs provided additional pain relief but with more side effects of pruritus. The commonly used local anaesthetic agents do have side effects but these are very rare, ranging from allergy to cardiovascular and central nervous system effects. There was no report of side effects in infants following local anaesthetic infiltration but the number of women studied was small. The longer theatre time and cost of the local anaesthetic may be offset by less use of postoperative analgesia. The effect on the development of chronic pelvic pain should be an important area of research.
The evidence is current to May 2016. We identified 16 clinical trials: 10 completed trials and six ongoing trials. We included the 10 completed trials in this review. Six trials included adults with acute myeloid leukaemia undergoing intensive chemotherapy, two trials included adults with lymphoma undergoing intensive chemotherapy and two trials included adults undergoing allogeneic stem cell transplantation. The age range of participants was between 16 and 81 years. Men and women were equally well represented. All trials took place in high-income countries. The manufacturer of the agent that was under investigation sponsored eight trials, and two trials did not report their source of funding. We identified nine trials (536 participants) assessing thrombopoietin mimetics and one trial (18 participants) assessing platelet-poor plasma. These trials were conducted between 1974 and 2015. No trial assessed artificial platelets, fibrinogen concentrate, recombinant activated factor VII or desmopressin). For adults treated with thrombopoietin mimetics, we are very uncertain whether there is a difference in the number of participants with: any bleeding, risk of life-threatening bleeding, number of platelet transfusions, overall risk of death or thromboembolic events because the quality of the evidence was very low. We found no trials of thrombopoietin mimetics that looked at: the number of days on which bleeding occurred, time from start of trial to first bleed or quality of life. For adults treated with platelet-poor plasma, we are very uncertain whether there is a difference in the number of participants with: any bleeding or risk of life-threatening bleeding. We found no trials that looked at: the number of days on which bleeding occurred, time from start of trial to first bleeding episode, number of platelet transfusions, overall risk of death, thromboembolic events or quality of life. The quality of the evidence was very low, making it difficult to draw conclusions or make recommendations regarding the usefulness and safety of thrombopoietin mimetics or platelet-poor plasma. There was no trial evidence for artificial platelets, fibrinogen concentrate, recombinant activated factor VII or desmopressin.
We included eight studies in this review (current until April 2017). The studies included a total of 3680 participants. Participants received either LMWH subcutaneously once daily, or no preventive treatment or placebo. New cases of DVT ranged from 4.3% to 40% in the control groups and ranged from 0% to 37% in the LMWH groups. The risk of DVT was lower in participants who received LMWH. Further analysis also showed a reduction in the occurrence of DVT when the use of LMWH was compared to no treatment or placebo in the following groups of participants: patients with below-knee casts, conservatively treated patients (patients not operated), operated patients, patients with fractures, patients with soft-tissue injuries, patients with above-knee thrombosis, and patients with below-knee thrombosis. No clear differences were found between the LMWH and control groups for pulmonary embolism. The studies showed less symptomatic venous thromboembolism in the LMWH groups compared with the control groups. No cases of death due to pulmonary embolism were reported. One study reported one death in the control group. There were few reported adverse effects in the treated patients. The main adverse events reported were cases of minor bleeding such as nose bleeds, blood in urine and dark stool. The use of LMWH in adult patients reduced DVT when immobilization of the lower limb was required, compared with no prevention or placebo. The quality of the evidence was downgraded to moderate due to risks of bias in some trials, such as lack of blinding of participants, or unclear reasons for excluding participants from the analyses. Low-quality evidence showed no clear differences in pulmonary embolism between LMWH and the control groups, but fewer symptomatic venous thromboemboli in the LMWH groups. The quality of evidence was downgraded due to methodological issues and imprecision of the results.
In May 2016 we searched for as many relevant studies as we could find that investigated the use of topical antibiotics on surgical wounds healing by primary intention. We managed to identify 14 studies which compared topical antibiotics with no treatment, or with antiseptics (i.e. other treatments applied to the skin to prevent bacterial infection), and with other topical antibiotics. Eight of these trials involved general surgery and six involved dermatological surgery (surgery involving only the skin). Many of the studies were small, and of low quality or at risk of bias. After examining them all, the authors concluded that the risk of having a surgical site infection was probably reduced by the use of topical antibiotics applied to wounds after surgery, whether the antibiotics were compared with an antiseptic, or to no treatment. As infection is a relatively rare event after surgery, the actual reduction in the rate of infection was 4.3% on average when the use of topical antibiotic was compared with antiseptic, and 2% when use of the topical antibiotic was compared with no treatment. It would require 24 patients on average to be treated with topical antibiotics instead of antiseptic, and 50 patients to be treated with topical antibiotic compared to no treatment in order to prevent one wound infection. Four studies reported on allergic contact dermatitis, but there was insufficient evidence to determine whether allergic contact dermatitis occurred any more frequently with topical antibiotics than with antiseptics or no treatment, and this should also be considered before deciding to use them. This plain language summary is up to date as of May 2016.
This review identified 13 studies (1403 participants) investigating interventions for either preventing persistent HSP-associated kidney disease or treating severe kidney disease. Five studies (856 enrolled children) which compared prednisone tablets given for 14 to 28 days with placebo tablets or no specific treatment for the prevention of persistent kidney disease at 6 to 12 months after onset of HSP. No significant reduction in the frequency of persistent kidney disease was demonstrated. Two studies (129 children) showed no benefit of aspirin and dipyridamole (antiplatelet agents) to prevent persistent kidney disease. One study (228 children) suggested that heparin given by injection could reduce the risk for persistent kidney disease but this treatment has the potential side effect of severe bleeding so its administration is not justified when only one third of children develop any kidney disease and in most this is not serious and resolves completely. There appeared to be no serious side effects in these studies but information provided on side effects was limited. In patients with serious kidney disease, two studies (one in adults and one in children) showed that cyclophosphamide was no more effective than placebo or supportive treatment in preventing progressive kidney injury. Two small studies comparing cyclosporin with methylprednisolone/prednisone (15 children) and mycophenolate mofetil with azathioprine (17 children) found no significant benefits of cyclosporin or mycophenolate. However the numbers of children studied were too small to completely exclude a benefit so further studies are required. No serious side effects were reported. There are few data from randomised controlled studies examining interventions used to prevent or treat serious kidney disease in HSP except for short-term prednisone to prevent kidney disease. There was no evidence of benefit of short courses of prednisone in preventing serious kidney disease in HSP.
We included four randomized trials with a total of 200 participants. The trials' duration ranged from single doses to 24 months of treatment. Three trials compared insulin (given via a syringe) to repaglinide tablets and recruited 180 people between them. Trial participants had an average age of 25 years and mild to severe diabetes. One of these trials (73 people) compared the two treatment groups directly over a two-year period; the remaining two trials each had a third treatment arm - one (seven people) compared single doses of insulin to repaglinide and to no treatment and the other (100 people) compared insulin to repaglinide and to a placebo (a dummy tablet with no active medication) for 12 months. The fourth trial recruited 20 participants with an average age of 34 years and compared the long-acting insulin glargine to short-term neutral protamine Hagedorn insulin over a 12-week period. We were not able to show that any of the treatments were better than the others. Only a few cases of hypoglycemia (low blood sugar) were seen in three out of the four trials (none in the longest trial), but these events resolved without further treatment. Longer-term studies are still needed to see how controlling cystic fibrosis-related diabetes affects lung function. There also needs to be research into the use of agents used together with insulin to enhance its action, especially those agents with additional anti-inflammatory potential. The participants would have been mostly able to tell which treatment they were receiving (e.g. insulin via a syringe or repaglinide as a tablet), so we thought there was a high risk from blinding in all trials (except when comparing repaglinide tablets to placebo (dummy) tablets). In two trials we are satisfied that participants were put into the different treatment groups completely at random; however, the other two trial reports were not clear on how it was decided which group the participants were put into. In only one trial was it clear that no one knew in advance which group a participant would be put into, in the other three trials there were no details given. There could be some bias if it was known in advance which group the next participant would be in, e.g. healthier participants might be put into one group to show better results for that treatment. There were also many results which were not fully reported in the publications. Finally, there may be bias in the results as the amounts of insulin and repaglinide given were not comparable.
The evidence is current to January 2015, the review includes three trials. Two assessed the effectiveness of vaccinating women of reproductive age (9823 infants): one (1182 newborns) assessed the effects of tetanus toxoid against polyvalent influenza in preventing tetanus and deaths within the 30th day of life; the other (8641 newborns) assessed the effects of tetanus-diphtheria toxoid against cholera toxoid administered in women of reproductive age in preventing newborn deaths. The third trial (48 women and their newborns) assessed the safety of tetanus toxoid diphtheria acellular pertussis vaccine (Tdap) administration during pregnancy in comparison with placebo. A protective effect against deaths caused by tetanus was observed among the newborns from mothers who received at least two doses of the tetanus toxoid vaccine when compared with newborns from mothers who were immunised with influenza vaccine. A similar protective effect was seen with at least two doses of the tetanus vaccine against newborn deaths. Cases of tetanus were less frequent among newborns from women who received at least one dose of tetanus toxoid. This evidence was of moderate quality. In the second trial immunisation of women of reproductive age with tetanus diphtheria toxoid had a greater protective effect against newborn deaths than did cholera vaccine. The quality of the evidence was low for this outcome. In the third study no serious adverse events (during pregnancy or in babies) were related to the receiving of Tdap vaccine. The women experienced more pain with the vaccine injection than with the placebo. The available evidence supports the implementation of immunisation programs for women of reproductive age or pregnant women in communities with similar, or higher, levels of risk of tetanus in newborn babies as at the two study sites.
We included six trials involving 418 patients for this review. The number of patients included in the trials varied from 30 to 131. Most of the trials were at high risk of systematic errors (ie, there was a potential to arrive at wrong conclusions because of the way the trial was conducted) and random errors (there was a potential to arrive at the wrong conclusions because of the play of chance). The comparisons performed included initial hepatic artery flush versus initial portal vein flush; blood venting via the inferior vena cava in addition to venting of storage fluid versus no blood venting; initial hepatic artery reperfusion versus initial portal vein reperfusion; simultaneous hepatic artery and portal vein reperfusion versus initial portal vein reperfusion; and retrograde inferior vena cava reperfusion versus simultaneous hepatic artery and portal vein reperfusion. There were no significant differences in the risk of death or graft loss, or in the major complication rates, between the compared groups in any of the comparisons. Quality of life was not reported in any of the trials. There were no significant differences in the transfusion requirements, intensive therapy unit stay, or hospital stay between the compared groups in any of the comparisons. We are unable to advocate or refute any technique of flushing and reperfusion in patients undergoing liver transplantation. Further well designed trials with low risk of systematic error and low risk of random errors are necessary.
Seven eligible studies were identified, all of which provided information on response to treatment (in 2061 patients), five on progression-free survival (in 1436 patients) and four on overall survival (in 1374 patients). The trials were generally old (conducted between late 1980s and early 1990s) and were of modest quality. Based on the data from these trials, 25.8% of the patients in the TOR group responded to the treatment, compared with 26.9% in the TAM group. The cancers of 50% of the patients in the TOR group had progressed after 6.1 months, compared with 5.8 months in the TAM group. Half of the patients in the TOR group survived longer than 27.8 months, compared with 27.6 months in the TAM group. The risk for progression and death in the TOR group was not significantly different from that in the TAM group. The frequencies of most adverse events were also similar in the two groups, except that the number of headaches occurring in the TOR group was only about one-seventh of that in the TAM group. However, considering the results of other large trials, we cannot exclude the possibility that this is purely a play of chance. Due to the lack of data, no conclusions can be made as to the long-term adverse effects achieved with either treatment. The evidence from this review suggests that TOR and TAM are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with advanced breast cancer. Thus, TOR may serve as a reasonable alternative to TAM when anti-oestrogens are applicable but TAM is not the preferred choice for some reason.
We identified two studies for inclusion. We found that giving steroids to babies affected with meningitis may reduce the number of children who would die or become deaf from the disease. However, most of this benefit was observed in only one trial. As of now, it appears as though steroids are not helpful with regard to preventing developmental delay. We are not able to make far reaching conclusions at this time, as the evidence that we found is limited and of low quality and could change if more results from larger and better designed studies become available.
There are no trials of the impact of tobacco advertising and promotional activities on people taking up smoking. However, there are studies following nonsmokers and their exposure to advertising (such as the number of tobacco advertisements in the magazines they read). The review found that in all these studies, nonsmoking adolescents who were more aware of or receptive to tobacco advertising were more likely to become smokers later.
We included six studies involving 559 children with pneumonia aged from 29 days to 12 years. This is an update of a review published in 2013 and includes three new studies. Studies were conducted in hospitals in Bangladesh, Brazil, China, Egypt, and South Africa. Pneumonia was described as moderate to severe in three studies, but severity was not described in three studies. All studies included children who received physiotherapy and others who did not. All children also received standard medical treatment for pneumonia. The studies assessed deaths, length of hospital stay, time taken to attain normal test results (no signs of pneumonia), and adverse events. Four studies reported sources of funding (a child health agency, university, government research grants), and two did not report study funding sources. One study reported fewer deaths in children who received bubble continuous positive airway pressure (bCPAP). Physiotherapy techniques (bCPAP, assisted autogenic drainage, and conventional chest physiotherapy) were not associated with shorter hospital stays. Two studies reported improvements in blood oxygen levels after chest physiotherapy (CPAP and conventional chest physiotherapy). No clear improvement in respiratory rate was observed after conventional chest physiotherapy. Based on the available evidence, we could not confirm if chest physiotherapy is beneficial or not for children with pneumonia. We assessed the overall quality of the evidence as low due to inadequate study methods and design, differing results among studies, and few data.
The evidence is current to July 2015. We found no new studies in this update of the review. This review identified three randomised controlled trials that compared giving platelet transfusions to prevent bleeding when the platelet count is 10 x 109/L (the current standard) or below versus giving platelet transfusions to prevent bleeding at higher platelet count levels (20 x 109/L or below or 30 x 109/L or below). None of the studies compared a lower trigger or alternative trigger to the current standard. These trials were conducted between 1991 and 2001 and included 499 participants. Two trials included adults with leukaemia who were receiving chemotherapy. One trial included children and adults receiving a stem cell transplant. Two of the three studies reported sources of funding. Neither of the studies that reported funding sources were industry sponsored. Giving platelet transfusions to people with low platelet counts due to blood cancers or their treatment to prevent bleeding when the platelet count was 10 x 109/L or below did not increase the risk of bleeding compared to giving a platelet transfusion at higher platelet counts (20 x 109/L or below or 30 x 109/L or below). Giving platelet transfusions to prevent bleeding only when the platelet count was 10 x 109/L or below resulted in a reduction in the number of platelets given. We found no evidence to demonstrate that giving a platelet transfusion when the platelet count was 10 x 109/L or below decreased the number of transfusion reactions compared to giving platelet transfusions at higher platelet counts (20 x 109/L or below or 30 x 109/L or below). None of the three studies reported any quality of life outcomes. Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue using platelet transfusions to prevent bleeding based on the current standard transfusion threshold (10 x 109/L). The evidence for most of the findings was of low quality. This was because participants and their doctors knew which study arm the participant had been allocated to, and also the estimate of the treatment effect was imprecise.
We searched for trials up to 24 March 2016 that compared removing CSF via lumbar or ventricular taps in all babies at risk of developing a build-up of fluid on the brain against a conservative approach where this was only done if there was evidence that the build-up of fluid was causing an excess of pressure in the brain. We included four trials that included a total of 280 preterm infants treated in neonatal intensive care units in the UK. The trials were published between 1980 and 1990. We found no evidence that removal of CSF by lumbar or ventricular taps reduces the need for a permanent shunt to be inserted. There was also no evidence that it reduced the risk of major disability, multiple disability, or death. There was insufficient evidence to determine if this approach can lead to an increased risk of developing an infection in the CSF. We assessed the outcomes of major disability, multiple disability, and disability or death as high quality evidence. We recorded the quality of the evidence for the outcomes of shunt insertion, and death or shunt insertion as low quality evidence, as there was an issue with the random allocation method in one included trial that reported on this outcome. For the outcomes of death and infection of CSF presurgery, the quality of the evidence was moderate due to the previously mentioned problem with allocation. In addition these studies did not have enough patients to sufficiently answer the question. In the case of the outcome infection of CSF presurgery, the results were inconsistent between the included trials.
The review authors identified three eligible controlled trials in which 569 patients were randomized to Lichtenstein or preperitoneal mesh repair. Due to methodological limitations in the included trials, the data were not pooled. Comparison of pain results in the individual trials showed that preperitoneal repair causes less chronic pain (relative risk (RR) 0.18, number needed to treat (NNT) 8; RR 0.51, NNT 5) compared to the Lichtenstein procedure in two trials involving 322 patients. One trial, including 247 patients, described more chronic pain after this repair (RR 1.17, NNT 77). The same trials favoured the preperitoneal technique concerning acute pain (RR 0.17, NNT 3; RR 0.78, NNT 7), whereas in the third trial it was almost omnipresent and thus comparable in both intervention arms (RR 0.997, NNT 333). This method also showed similar low recurrence rates after both types of repair. The results for other early complications were not consistent across the included trials. No mesh infections were reported. In conclusion, both techniques are valid causing few recurrences. Analysis of pain results in each trial shows some evidence that preperitoneal repair causes less or comparable acute and chronic pain compared to the Lichtenstein technique. As no robust conclusions concerning chronic pain after elective hernia surgery can be made, we highlight the need for homogeneous trials.
In this updated review we set out to estimate how well methadone worked, how many people had side effects, and how severe those side effects were – for example, whether they were so severe that participants stopped taking their methadone. In May 2016, we found just six studies with 388 adult participants. The studies were often small, and compared different preparations. For pain relief there did not seem to be much difference between methadone and morphine. For most people pain was reduced from moderate or severe to mild or no pain with methadone. Methadone is associated with some unwanted effects, mainly sleepiness, constipation, and dry mouth. These can be severe enough to stop people taking methadone. No data were available about the use of methadone in children. We would like to see more consistency in study design, and especially in study reporting, which should include information on unwanted effects and the outcome of pain reduced to tolerable levels, that is, no worse than mild pain, so that people with cancer are not bothered by pain. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low quality evidence means that we are very uncertain about the results. High quality evidence means that we are very confident in the results. The quality of the evidence was low or very low.
Our review brought together all available randomised controlled trials that compared the new techniques to surgery in the treatment of varicosities in the great saphenous vein. We found 13 trials, with a combined total of 3081 randomised patients, which met our inclusion criteria. Three trials compared foam sclerotherapy with surgery, eight trials compared endovenous laser therapy with surgery and five compared radiofrequency ablation with surgery (two studies had two or more comparisons with surgery). Overall the quality of the studies was acceptable, however none of the studies tried to conceal the treatment type from the participants, researchers and clinicians, or those who measured the outcomes. Most of the studies also had other biases. For foam compared with surgery, there was no difference between the treatment groups in the rate of recurrence as measured by a clinician and the rate of recurrence that was noted by patient symptoms. There was also no difference between the treatment groups for technical failure. Comparing laser therapy and surgery, there was no difference between the recurrence rates (either clinician noted or by symptoms) or for reopening of the treated vein (recanalisation). New vein growth (neovascularisation) and technical failure were both higher in the surgery group than in the laser group. For the comparison between radiofrequency ablation and surgery there were no differences between the treatment groups for recurrence, recanalisation, neovascularisation or technical failure. Outcomes that measure changes in patients' quality of life, operative complications and pain were not able to be compared directly, however quality of life generally increased similarly in all treatment groups and complications were generally low, especially major complications. Pain reporting varied greatly between the studies but in general pain was similar between the treatment groups. The limited evidence that is available supports that foam sclerotherapy, endovenous laser therapy and radiofrequency ablation are no worse than open surgery. However, it should be noted that there were large differences between the way the studies reported their outcomes, which included definitions and collection time points. These differences limited the findings of our review. We need more data from randomised controlled trials comparing these novel therapies to surgery before we really know their true potential.
This review identified two randomised controlled trials of 446 men with prostate cancer, with an average age of approximately 60 years, that compared LRP or RARP to ORP. We found no evidence as to how LRP or RARP compared to ORP in terms of reducing the risk of dying from prostate cancer, preventing the cancer from coming back or dying of any cause. Mens' quality of life was likely similar related to their urinary and sexual function. There appears to be no differences in postoperative surgical complications. LRP or RARP may have a small possibly unimportant effect on postoperative pain at one day and up to one week. However, no difference between RARP and ORP was found at 12 weeks postoperatively. Men having LRP or RARP likely have a shorter hospital stay and may need fewer blood transfusions. We found no trial evidence for any cancer outcome. The evidence for quality of life were moderate; that for overall and serious surgical complications were low quality. Postoperative pain were low (up to one week) and moderate (at 12 weeks) quality of evidence. The quality of evidence for hospital stay and blood transfusions were moderate and low, respectively. Collectively, the most outcomes were low to moderate quality of evidence. This means that our estimates are likely to be close to the truth but that there is a possibility that they may be different.
We included 51 studies with 9052 participants. Trials typically were four weeks long, and very few trials were longer. In all, 24 studies had some involvement of pharmaceutical companies such as funding or employment of the researchers. Particpants taking ketoconazole were 31% less likely than those given placebo to have symptoms that persisted at four weeks of follow-up. This was seen in eight studies with 2520 participants, but wide variation was noted between studies. Ketoconazole was as effective as steroids but had 44% fewer side effects. Without causing more side effects, ciclopirox was 21% more effective than placebo in achieving clinical clearance of rashes. Treatment effect on redness, itching or scaling symptoms of the skin was less clear. Evidence was insufficient to conclude that that one antifungal was superior to other antifungals, but this observation was based on few studies. Ketoconazole and ciclopirox are the most heavily investigated antifungals and are more effective than placebo. Other antifungals might have similar effects, but data are insufficient to underpin this. Common side effects were increased skin redness or itching, burning sensation and hair loss. No studies measured quality of life. Only one study reported on percentage of compliance in different treatment groups. Other studies used surrogates such as acceptability to represent compliance. We therefore could not assess the effect of compliance on treatment outcomes. One study on patients with HIV reported no clear effects of treatments. Evidence for the effects of ketoconazole compared with placebo or a steroid was assessed to be of low quality. Evidence derived from comparison of ciclopirox versus placebo was assessed to be of moderate quality. Better quality studies with longer follow-up and better reporting are needed to enlarge the evidence base for antifungals.
We identified three randomised studies up to August 2017, including 171 women over the age of 18 years, with moderate or severe CIN. The trials ran from June 2005 to April 2012, June 2002 to October 2003, and May to October 2004. One of them was discontinued before it was completed. The women were given either celecoxib or rofecoxib versus a placebo (sugar tablet) daily by mouth for a period of three to six months. With the addition of the third trial to this review, there is now a sufficient number of patients in the review to conclude that NSAIDs have minimal effect over placebo in causing regression of CIN. No patients progressed to invasive cervical cancer, and overall, the drug was well-tolerated compared to placebo. The studies appear to have been well-conducted. There are some questions related to the quality of evidence in relation to concealment and women dropping out of the study before completion of assigned medications. We therefore concluded that the certainty (quality) of the evidence was moderate. There was insufficient information to assess accuracy of the reporting of information. It is possible that there are other incomplete and unreported studies that have not been identified. The literature available at this time suggests that there are no convincing data to suggest NSAIDs as a treatment for CIN.
We found seven trials comparing LHRH agonist therapy (alone) to other treatments. There is not enough evidence to compare LHRH agonists directly to tamoxifen. Four of the trials compared an LHRH agonist to a now superseded chemotherapy regimen. For ER+ women, these trials showed no significant differences between LHRH agonists and chemotherapy on recurrence and death, but LHRH agonists had fewer side effects. Six trials compared LHRH agonists in combination with tamoxifen to other treatments. There is currently insufficient information to reliably compare this combination with tamoxifen alone. The LHRH agonist plus tamoxifen combination may reduce the risk of breast cancer recurrence, but not death, when compared to an LHRH agonist alone or chemotherapy alone. There is insufficient evidence to know whether an LHRH agonist plus an aromatase inhibitor is better or worse than an LHRH agonist plus tamoxifen. Three trials compared combining an LHRH agonist plus chemotherapy plus tamoxifen to chemotherapy alone. There was a reduction in the risk of breast cancer recurrence, and possibly death, with the combination treatment. It is important to note that the current standard of care for premenopausal women with ER+ breast cancer is five years of tamoxifen, often with chemotherapy. We found no trials of LHRH agonist-containing regimens versus this standard. The women in the trials in this review need to continue to be followed up so that the longer-term effects can be investigated, to 10 and more years after diagnosis. More research is also needed to help choose between different types of LHRH agonist, and to find out if the length of time that the drug is used makes a difference. It is also unknown whether there are important differences between the effects of LHRH agonists and ovarian ablation by surgery or radiotherapy.
Eight trials (1753 patients) met the criteria for inclusion in this review. The addition of chemotherapy to standard radiotherapy provides a small but significant benefit in patients with nasopharyngeal cancer, especially when chemotherapy is administered at the same time as radiotherapy. The role of chemotherapy given before or after the radiotherapy is more questionable.
Fourteen studies involving 29,319 people with at risk of diabetes complications were included and 11 studies involving 29,141 people were included in our analyses. Tighter blood glucose control generally didn't show any benefits for patients compared to less tight glucose control. There was no difference in the risks for patients on kidney failure, death, or heart disease complications. A very small number of patients (1 in every 1000 treated each year) might avoid a heart attack with more intense blood glucose management. Some patients would expect to have less protein leakage through kidney function although the clinical impact of this benefit is unclear in the long term. The potential problems with treatment, such as side effects and risks of very low blood glucose (hypoglycaemia) were not generally measured in the studies. The review concludes that people with diabetes receive uncertain benefits from tighter blood glucose control in the long-term and the immediate complications of this treatment approach are difficult to know accurately.
We identified seven trials involving 1558 participants where the aneurysm diameters of patients randomised to receive medical treatment were compared to those participants given a control medication or surveillance imaging alone. Four trials studied the effects of antibiotics on slowing aneurysm growth, and showed a small protective effect. Three trials studied the effects of beta-blockers, and demonstrated a very small protective effect. Notably, the beta-blocker drugs were associated with a large number of adverse effects. It was unclear whether either drug type delayed referral to aneurysm surgery. The accuracy of the results was limited by the low number of participants (especially important when trying to detect small changes in aneurysm growth rates) and some potentially damaging biases.
Two trials with a total of 2024 participants were included in this review. The trial published in 1983 in the USA included only adults, while the trial in 1998 in South Africa included only children. Both trials were set in large metropolitan cities. We were unable to combine the results of the two studies due to incomplete data. However, both trials came to the same conclusion regarding the use of chest X-rays in chest infections, except in the subgroup of patients with evidence of infection (infiltrates) on their X-rays. In both adults and children, chest X-rays did not result in significant differences in recovery time. In summary, there were no differences in patient outcomes between the groups with or without chest X-ray. Although both studies suggest that chest X-rays do not improve patient outcomes, it is not clear if this finding can be applied to all populations and settings. Results may be different in resource poor countries. Our conclusions are limited due to the lack of complete data available and by the risk of bias of the studies. Adverse effects of chest X-rays were not assessed by either study. We assessed the quality of the evidence from both trials as being moderate. For the remainder of this review, X-rays will be referred to as radiographs. The evidence is current as of February 2013.
We found and included five studies in our review. Three studies were conducted by the same group of researchers in Israel (Weiner 2000; Weiner 2002; Weiner 2002a), one study (Sampaio 2002) was conducted in Brazil and one trial was conduced in the United Kingdom (McConnell 1998). A total of 113 adults with asthma (46 male and 67 female) were included. No study included children. The studies showed a significant improvement in inspiratory muscle strength (PImax). People with asthma who received IMT on average increased their inspiratory muscle strength, but it was not possible to state whether this improvement seen in inspiratory muscle strength translated into any clinical benefit. Results from one study showed no significant difference between the training group and the control group (no treatment or usual care) for expiratory muscle strength, lung function, sensation of dyspnoea (breathlessness) and use of reliever medication. There were no studies describing exacerbation events that required use of reliever medication or emergency department visits, inspiratory muscle endurance, hospital admissions and days off work or school. Given the insufficient evidence found in this review, we believe that there is a need for more well conducted studies in order to assess the efficacy of IMT in people with asthma, including children. There were substantial differences between the studies, including the training protocol, duration of training sessions (10 to 30 minutes) and duration of the intervention (over 3 to 25 weeks). The methodological quality of the studies included in this update was difficult to accurately ascertain. Study samples were small and the risk of bias was mostly unclear, due to inadequate reporting. Overall the quality of the evidence included in the review was very low. This summary was current to November 2012.
Our review identified eight randomised controlled trials with 590 participants in total. Seven studies looked at the effects of hearing aids, four combination hearing aids and three sound generators. Seven studies allocated participants into parallel groups and in one study participants tried each intervention in a random order. The outcomes that we looked for were severity of tinnitus symptoms, depression, anxiety, quality of life and side effects. In general, the risk of bias in the studies was unclear. There was also little or no use of blinding. We did not find any data for our outcomes for any of our three main comparisons (comparing hearing aids, sound generators and combination devices with a waiting list control group, placebo or education/information only). There were also few data for our additional comparisons (comparing these devices with each other) and it was difficult to pool (combine) the data. One study compared patients fitted with sound generators with those fitted with hearing aids and found no difference between them in their effects on our primary outcome, tinnitus symptom severity, at 3, 6 or 12 months. The use of both types of device was associated with a clinically significant reduction in tinnitus symptom severity. Three studies compared combination hearing aids/sound generators with hearing aids alone and measured tinnitus symptom severity. When we combined the data for tinnitus symptom severity we found no difference between them. The use of both types of device was again associated with a clinically significant reduction in tinnitus symptom severity. Adverse effects were not assessed in any of the included studies. None of the studies measured depressive symptoms or depression, anxiety symptoms or generalised anxiety, or other important outcomes of interest in this review. Where outcomes that we were interested in for this review were reported, we assessed the quality of the evidence available as low. Using a hearing aid, sound generator or combination device might result in little or no difference in tinnitus symptom severity.
We searched for randomised controlled trials (RCTs) that compared any combination inhaler versus the same LABA component inhaler used by people with COPD. The studies were well-designed with low risk of bias for randomisation and blinding but there were high numbers of people who dropped out of the trials, which affected our confidence in the results for the outcomes. Overall, we found 14 trials involving 11,794 people with COPD. The results of the studies showed that combined inhalers reduced the frequency of exacerbations compared with their LABA component alone, from, for example, an average of one exacerbation per year on a long-acting beta2-agonist to an average of 0.76 exacerbations per year on a combined inhaler. The risk of mortality was similar between the treatments, although the overall result was not precise enough to rule out an effect in favour of either treatment. There was evidence of an overall increased risk of pneumonia with combined inhalers, from around three per 100 people per year on LABA to four per 100 per year on combined inhalers. There was no significant difference between treatments in terms of hospitalisations although the results of the three studies were inconsistent so we cannot be certain what this means. Combined treatment was more effective than LABA in improving health-related quality of life, symptoms such as breathlessness and cough, some measures of lung function, and also reduced rescue medication use, but it is difficult to tell whether these differences would be meaningful for individual people with COPD. Fluticasone/salmeterol led to more candidiasis and chest infections compared with salmeterol. Future research is required to show whether combined therapy reduces hospitalisations, and to better estimate the increased risks of pneumonia. This will need more trials with different doses of inhaled corticosteroids and including direct comparisons of different combination inhalers. The conclusions of the review are current to November 2011.
We reviewed studies retrievable as of July 2014. We included four prospective controlled studies of previously healthy children under 18 years of age who attended an ED of an urgent care clinic because of fever and respiratory symptoms. Based on these four studies, involving 759 study participants, we found that in previously healthy children coming to the ED with fever and respiratory symptoms, a rapid viral test showed a trend towards fewer antibiotic prescriptions, but this finding was not statistically significant. However, we found that rapid viral testing reduces the use of chest X-rays. There are also blood and urine investigations that can be undertaken. The true impact of this intervention on the frequency of blood and urine testing, as well as the length of the ED visit, requires trials with larger numbers of children. None of the included studies reported harm or adverse events related to the intervention tested. The quality of the evidence was considered moderate with regard to risk of bias, indirectness, imprecision, publication bias and inconsistency. While none of the studies used blinding, the impact of the use of rapid viral testing is in its ability to provide diagnostic information. Blinding of this interventions to the clinician would be impossible and make the intervention useless.
The evidence on which this review is based was current as of 20 May 2013. Seven studies with a total of 2241 participants all involving a direct comparison of ibuprofen to paracetamol or the combination of both were included in this review. All participants had surgery to remove a lower wisdom tooth or teeth that required bone removal or at least caused moderate to severe pain. Painkillers were taken after surgery and different doses of the drugs were compared. The majority of the studies took place in the USA with one in Puerto Rico. Four of the trials took place in clinical research facilities, two in university dental hospitals and one in a private oral surgery clinic. The age of participants differed slightly between studies but was broadly similar, ranging from 15 to 65 years old. All studies included male and female participants. All the studies included in this review looked only at pain relief and intensity information after a single dose of the painkiller after surgery. It is known that pain does continue after this and the drugs evaluated in this review are normally taken every six to eight hours (maximum of four times per day). Ibuprofen is more effective than paracetamol at all doses studied in this review. On limited evidence, the combination of ibuprofen and paracetamol appeared to be no more effective than the single drugs when measured two hours after surgery. However, again on limited evidence, it was found to be more effective than the drugs taken singly when measured at six hours after surgery. Participants taking the combined drug also had a smaller chance of requiring rescue medication. The information available regarding adverse events from the studies (including nausea, vomiting, headaches and dizziness) indicated that they were comparable between the treatment groups. However, review authors could not formally analyse the data as it was not possible to work out how many adverse events there were in total. All of the results (outcomes) comparing ibuprofen to paracetamol are of high quality. This means that further research is very unlikely to change our confidence in the estimates of the effect. When comparing combined versus single drugs, the body of evidence for the proportion of patients with > 50% maximum pain relief (TOTPAR) over two and six hours, was assessed as of moderate quality due to imprecise estimates based on single studies. This means that further research is likely to have an important impact on our confidence in the estimate of the effect. The body of evidence for the use of rescue medication was assessed as being of high quality.
The purpose of this review was to assess the available literature on the effectiveness and safety of pre-treatment surgical para-aortic lymph node assessment for locally advanced cervical cancer. We found only one randomised controlled trial (RCT) that assessed non-surgical staging versus surgical staging. We found limited evidence that suggested that clinical staging may offer a survival benefit (in terms of overall and progression-free survival) compared with surgical staging, but the strength of the evidence from this small trial is weak and the trial was at moderate risk of bias. There was no statistically significant difference in any of the reported outcomes between two surgical staging techniques examined in the trial. Due to the small number of women with locally advanced cervical cancer in only one included trial there was insufficient evidence to conclude that any of the staging techniques are superior to each other. This review highlights the need for future good-quality, well-designed trials that report not only survival and severe adverse event outcomes but also examine quality of life (QoL) outcome data.
Fourteen trials, including 3576 patients, were found that compared at least two different radiotherapy regimens. All involved patients with incurable lung cancer but the extent of the cancer and the fitness of the patients varied between the studies making direct comparisons difficult.The radiotherapy regimens in the trials varied from a single treatment to thirty treatments over six weeks.This update found no new trials and a meta-analysis (pooling the results of all trials) was carried out to see whether giving higher doses of radiation resulted in longer survival. All trials reported how long patients lived after their treatment and looked at the effect on symptoms as well as recording side-effects. However, the trials did not use the same methods for recording symptoms and side effects with some using the doctor's assessment and some using the patient's, making direct comparison difficult. This review shows that for most patients, a short course of radiotherapy with only one or two visits, improves common symptoms as effectively as longer courses, without more side effects. There is no strong evidence to support the view that a longer course of radiotherapy may give a better chance of living for one or two years, but it does result in more immediate side effects, especially sore swallowing. All the trials were randomised meaning patients involved in the study had an equal chance of getting either treatment. The use of a doctor's assessment of the patient's symptoms in some studies may have led to an under-estimation of the symptoms.
The two studies were very different; therefore we could not pool their data. One trial conducted internationally between 2002 and 2004, involving 515 women, found that cancer took longer to return in women receiving ACT (cisplatin and gemcitabine), and more women in the ACT group were alive after three years than in the standard treatment group (80% versus 69%). We considered the findings to be at high risk of bias in this trial, as women were given different drugs during standard treatment, and so the overall effect of the study treatment could not be attributed to the ACT alone. The other trial, which was conducted in several hospitals in Thailand between 1988 and 1994, involved 463 women. ACT (5-fluorouracil) did not improve the length of survival or the time taken for cancer to return in women in this trial. A trend towards increased side effects was reported in the ACT arms of both studies. We found insufficient evidence to support giving additional anticancer drugs to women who have received standard treatment for locally advanced cervical cancer, as currently only limited data are available from two very different trials.
The evidence is current to 30 January 2018. We included studies assessing the accuracy of stroke recognition scales when applied to adults suspected of stroke out of hospital. We included 23 studies evaluating the following scales: Cincinnati Prehospital Stroke Scale (CPSS; 11 studies), Recognition of Stroke in the Emergency Room (ROSIER; eight studies), Face Arm Speech Time (FAST; five studies), Los Angeles Prehospital Stroke Scale (LAPSS; five studies), Melbourne Ambulance Stroke Scale (MASS; three studies), Ontario Prehospital Stroke Screening Tool (OPSST; one study), Medic Prehospital Assessment for Code Stroke (MedPACS; one study) and PreHospital Ambulance Stroke Test (PreHAST; one study). Nine studies compared two or more scales in the same people. The results from five studies were combined to estimate the accuracy of ROSIER in the emergency room (ER) and five studies to estimate the accuracy of LAPSS when used by ambulance clinicians. Many of the studies were of poor or unclear quality and we could not be sure that their results were valid. Studies differed considerably in terms of included participants and other characteristics. As a consequence, studies evaluating the same scale reported variable results. We combined five studies evaluating ROSIER in the ER and obtained average sensitivity of 88% (88 out of 100 people with stroke/TIA will test positive on ROSIER). We were unable to obtain an estimate of specificity (how many people without stroke/TIA will test negative). We also combined the results for LAPSS, but the included studies were of poor quality and the results may not be valid. The rest of the scales were evaluated in a smaller number of studies or the results were too variable to be combined statistically. A small number of studies compared two or more scales when applied to the same participants. Such studies are more likely to produce valid results as the scales are used in the same circumstances. They reported that in the ER, ROSIER and FAST had similar accuracy, but ROSIER was evaluated in more studies. When used by ambulance staff, CPSS identified more people with stroke/TIA in all studies, but also more people without stroke/TIA tested positive. Current evidence suggests that CPSS should be used by ambulance clinicians in the field. Further research is needed to estimate the proportion of wrong results and whether alternatives scales, such as MASS and ROSIER, which might have comparable sensitivity but higher specificity, should be used instead to achieve better overall accuracy. In the ER, ROSIER should be the test of choice. In a group of 100 people of whom 62 have stroke/TIA, the test will miss on average seven people with stroke/TIA (ranging from three to 16). Because of the small number of studies evaluating the tests in a specific setting, poor quality, substantial differences in study characteristics and variability in results, these findings should be treated with caution and need further verification in better-designed studies.
In May 2016 we searched for clinical trials where gabapentin was used to treat pain due to fibromyalgia in adults. We found one study that met the requirements for this review. The study tested 1200 to 2400 mg/day of gabapentin compared with a placebo over 12 weeks, in 150 people. The study did not report the number of people with pain reduced by half at the end of week 12. At that time 5 in 10 people taking gabapentin and 3 in 10 taking the placebo had their pain reduced by at least one third. A report of feeling better to any degree was reported by 9 in 10 taking gabapentin and 5 in 10 taking placebo. About 2 in 10 people taking gabapentin stopped taking the medicine because of side effects, compared with 1 in 10 taking the placebo. The study did not report the number of people with serious side effects, but did report that there were no deaths. We rated the quality of the evidence as very low because there was only a single small study with important study limitations. Several factors reduced our confidence in the result. Very low quality evidence means that we are very uncertain about the results.
We searched for evidence up to September 2017 and found five randomised controlled trials (clinical trials where people are randomly assigned to one of two or more treatment groups) comparing MBSR to a variety of other interventions. We reported the effects of MBSR programmes compared with active controls (interventions in which participants received a similar amount of attention to those in the MBSR group, such as social support or progressive muscle relaxation) or inactive controls (interventions in which participants received less attention than those in the MBSR group, such as self help education). We were able to analyse study data from five randomised controlled trials involving a total of 201 carers. Findings from three studies (135 carers) showed that carers receiving MBSR may have a lower level of depressive symptoms at the end of treatment than those receiving an active control treatment. However, we found no clear evidence of any effect on depression when MBSR was compared with an inactive control treatment. Mindfulness-based stress reduction may also lead to a reduction in carers' anxiety symptoms at the end of treatment. Mindfulness-based stress reduction may slightly increase carers' feelings of burden. However, the results on anxiety and burden were very uncertain. We were unable to draw conclusions about carers' coping strategies and the risk of dropping out of treatment due to the very low quality of the evidence. None of the studies measured quality of life of carers or people with dementia, or the rate of admission of people with dementia to care homes or hospitals. Only one included study reported on adverse events, noting one minor adverse event (neck strain in one participant practising yoga at home) We considered the quality of the evidence to be low or very low, mainly because the studies were small and the way they were designed or conducted put them at risk of giving biased results. Consequently, we have limited confidence in the results. To summarise, the review provides preliminary evidence on the effect of MBSR in treating some stress-related problems of family carers of people with dementia. More good-quality studies are needed before we can confirm whether or not MBSR is beneficial for family carers of people with dementia.
Searches for high-quality randomised trials were carried out in 2008, 2013 and 2015. The review now includes 15 studies with 2428 participants. The studies randomised participants (in- and outpatients) with schizophrenia or schizophrenia-like illnesses into treatment groups that received oral risperidone or placebo. Results from limited data suggest that risperidone is more effective than placebo for reducing the overall symptoms of schizophrenia, and participants receiving risperidone were more likely to comply with treatment. However, like the older typical antipsychotics, risperidone was also associated with serious side effects, such as parkinsonism. The evidence available was very low quality. Information and data were limited, poorly reported, and probably biased in favour of risperidone . Nearly half of the included trials were funded by drug companies. Firm conclusions are difficult to make based on the results of this review. Better conduct and reporting of trials could increase confidence in the results. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/
Nineteen studies involving 10,400 people were included in this review. The studies lasted between 4 and 156 weeks. All of the people included in the studies had COPD of different severity. Both men and women were included, and most of the studies included only adults aged 45 or older. All studies compared a combined inhaler with a placebo that was identical in appearance to the combined inhaler, so the people in the trials did not know whether they were taking the drug or the dummy inhaler. Some of the studies included two groups treated with the combined inhaler; one group was getting a higher dose and one group was getting a lower dose. The evidence presented here is current to June 2013. Most of the studies were sponsored by the pharmaceutical industry. We found that people receiving a combined inhaler were less likely to have a flare-up (‘exacerbation’) of their COPD. The chance of having an exacerbation was reduced by about one quarter. A small reduction in the risk of death was seen over three years, although most of the evidence about death comes from one large, long trial called TORCH. According to TORCH, approximately 42 people would need to be treated with a combined inhaler for three years to prevent one death. We also found that people receiving combined inhalers had small improvements in quality of life, symptoms related to COPD and their breathing tests. However, these improvements may not have been very noticeable to them. People treated with combined inhalers were more likely to have a lung infection called pneumonia. Again, most of the evidence about pneumonia comes from the TORCH trial. According to TORCH, when compared with placebo, for approximately every 17 people treated with combined inhaler, one extra person would get pneumonia. People treated with combined inhalers were no more or less likely to experience serious unwanted events, including side effects, during treatment. No consistent differences were found between the three different types of inhalers included in this review. However, it is important to note that we cannot tell from this review whether it is the combination that is important or whether one of the two drugs in the combined inhaler may have had the real impact. The evidence presented in this review is generally considered to be of moderate quality. Most of the studies did not clearly explain how they decided which people would receive the combined inhaler and which would receive placebo, and this is an important part of a well-conducted study. Also, more people receiving placebo dropped out of the trials than those receiving a combined inhaler. This often happened because of exacerbations of COPD. This means that by the end of the trial, the groups might have been unbalanced, and this could affect the accuracy of the results.
The objective of this review was to evaluate the short-term efficacy of auranofin for the treatment of rheumatoid arthritis when compared to placebo. Our results show that auranofin appears to be efficacious in the short-term treatment of patients with RA (6 months), and has a small but clinically and statistically significant benefit on the disease activity of these patients. Its effects on overall health status and radiological progression are not clear at this time, but would appear to be modest. Auranofin may be most appropriate for those patients with early and mild disease who are more likely to respond to less potent (and less toxic) therapies.
The review authors searched the literature and were able to combine data from 11 randomized controlled clinical trials (3716 participants) comparing different durations of treatment with VKA in patients with a symptomatic VTE. Participants receiving prolonged treatment had around five times lower risk of recurrence of VTE. On the other hand, they had about three times higher risk of bleeding complications. Prolonged treatment did not reduce the risk of death. Prolonged use of VKA strongly reduced the risk of recurrent clots as long as they were used, but benefit decreased over time and the risk of major bleeding remained.
This review highlights that retinopathy of prematurity is a painful examination and that instillation of local anaesthetic eyedrops immediately prior to examination of the eye is associated with a reduction in pain scores, as assessed by validated pain scores. Ongoing research is required to determine the optimum local anaesthetic eyedrop and other potentially important methods of reducing pain, including swaddling, and sucrose.
This review aimed to compare surgical decompression with non-surgical treatments such as splinting or corticosteroid injections. Four trials were found and included, while three are awaiting assessment. The results suggest that surgical treatment is probably better than splinting but it is unclear whether it is better than steroid injection. Further research is needed for those with mild symptoms.
We found four studies that included a total of 2199 teachers. They evaluated three types of work changes. One intervention consisted of changes in teachers' tasks such as redesigning work, establishing flexible work schedules and redesigning the work environment. Another intervention consisted of a school-wide coaching support network alongside individual training for teachers, in order to deliver a child development programme. The third intervention consisted of several components: performance bonus pay, job promotion opportunities and mentoring. Changes in tasks of teachers In one study with 961 teachers in eight schools, changes in tasks of teachers combined with stress management training resulted in a small reduction in work stress levels after one year follow-up compared to no intervention. There was also a small increase in work ability, meaning how well a worker is able to perform his or her work. However, the authors did not report how they changed teachers' tasks, limiting the results' usefulness elsewhere. Changing organisational features There were two studies of school-wide coaching support combined with teacher training. In one study with 43 schools and 59 participating teachers, there was no considerable effect on anxiety or depression after two years follow-up compared to no intervention. In the other study with 18 schools and 77 participating teachers, there was no considerable effect on burnout or emotional ability after six months follow-up compared to no intervention. Burnout is a state of prolonged severe stress. Emotional ability means understanding other people’s emotions, and understanding and controlling ones own emotions. Both studies had a small number of participants. Multicomponent programme In one study with 34 schools and 1102 teachers, the intervention included performance bonus pay, job promotion opportunities and mentoring. After three years follow-up and compared to 300 similar schools, there was a moderate reduction in resignation of teachers in the intervention schools. However, authors reported results only for eight schools. The quality of the evidence was low for all interventions because the authors did not report all the results and lost many participants for follow-up. All included studies also had interventions directed at individual teachers combined with changes at schools. Therefore, new and better quality studies directed at schools will probably change the conclusions of this review. Changing the way teachers' work is organised at schools may improve the teachers' wellbeing and may reduce teacher resignations. We need better-designed research in the development and testing of work changes in schools. In future studies, whether work at schools is changed or not should be determined according to chance. These studies should also have several hundred participants.
We included 25 studies of which 4 studies are awaiting assessment. The 21 studies that could be analysed included a total of 3479 employees. Sixteen studies trained supervisor-employee interaction, either off-the-job (9 studies) or on-the job (7 studies). Five studies trained the design of working environments, off-the-job in 2 studies and on-the job in 3 studies. The 21 studies compared 23 interventions with no training, sham training or other training at various times of follow-up. There is no considerable effect of supervisor training on employees' stress (6 studies) or absenteeism (1 study) when compared to no training. There is inconsistent evidence that supervisor training may (2 studies) or may not (7 studies) improve employees' well-being when compared to no training. Data were missing from two studies, so we could not calculate the effects of training on employee well-being. There is no effect of supervisor training on employees' stress (2 studies) or absenteeism (1 study) when compared to a placebo training. Data were missing from one study, so we could not calculate the effects of training on employee well-being. One study that evaluated supervisor training compared to another type of training to reduce employees' stress did not provide enough data to calculate its effects. The quality of the evidence was very low for most outcomes due to risk of bias in the studies, inconsistent results, and imprecise effects. Researchers should consider the shortcomings of studies included in this review in order to conduct well-designed studies in the future and report them appropriately. Overall, the data suggest that training of supervisors may not lead to reduced levels of stress and absenteeism, or improved levels of well-being in their employees. The discrepancy between the apparent scientific consensus and the empirical evidence might be attributed to weak study designs.High quality studies are needed to clarify if supervisor training affects employees' stress, absenteeism, and well-being.
Different Chinese herbal medicine formulae (Shou Tai Pill, Yangxi Zaitai Decoction, Bushen Antai Decoction and some modified formulae) were used in the trials. The basic formula mostly contained some common Chinese herbal medicines (Chinese Dodder Seed, Chinese Taxillus Twig, Himalayan Teasel Root, Largehead Atractylodes Rhizome, Donkey-hide Glue, Eucommia Bark, Tangerine Peel, Szechwon Tangshen Root, White Paeony Root, Baical Skullcap Root, Mongolian Milkvetch Root, Chinese Angelica, etc). Western pharmaceutical medicines included tocolytic drugs such as salbutamol and magnesium sulphate, hormonal supplementation with human chorionic gonadotrophin, progesterone or dydrogesterone, and supportive supplements such as vitamin E, vitamin K and folic acid. We searched for evidence on 1 June 2015 and found nine trials (861 women) to assess the effectiveness of the interventions. All trials were methodologically poor and at an unclear risk of bias overall. No trial used placebo, no treatment or bed rest as a control intervention. One trial studied the effectiveness of psychotherapy compared with Chinese herbs. When Chinese herbal medicines were given in combination with other pharmaceuticals they were associated with higher rates of continuous pregnancy beyond 20 weeks (92.1% versus 72.0%, from two trials, involving 189 women) and live births (79.7% versus 44.2% from six trials, involving 601 women) compared to the other pharmaceuticals alone. Live birth rate was not different when comparing Chinese herbal medicines alone and other pharmaceuticals alone (in one trial, involving 80 women). A comparison of continuing pregnancy rate was not available in this trial. Compared with psychotherapy alone, the live birth rate was higher in the group of women who received a combination of Chinese herbal medicine and psychotherapy (91.1% versus 68.9%). The majority of studies did not report any information about adverse effects for the mothers or the babies. Only two trials (involving 341 women) reported that no maternal adverse effects were found (one trial comparing (combined) medicines with other pharmaceuticals and one trial comparing combined Chinese herbal medicine alone versus other pharmaceuticals alone). Only one trial (comparing Chinese herbal medicine alone versus other pharmaceuticals alone) reported that there were no abnormal babies either before or after delivery. No study recorded its limitations in the trial report. It is unclear which Chinese herbal medicines or their combinations are effective. According to the unique diagnosis and classification of Chinese medicine, the preparations (formulae) may differ according to the subtype of recurrent miscarriage. Most Chinese medicine practitioners modify the classical prescriptions depending on the individual clinical presentations. Some herbal medicines were modified from the classical formula for treatment. Therefore, the conclusion on effectiveness in our study could only represent the overall effects of Chinese herbal medicines on recurrent miscarriage in general. In conclusion, combined Chinese herbal medicines and other pharmaceuticals appear more beneficial than other pharmaceuticals alone for unexplained recurrent miscarriage, but the evidence on the effectiveness and safety of Chinese herbal medicines alone as treatment is unclear. We found no data to evaluate the safety and toxicity of this intervention for women and their babies and no data for all of our other maternal and infant outcomes. More high-quality studies are necessary to fully evaluate the utility of Chinese herbal medicines for unexplained recurrent miscarriage.
The review found one small RCT (26 patients) comparing human albumin plus the diuretic furosemide with placebo suitable for inclusion. We found nine studies on people with nephrotic syndrome that tested these comparisons but these were 'cross-over' studies which we judged not suitable. To find out whether there was any improvement after albumin, the study measured weight loss and serum sodium. The adverse effect measured was blood pressure. Although the authors reported increased weight loss we were not able to confirm this due to inconsistency between the data reported in the table and the text. There was no change in serum sodium or blood pressure. We judged these outcomes all to be of very low certainty. Death, quality of life, and kidney function were not reported. Because there was only one small study found we cannot tell whether albumin is effective in people with nephrotic syndrome and we do not know from the studies we looked at whether it is safe. There is no evidence in adults. We judged the evidence to be very low certainty. Therefore RCTs are needed.
There are a number of different iron-chelating agents, such as desferrioxamine (DFO) and deferiprone, and all were considered in the review of trials, although DFO has to be given intravenously and so will be of little use in most malarious areas. The drugs may also display adverse effects like headaches, dizziness, muscle pain, and tiredness. The review found seven trials of DFO and deferiprone involving 570 participants. Although the drugs may have helped in part with parasite levels, there seemed to be adverse effects including concerns about possibility of an increase in death. There is insufficient evidence to support the use of iron-chelating agents as adjuncts in the treatment of malaria, and further trials are not expected.
We included one trial with 117 children with SCD aged between six months and four years. This was a one-year doubIe-blind (both participants and doctors did not know which treatment group the participants were allocated to) controlled triaI comparing children taking folic acid supplements to those taking a placebo (a 'dummy' treatment). The trial investigators reported that folic acid supplementation led to higher levels of folic acid measured in the blood. However, there were no differences in haemoglobin concentrations at the end of one year. The trial also reported on clinical factors linked to treatment, including growth, major and minor infections, acute splenic sequestration, episodes of bone or abdominal pains. The investigators reported no differences in these outcomes from baseline to the end of the trial; however, the trial was not large enough to detect any possible differences reported between the folic acid group and the placebo group. In the included trial it was not clear how participants were allocated to receive folic acid or placebo. The method of making sure that participants and trial staff did not know what treatment each person was receiving (called allocation concealment) was also not described. These two factors mean that the trial had a high risk of biased results. The trial did not contain many participants. For many of its clinical endpoints, it was not designed to show differences between people taking folic acid and those taking a placebo. This means that the results from this trial are imprecise, and therefore hard to interpret. Finally, our review was meant to investigate folate supplementation (folate occurring naturally in foods, provided as fortified foods or additional supplements such as tablets) in children and adults. Because we only identified one trial that investigated one form of supplementation in children, the results are not useful for other populations. Therefore, we judged the evidence from the included trial to be of low quality. Based on just one low quality study with evidence only to show that folate supplementation raises the blood levels of folic acid, we cannot state whether this treatment is effective or not. More trials with more people and longer treatment duration (and follow-up) of folate supplementation in people with SCD are needed to strengthen this review; however, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.
This review aimed to assess the impact of infant massage on mental and physical outcomes for healthy mother-infant dyads in the first six months of life. A total of 34 randomised trials were included. Twenty of these had significant problems with their design and the way they were carried out. This means that the we are not as confident as we would otherwise be that the findings are valid. That is to say, the findings of these 20 included studies may over- or under-estimate the true effect of massage therapy. We combined the data for 14 outcomes measured physical health and 18 outcomes measured aspects of mental health or development. The results show limited statistically significant benefits for a number of aspects of physical health (for example, weight, length, head/arm/leg circumference, 24-hour sleep duration; time spent crying or fussing; blood bilirubin and number of episodes of illness) and mental health/development (for example, fine/gross motor skills personal and social behaviour and psychomotor development). However, all significant results were lost either at later follow-up points or when we removed the large number of studies regarded to be at high risk of bias. These findings do not currently support the use of infant massage with low-risk population groups of parents and infants. The results obtained from this review may be due to the poor quality of many of the included studies, the failure to address the mechanisms by which infant massage could have an impact on the outcomes being assessed, and the inclusion of inappropriate outcomes for population groups (such as weight gain). Future research should focus on the benefits of infant massage for higher-risk population groups (for example, socially deprived parent-infant dyads), the duration of massage programmes, and could address differences between babies being massaged by parents or healthcare professionals.
We looked at all the published scientific literature and identified four drug trials that evaluated different neuromodulators. Two small studies with a total of 52 patients tested the drug nefopam (which is only available in some parts of the world). One trial each tested capsaicin cream (31 participants) and a cannabis based mouth spray (58 participants). Note: use of medicinal cannabis is illegal and therefore unavailable in most countries. When patients took nefopam they had a greater improvement in pain levels, on average 21 points on a 100 point scale, than those patients who were given a placebo (an inactive substance that has no treatment value). However, patients on nefopam also developed side effects, which mainly consisted of nausea and sweating. Many patients stopped taking the drug because the symptoms were so bad. These studies were performed in the 1980s when treatment for RA was very different to what it is now. Until further, larger studies are carried out to better assess nefopam, with many other effective pain relieving medications on the market, the risks of harm seem to outweigh the benefit arguing against its routine use. In the one small study testing capsaicin cream (0.025%) in patients with persistent knee pain, patients also had better pain relief with capsaicin cream than for those given a placebo cream. On average, patients receiving the active treatment improved by 34 more points (out of 100) than the control group. The most common side effect was a local burning sensation at the site that the cream was applied. This was usually mild but was moderate to severe in a few patients. About 50% of patients who use capsaicin cream on their skin will develop this local burning but only 2 in 100 will stop treatment because of this. The one small study of the cannabis based mouth spray Setivax also showed reduced pain levels in patients, to a small extent. Pain was measured on a 0 to 5 point scale and there was an improvement in patients receiving Setivax of 0.74 points. About one in every three patients taking this medication developed a side effect, which was commonly dizziness (26%), dry mouth (13%) or light headedness (10%). Although this is only one study, weighing up these side effects and the minimal benefit on pain levels, until further trials are carried out we cannot recommend the use of this medication.
This review has merged studies from two previous reviews. One of the reviews was of competitions and incentives for quitting smoking. The studies that investigated incentives are now in a separate review. Here we include the studies which investigated competitions, alongside the studies originally included in our review of Quit & Win contests. We also searched for more recent relevant studies that were published up to June 2018. We include 20 studies of more than 11,000 participants that investigated competitions to encourage people to quit smoking. In five of these studies, groups of smokers recruited from workplaces competed directly against each other. In the other 15 studies, successful quitters were entered into prize draws. None of the studies in which groups of smokers competed against each other directly found that more people quit than in similar groups of smokers who were not entered into a competition. Combining the results of randomized controlled trials of lottery-type competitions, which provide the best evidence, did not show evidence that competitions increase rates of quitting smoking. Three Quit & Win contests did find that people who were in the contest had higher quit rates than people in a comparison community, who did not take part. However, these studies were of low quality and appeared to have very little effect on the overall smoking rates in the community, as fewer than one in 500 smokers appeared to quit because of the Quit & Win contest. Fourteen of the 20 studies included were randomized controlled trials, but many of these did not describe their methods well enough for us to decide whether they were of high quality. Overall, we judged the quality of the evidence included in this review to be very low, so we can draw no strong conclusions from the findings. It is important that any future research in this area is designed to be of high quality and is reported in detail, so that we can increase the confidence we have in our findings.
Two randomised studies are included in this review. Both studies targeted patients most likely to fall. One trial was of low height beds (22,036 patients) and the other investigated bed exit alarms (70 patients). The results of each study showed there is no significant increase or decrease in the rate of injuries or falls from bed. Although one study was large, fewer than half of the patients received a low height bed and so this group of patients may have been too small to detect a statistically significant benefit or harm in the analysis. No randomised controlled trials of bed rails were found. The researchers suggest that future reports should fully describe what standard care was received by the control group.
This review included 39 randomized and quasi-randomized controlled trials comparing abstinence-plus programs to various control groups (eg "usual care," no intervention). Although we conducted an extensive international search for trials, all included studies were conducted among youth in the US, Canada, and the Bahamas (total baseline enrolment=37724 participants). The included programs took place in schools, community centers, and healthcare facilities. We did not conduct a meta-analysis because of missing data and variation in program designs. Using various control groups, 24 of 39 evaluations showed a significantly protective intervention effect on at least one biological or behavioral outcome at short-term, medium-term, or long-term follow-up. Eight trials found no evidence that abstinence-plus programs affect self-reported sexually transmitted infection (STI) incidence and limited evidence that programs have a protective effect on self-reported pregnancy incidence. Results for behavioral outcomes were inconsistent across studies. Findings in almost every trial assessing HIV-related knowledge favored the intervention group over controls. No harms were observed for any outcome, including incidence and frequency of sexual activity. Limitations for this review include underreporting of relevant outcomes, reliance on program participants to report their behaviors accurately, and methodological weaknesses in the trials.
Four studies including 606 patients were included in this review. Pooled analysis of these trials revealed vedolizumab is significantly more effective than placebo (sham infusion) for inducing clinical remission and response (improvement of symptoms), as well as endoscopic remission (healing of inflamed mucosa in the colon) in patients with moderate to severely active ulcerative colitis. Evidence from one study suggests that vedolizumab is superior to placebo for preventing relapse (recurrence of active disease) in patients with ulcerative colitis in remission. Patients receiving vedolizumab were no more likely than placebo patients to experience side effects or serious side effects. Commonly reported side effects included: worsening ulcerative colitis, headache, nasopharyngitis (inflammation of nose and throat), upper respiratory tract infection, nausea, and abdominal pain. Further research is needed in order to define the optimal dose, frequency of drug administration and the long-term effectiveness and safety of vedolizumab used for induction and maintenance of remission in ulcerative colitis. Vedolizumab should be compared to other currently approved therapies of ulcerative colitis in these studies.
Cochrane researchers searched the available literature up to 4 March 2016 and included 37 studies. Most studies recruited participants from South Asia. Most participants were adults, with 22 studies including children. All of the RDTs evaluated detected Salmonella Typhi (typhoid fever) only. Quality of the evidence The Cochrane researchers evaluated the quality of the data for each study using a standardized checklist called QUADAS-2. High quality studies that compared different types of RDT in the same patients were few in number. Two-thirds of the included studies did not evaluate the RDTs in the context of patients who are typically tested for the disease. Many studies utilized a particular study design (a case control study) which risks overestimating RDT accuracy. In the studies evaluating the Typhidot RDT, it was often unclear how many test results were indeterminate, when the test cannot distinguish a current episode of infection from a previous disease episode. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low. Key results Sensitivity indicates the percentage of patients with a positive test result who are correctly diagnosed with disease. Specificity indicates the percentage of patients who are correctly identified as not having disease. TUBEX showed an average sensitivity of 78% and specificity of 87%. Typhidot studies, grouped together to include Typhidot, Typhidot-M, and TyphiRapid-Tr02, showed an average sensitivity of 84% and specificity of 79%. When Typhidot studies with clear reporting of indeterminate results are considered, the average sensitivity and specificity of Typhidot was 78% and 77% respectively. Test-It Typhoid and prototypes (KIT) showed an average sensitivity of 69% and specificity of 90%. Based on these results, in 1000 patients with fever where 30% (300 patients) have enteric fever, we would expect Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results to, on average, miss the diagnosis (give a false negative result) in 66 patients with enteric fever, TUBEX to miss 66, and Test-It Typhoid and prototypes (KIT) to miss 93. In the 700 people without enteric fever, the number of people incorrectly given a diagnosis of enteric fever (a false positive result) would be on average 161 with these Typhidot tests, 91 with TUBEX, and 70 with the Test-It Typhoid and prototypes (KIT). These differences in the number of false negative and false positive results in patients from the different tests are not statistically important. The RDTs evaluated are not sufficiently accurate to replace blood culture as a diagnostic test for enteric fever.
The purpose of this review was to evaluate the effectiveness of SSEs in reducing curve progression and postponing or avoiding invasive treatment such as surgery in adolescents with AIS. Two studies involving 154 patients total were included. The review found no evidences for or against SSE. The two included studies yielded very low quality evidence that SSEs added to other treatments are more effective than electrical stimulation, traction and posture training for avoiding curve progression, and that SSEs as a standalone treatment yield almost the same results as general physiotherapy. Possible limitations of this review included the small number of studies that met the inclusion criteria and a high risk of bias, particularly selection bias. More randomised controlled trials are needed in this area, along with a deeper understanding of the types of SSEs useful for the adolescent with AIS.
We looked for studies that compared strategies to support the implementation of health-promoting policies and practices in workplaces versus either no implementation strategy or different implementation strategies. Implementation strategies could include quality improvement initiatives, education, and training, among others. They could target policies or practices directly instituted in the workplace (e.g. workplace healthy catering policy), as well as workplace-led efforts to encourage the use of external health promotion services (e.g. employee gym membership subsidies). We found six eligible studies that investigated these strategies. Most took place in the USA, and workplaces were in the manufacturing, industrial and services-based sectors. The number of workplaces examined in the studies ranged from 12 to 114. Implementation strategies in the six studies targeted different workplace policies and practices: healthy catering; point-of-purchase nutrition labelling; environmental prompts and supports for healthy eating and physical activity; tobacco control policies; sponsorship of employee weight management programmes; and adherence to national guidelines for staff health promotion. All studies used multiple strategies to improve the implementation of these policies and practices, including: educational meetings, interventions tailored to the specific needs of the workplace, and workplace consensus processes to implement a policy or practice. Four studies compared implementation strategies versus no intervention, one study compared different implementation strategies, and one study compared two implementation strategies with each other and a control. Researchers used surveys, audits and observations in workplaces to evaluate the effect of the strategies on the implementation of workplace policies and practices. The evidence is current to 31 August 2017. When we combined findings from three studies, we did not find any difference in the level of implementation of health-promoting policies or practices between workplaces that received implementation strategy support versus those that did not, indicating that these strategies may make little to no difference. In the two trials comparing different implementation strategies, both reported improvements in implementation, favouring the more intensive implementation support group. Findings for effects on employee health behaviours were inconsistent and based on very low to low certainty evidence, so it is unclear whether the implementation strategies improved these outcomes. One of the included studies reported on cost, and none on the unintended adverse consequences of implementation strategies. There were few included studies, and they used inconsistent terminology to describe implementation strategies, limiting the strength of the evidence. We rated the certainty of the evidence as low for the effect of implementation strategies on policy and practice implementation, based on four randomised studies (where groups are randomly assigned to different study groups), and very low based on two non-randomised studies. We also graded evidence on employee health behaviours and cost outcomes as low and very low. The findings of the review do not provide clear evidence regarding the impact of implementation strategies on workplace health-promoting policy and practice implementation or on employee health behaviours. Further research is needed.
We identified nine trials including 973 people. We found that people were less likely to have bacteria in their urine after urodynamic studies if they had antibiotics (4% versus 12%). While they did have fewer urinary tract infections (20% compared with 28% with no antibiotics), this did not reach statistical significance. There were too few adverse effects, such as fever, pain when passing urine or a reaction to the antibiotics, for the findings to be reliable. However, people were less likely to have blood in their urine with antibiotics. There was no information about other treatments which might help reduce infections, nor about different doses or types of antibiotics.
We searched the scientific literature worldwide up to June 2016 for research studies of drug treatments for children with RAP. We found 16 studies that met our criteria, examining antidepressants, antibiotics, antihistamines, antispasmodics, a dopamine receptor antagonist, and a hormone treatment. Fourteen studies compared drug treatments to a placebo, and two to usual medical care. The trials were carried out in seven countries: seven in the USA, four in Iran, one in the UK, one in Switzerland, one in Turkey, one in Sri Lanka, and one in India. The studies included a total of 1024 children aged between five and 18 years. All children were recruited from outpatient clinics. Follow-up lasted between two weeks and four months. This review suggests there is no evidence for the use of medications to improve symptoms or the child's quality of life. Consequently, if medications are prescribed, this should be done within a well-conducted clinical trial. If a medication is prescribed to a child with RAP, it must be remembered that RAP varies with time, and therefore any improvement or worsening may due to the natural history of the condition rather than a medication response. Many of the studies had some weaknesses in their design and how they were reported, therefore the overall quality of the evidence for medications in RAP is low. The studies with better methods included few children and have not been reproduced by other researchers since.
The review looked to see if using CTG during pregnancy might improve outcomes for babies by identifying those with complications. It looked for studies that included women at both increased risk, and at low risk, of complications. The review included six studies with all of the women at increased risk of complications. Four of the studies were undertaken in the 1980s and two in the late 1990s. The included studies were not of high quality. There were no differences in outcomes identified (low/very low quality evidence), although when computerised interpretation of the CTG trace was used, the findings looked promising. However, CTG monitors, associated technologies and the way midwives and obstetricians care for women with different complications in pregnancy have changed over the years. This means that more studies are needed now to see if outcomes for babies at increased risk of complications can be improved with antenatal CTG, particularly computerised CTG.
Seventeen randomised controlled trials (3898 participants) were included in the review. One studied fibrin sealant, and the other 16 studied HA. Investigators compared embryo transfer in a medium containing high versus low or no hyaluronic acid and in a medium containing fibrin sealant versus transfer in a medium with no fibrin sealant. Outcomes reported included live birth rates, clinical pregnancy rates, implantation rates, multiple pregnancy rates and other adverse events. The mean age of the women ranged from 27.5 to 35.7 years. The evidence gathered is current to November 2013. Analysis of the 16 studies that were identified using functional concentrations of HA showed an increase in the chances of pregnancy and live birth (450 vs 367 per 1000) but also an increase in the chance of the more risky outcome of multiple pregnancy (282 vs 175 per 1000). This increase in multiple pregnancy rate may be the result of improved pregnancy outcomes due to the addition of the adherence compound and the policy of transferring more than one embryo back into the uterus. Evidence obtained for these comparisons was of moderate quality. It is important to note that evidence of a higher delivery rate was not found in all analyses; however, it was found in the overall meta-analysis. Based on the single identified study that used fibrin sealant, no evidence indicates that the addition of this compound to an embryo transfer medium improved pregnancy outcomes.
We searched medical databases for randomised controlled trials (where participants were randomly allocated to one of two or more treatment groups) of adults with MS. Neither patients nor researchers were told which treatment was given. Doctors had diagnosed MS and memory impairment using standard methods. Key results and quality of evidence Up to July 2013, we found only seven studies with 625 participants that met our requirements although the quality of the included studies was overall low. We did not find convincing evidence to support the use of these drugs as effective symptomatic treatments for memory disorder in people with MS. There was moderate-quality evidence that donepezil 10 mg daily was ineffective in improving memory in MS patients with mild memory problems, but it was well tolerated. Side effects such as nausea, diarrhoea and abnormal dreams, although not frequent, were reported for donepezil, while ginkgo biloba, memantine and rivastigmine were well tolerated and no serious side effects were reported. There is one ongoing study that may ultimately provide valuable evidence in the future updates.
We searched widely for clinical trials and found 14 trials of treatments for speech problems in hereditary ataxias. The trials involved 721 participants. The duration of treatment was between two weeks and two years. Thirteen trials compared a medicine to a placebo and the 14th compared a mixed physiotherapy and occupational therapy treatment to no treatment. Ten different medicines were tested: L-hydroxytryptophan (L-5HT) (two studies), thyrotropin-releasing hormone (TRH) (two studies), varenicline, riluzole, idebenone (two studies), betamethasone, coenzyme Q10 with vitamin E, buspirone, ɑ-tocopheryl quinone and erythropoietin. We did not find any studies of traditional speech therapies. There were three ongoing trials. When planning the review, we decided to use the percentage change in speech production after treatment as our primary measure of whether treatments were effective. None of the studies measured speech in a way that allowed us to report this. Five studies reported improvement in overall disease severity but only two studies, of riluzole in various ataxias and betamethasone in ataxia telangiectasia, demonstrated improvement of speech production. It is difficult to say whether these improvements in speech might make a meaningful difference to patients. A variety of minor adverse events occurred with the medicines, including effects on the stomach and intestines, such as feeling sick. This kind of effect caused two people taking L-5HT to stop treatment. Another person experienced this effect while taking idebenone. Two more people taking idebenone experienced heart or autoimmune problems; however, they each had experienced those problems earlier in their life. None of the other studies found differences in speech performance on active treatment. All trials had some problems in conduct or design that could potentially affect the findings. Most of the included studies were small and looked at a mixed group of people with different forms of ataxia. The current evidence base is of low or very low quality and does not allow us to decide whether treatments for speech problems in the hereditary ataxia syndromes are effective. The evidence is up to date to October 2013.
Although tranexamic acid did numerically reduce blood loss, there was no clinical benefit, as the difference in blood loss was minimal, and there was no difference in need for blood transfusion, suggesting that this level of blood loss did not make a difference to the patient's well-being. Additionally, there was incomplete and limited evidence regarding tranexamic acid-related adverse events, so we can say little about whether tranexamic acid is safe for women with advanced ovarian cancer. The evidence we found from a single study was therefore insufficient to support routinely giving prophylactic tranexamic acid for cytoreductive surgery. This review indicates the need for future good quality, well-designed randomised controlled trials to provide more evidence on the effectiveness, safety and appropriate administration of tranexamic acid. The quality of the evidence was variable; therefore the overall the strength of the evidence reported in this review is low, as it is based on only one small randomised controlled study.
This review was performed to find and assess all trials designed to answer whether lower blood pressure targets are better than standard blood pressure targets. Data from 7 trials in over 22,000 people were analysed. Using more drugs in the lower target groups did achieve modestly lower blood pressures. However, this strategy did not prolong survival or reduce stroke, heart attack, heart failure or kidney failure. More trials are needed, but at present there is no evidence to support aiming for a blood pressure target lower than 140/90 mmHg in any hypertensive patient.
We searched for randomised controlled trials on 30 June 2016 and 1 July 2016 and found 10 studies (23 reports) to include in our review. All the studies were of education and support for all mothers, not just those giving birth to more than one baby, which introduced methodological issues for looking specifically at multiple births. Trials recruited 5787 women (this included 512 women interviewed as part of a cluster randomised trial). The number of babies from multiple pregnancies was small and none of the studies had sufficient numbers to provide information about how interventions worked for mothers of multiples. There were several problems with how the studies had been done, including women knowing if they were in the group getting support. The authors of two of the studies sent us their findings for women with multiple births (42 women in total). The trials compared home nurse visits versus usual care (15 women), and telephone peer counselling versus usual care (27 women). They looked at the number of women stopping any or exclusive breastfeeding before four weeks after giving birth and before six months, without any clear improvements provided by the intervention. All 15 women in one study and 25 out of 27 women in the other had started breastfeeding. There was no information on breast milk expression. Other outcome measures were reported, including a measure of maternal satisfaction in one study of 15 women, but there were not sufficient numbers to allow us to draw any conclusions. No adverse events were reported. We could not draw conclusions from the evidence available from randomised controlled trials about whether education and support helps mothers of multiples to breastfeed. None of the studies were designed to offer tailored support or education to women who give birth to more than one baby. More research is needed to find out what types of education and support could help mothers of multiples to breastfeed their babies. Data from these studies should be presented and analysed in an appropriate way for multiple babies.
We included only studies that compared an exercise intervention with a usual care comparison or 'waiting list' control. Only studies that included sedentary people over the age of 18 with the same cancer diagnosis were eligible. Participants must have been allocated to exercise or usual care at random. We searched for evidence from research databases from 1946 to May 2018. We included 23 studies involving 1372 participants in total. Evidence suggests that exercise studies that incorporate an element of supervision can help cancer survivors. However, we still have a poor understanding of how to promote exercise long term (over six months). There is some concern that research is not being reported as clearly as it should be. We found that setting goals, graded physical activity tasks and providing instructions on how to perform the exercises could help people to do beneficial amounts of exercise. In addition, we found some evidence that in people who do meet recommended exercise levels, get fitter for up to six months. The main problems that we found regarding the quality of studies in this review included: not knowing how study investigators conducted randomisation for the trials and not knowing whether investigators who were doing trial assessments knew to which group the person they were assessing had been randomly assigned. The quality of the evidence from these studies was found to be low due to the majority of the trials often containing a low number of participants. The main conclusions from this review are that exercise is generally safe for cancer survivors. We have a better understanding of how to encourage cancer survivors to meet current exercise recommendations. However, there is still a lack of evidence of how to encourage exercise in cancer survivors over six months.
Our study assessed how effective these treatments are at enabling the sick-listed worker to return to partial or full-time work. We searched databases containing articles from different scientific journals and looked for studies that tested whether a certain type of treatment helped the worker to return to work when on sick leave because of an adjustment disorder. We found nine relevant studies. In total, 10 psychological treatments were evaluated and one combined treatment consisting of a psychological treatment and relaxation techniques. We found no studies on pharmacological interventions, exercise programmes or employee assistance programmes. The nine studies included in this review reported in total on 1546 participants. Of the 10 psychological treatments, five consisted of cognitive behavioural therapy and five of problem solving therapy, which are commonly used types of treatment for patients with mental health problems. Our results showed that workers on sick leave because of an adjustment disorder can be helped with making their first step back to work (i.e. partial return to work) by treating them with problem solving therapy. On average, workers who are offered problem solving therapy start 17 days earlier with partial return to work compared to workers who receive no treatment or the usual treatment from their occupational physician or general practitioner. However, we also found that cognitive behavioural therapy or problem solving therapy does not help the worker return to work with full-time hours any quicker than workers who receive no treatment or the usual treatment from their occupational physicians or general practitioners. These results are based on moderate-quality evidence, which implies that further research is likely to have an important impact on our confidence in the results and may change the results.
The review currently includes nine studies with around 60 participants per study. All of these studies are now over 60 years old, conducted between 1955 and 1962 and include people with the most severe illnesses. Key results  Chlorpromazine does better than reserpine for 'improvement in global state' with most trials reporting on this outcome. There was no clear difference between the drugs for 'occupational adjustment', 'general behaviour', and, rather surprisingly, adverse events and finally, leaving the study early. Quality of the evidence Judged by standards of today, the evidence is largely of limited quality. However, some of these 1950s studies are remarkable in their foresight and clarity.
We only found one study funded by Pfizer that met our inclusion criteria. A total of 64 participants with chronic pain due to chronic pancreatitis received either increasing doses of pregabalin (150 mg per day to 600 mg per day; 34 participants) or matching placebo (sham treatment; 30 participants) on an outpatient basis. The decision about whether a participant received pregabalin or placebo was made using methods similar to toss of a coin, to ensure that the participants in the two groups were similar. Participants received pregabalin or placebo for three weeks, then the outcomes were measured. Potential participants taking other pain-killers were allowed to take part in the study. Thus, this trial evaluates the role of pregabalin in addition to other analgesics for decreasing chronic abdominal pain due to chronic pancreatitis. Only the short-term outcomes were available in this trial. This trial found that the changes in opiate use (drugs similar to morphine), and pain scores from baseline were better in participants taking pregabalin compared to those taking placebo. It was not clear whether these changes had a significant impact on the life of the participants.This trial also found that there were more side-effects in participants taking pregabalin compared to those taking placebo. The differences between pregabalin and placebo were imprecise for short-term health-related quality of life, percentage of people with serious side-effects, and percentage of people requiring hospital admissions. Medium- and long-term outcomes, number of work days lost, and length of hospital stay were not available in this trial. The quality of evidence was low or moderate. As a result, further studies are required on this topic.
These three drugs, along with one other (pregabalin), are the subject of separate Cochrane reviews. For the present review, researchers in The Cochrane Collaboration reviewed the evidence about the effect of other antiepileptics in adult patients (≥ 16 years of age) with 'episodic' migraine (headache on < 15 days per month). They examined research published up to 15 January 2013 and found 10 studies of nine different antiepileptics. The majority of these drugs were no better than placebo for migraine prophylaxis (acetazolamide, carisbamate, clonazepam, lamotrigine, oxcarbazepine, and vigabatrin). In one study each, carbamazepine and levetiracetam were better than placebo, and there was no significant difference between zonisamide and topiramate (a drug proven to be effective for migraine prophylaxis). None of these studies was of high methodological quality. The quantity and quality of the evidence were such that no firm conclusions could be drawn about the effect or lack of effect of any of the antiepileptics studied.
We searched evidence from commonly used databases and it is current to 9 June 2016. We included five RCTs with 414 participants. These included studies comparing CHM to western medicine, CHM plus western medicine versus western medicine, and CHM plus surgery versus surgery. All the included studies were in Chinese. All studies had fewer than six menstrual cycles treatment duration and less than one year follow-up duration. None of the included studies reported live birth, all reported pregnancy, two reported ovulation and only one reported adverse events. There was insufficient evidence to support the use of CHM for women with PCOS and subfertility. No data were available on live birth, and there was no consistent evidence to indicate that CHM improves fertility outcomes. When CHM was compared with clomiphene (with or without laparoscopic ovarian drilling (LOD) in both arms), the pregnancy rates were no different between the groups. When CHM with follicle aspiration and ovulation induction was compared with follicle aspiration and ovulation induction alone, pregnancy rates were no different between the groups. When CHM with LOD was compared with LOD alone, the pregnancy rates were no different between the groups. However there was limited low quality evidence to suggest that the addition of CHM to clomiphene may improve pregnancy rates. There was no evidence of a difference between any of the comparison groups for any other outcomes. There was insufficient evidence on adverse effects to indicate whether CHM is safe. The quality of the evidence was low or very low. The main limitations in the evidence were failure to report live birth or adverse events, failure to describe study methods in adequate detail, and imprecision, with very low event rates and wide confidence intervals.
We identified five clinical trials that involved 3405 children, mostly from the same research group. Four trials were conducted in Finland and enrolled healthy children (three trials) or children with an acute respiratory infection (one trial). The fifth trial was conducted in the USA and enrolled otitis-prone children who were recruited from attendance at general medical practices. All five trials received governmental funding; and the Finnish study investigators have a US patent for the use of xylitol to treat respiratory infections. Xylitol, administered in chewing gum, lozenges or syrup, can reduce the occurrence of AOM among healthy children with no acute upper respiratory infection from 30% to 22%. There is no difference in side effects (namely, abdominal discomfort and rash). Based on these results we would expect that out of 1000 children up to 12 years of age, 299 would experience an AOM compared with between 194 and 263 children who would experience an AOM if they are provided with xylitol chewing gum. The preventive effect among healthy children with respiratory infection or among otitis-prone children is inconclusive. The quality of evidence was moderate for healthy children and children with respiratory infections but low for otitis-prone children.
We searched for evidence from high quality trials on environmental or behavioural interventions in older adults, living in the community or in residential settings, with irreversible vision impairment which aimed to reduce activity restriction or increase general physical activity. We found no trials that met the inclusion criteria for the review. Further research into this highly important issue needs to be done before any conclusions can be made.
The evidence is current to May 2017. We found three studies including 453 participants with MCI. Two studies evaluated the progression from MCI to ADD and one study evaluated the progression from MCI to any form of dementia. Regarding the two studies that evaluated the progression from MCI to ADD, one study had 401 participants with a follow-up of 1.6 years and the mean age was 72 years. The other study had 47 participants with a follow-up of three years, and the mean age was 72 years. The other study that looked at any form of dementia included 5 participants over 90 years old. Two of the studies were funded by the test manufacturer. The main limitation of this review was that our findings were based on only three studies, with insufficient detail on how the people were selected, whether the information from the scan was assessed separately from the final diagnosis. The studies were considered to be at high risk of bias due to potential conflicts of interest detected. In this review, we found the following results based on the three studies. At a follow-up of 1.6 years, using visual assessment, the scan correctly classified 89% of the participants who progressed to ADD but only 58% of the participants who did not progress to ADD. This means that in a group of 100 people with MCI, 15% of whom will develop ADD, we would expect 13 of 15 people to have a positive result and the other 2 participants to be falsely negative. Also 49 people who will not develop ADD would have a negative result, but 36 people who will not develop ADD would have a positive result (false positives). In the study that followed up people for three years and used visual assessment, the scan correctly classified 67% of people who progressed to ADD and 71% who did not progress to ADD. This means that in a group of 100 people with MCI, 19 of whom will develop ADD, we would expect 13 people to have a positive result of the scan and 6 people to have a falsely negative result. In addition, 58 of 81 participants who will not progress to ADD would have a negative result, but 23 people who will not develop ADD would have a positive result (false positives). The small number of participants evaluated at three years lowered our confidence on these estimates of accuracy. Regarding progression to any form of dementia, the extremely small number of participants meant that we were unable to provide meaningful estimates of accuracy. We conclude that 18F-florbetapir PET scans cannot be recommended for routine use in clinical practice to predict the progression from MCI to ADD or any form of dementia based on the currently available data. More studies are needed to demonstrate its usefulness.
We searched for randomised controlled trials comparing the efficacy (mortality, blood loss, need for re-intervention, subjective assessment of efficacy, duration and dose of therapy) and the safety of any type of treatment given to people with congenital bleeding disorders during any type of surgery. We found four trials to be included in this review. Two trials evaluated 59 people with haemophilia A or B receiving antifibrinolytic drugs (agents that reduce the breakdown of clots) or placebo in addition to the initial standard treatment before dental extractions. The remaining two trials evaluated 53 people with haemophilia A or B and inhibitors (antibodies that act against the factor concentrate therapy) receiving an different clotting concentrate, recombinant activated factor VII, both during and after surgery. These two trials evaluated different treatment options: high-dose compared with low-dose and a single large (bolus) infusion compared with continuous infusion. The trials included in this review provide some information in two specific situations in people with congenital bleeding disorders undergoing surgery. However, on the whole, there is not enough evidence from trials to define the best treatments for the various types of disease and types of surgery. Further trials would be useful to improve our knowledge but are difficult to carry out and currently do not appear to be a clinical priority. Indeed, both major and minor surgery are safely performed in clinical practice in these individuals based on local experience and data from uncontrolled studies.
However, there have not been any systematic reviews evaluating the effectiveness of the TAP block in reducing pain after surgery. We have searched for research investigating the effectiveness of rectus sheath (a similar block to TAP) and TAP blocks in providing pain relief after abdominal surgery. We have included eight studies, with a total of 358 participants in this review, that show some limited evidence that TAP blocks improve pain relief after abdominal surgery. More research is indicated, comparing TAP blocks with other standard methods of pain relief such as, morphine medication, epidural analgesia and local anaesthetic injection into and around the surgical wound. There are many studies currently underway or awaiting publication which assess the effectiveness of the TAP block and compare it with other techniques. We intend to include these studies in an updated version of this review in the near future.
On 28 October 2015, we looked for clinical trials using sumatriptan plus naproxen to treat migraine headache in adults. People were given either a combination of sumatriptan and naproxen, sumatriptan only, naproxen only, or a placebo (dummy) treatment. They did not know which treatment they were taking, and nor did the health professionals looking after them. We found 13 studies, of which 12 (with about 9300 people) provided information on how well the combination treatment worked. The combination of sumatriptan plus naproxen was better than placebo for relieving acute migraine attacks in adults. When the starting headache intensity was mild, 5 in 10 (50%) of people treated with the combination were pain-free at two hours compared with about 2 in 10 (18%) with placebo. Almost 6 in 10 (58%) people with moderate or severe pain who were treated with the combination had pain reduced to mild or none at two hours, compared with 3 in 10 (27%) with placebo. The combination was also better than the same dose of either drug given alone in these people. Results were 5 in 10 (52%) people with sumatriptan alone or about 4 in 10 (44%) with naproxen alone. The combination was better than placebo or either drug alone for relief of other migraine symptoms (nausea, sensitivity to light or sound) and loss of ability to function normally. Adverse events of dizziness, tingling or burning of the skin, sleepiness (somnolence), nausea, indigestion (dyspepsia), dry mouth, and chest discomfort were more common with sumatriptan (alone or in combination) than with placebo or naproxen. They were generally of mild to moderate severity and rarely led to withdrawal from the studies. The studies were carried out to high standards and were generally large enough to give reliable results, so that most of the results for efficacy were of high quality. Results for adverse events were downgraded to moderate quality because there were fewer events.
In this review, we focused on third wave CBT approaches, a group of psychological therapies that target the process of thoughts (rather than their content, as in CBT) to help people become aware of their thoughts and accept them in a non-judgemental way. The aim of the review was to find out whether third wave CBT was more effective and acceptable than other psychological therapy approaches for people with acute depression. The review included three studies, involving a total of 144 people. The studies examined two different forms of third wave CBT, consisting of acceptance and commitment therapy (ACT) (two studies) and extended behavioural activation (BA) (one study). All three studies compared these third wave CBT approaches with CBT. The results suggested that third wave CBT and CBT approaches were equally effective in treating depression. However, the quality of evidence was very low because of the small number of studies of poor quality that we included in the review; therefore it is not possible to conclude whether third wave CBT approaches might be more effective and acceptable than other psychological therapies in the short term or over a longer period of time. Given the increasing popularity of third wave CBT approaches in clinical practice, further studies should be prioritised to establish whether third wave CBT approaches are more helpful than other psychological therapies in treating people with acute depression.
We included trials comparing people with hemophilia receiving any psychological intervention compared with other individuals receiving a different intervention or no intervention at all. We found seven trials with 362 people with hemophilia aged between 6 and 65 years of age. Trials compared either a DVD plus information booklet or computerised learning or auto-hypnosis (self-hypnosis) or relaxation techniques to no treatment and people were selected for one treatment or the other randomly. The trials lasted from one to six months. All treatments were safe, no major side effects were reported. Psycho-educational interventions in children and adolescents seemed to promote a sense of self-efficacy and better self-management skills, but the quality of the evidence suggests that more rigorous experimental design is required. One trial in adults did not show any effect. Self-hypnosis and relaxation techniques were not tested for the primary outcome but were useful in decreasing the number and severity of joint bleeds when drug treatment was not available. The effects of these interventions on quality of life vary. The major problem we encountered in this review is the difference in trial designs, interventions and outcome measures used across the trials. We strongly suggest that researchers in the field consider developing a core outcome set to streamline future research. Randomization was proven to be safe and acceptable in this research field, and blinding of outcome assessors should be considered in the presence of patient-reported outcomes. The overall quality of the evidence was low to very low.
The evidence is current to May 2015. We included 20 studies from 1990 to 2011, enrolling 1652 adult participants hospitalized in the ICU, who were scheduled for planned tracheotomy. None of the studies were funded. The application of percutaneous techniques, does not reduce the rate of death, of serious, life-threatening complications (e.g. injuries to the windpipe or the oesophagus), major bleeding or problems with the tracheostomy tube (blockage, accidental loss, difficult tube change). There was some evidence that using percutaneous techniques results in fewer cases of wound infections (- 76%) and unfavourable scarring (- 75%). The quality of the evidence varied by outcome from moderate (wound infection) to low (death, serious complications, unfavourable scarring, problems with the tracheostomy tube) and to very low (major bleeding). Reasons for the limitations are: great differences among the studies, results not similar across the studies, and not enough data. Based on the available data, we conclude that percutaneous tracheostomies offer benefits for some of the outcomes when compared with surgical tracheostomies. However, because several groups of participants were excluded from the included studies (i.e. people with unfavourable neck structure, bleeding disorders or emergency situations), the number of participants in the included studies was limited, long-term outcomes were not evaluated, and data on participant-relevant outcomes were either sparse or not available for each study, the results of this meta-analysis are limited and cannot be applied to all critically ill adults.
We searched for clinical trials of physiotherapy up to 12 February 2015. We included 18 trials that had 739 participants with CRPS I. In most of these trials the participants had CRPS I of the arm and hand. We did not find any clinical trials that included participants with CRPS II. Overall we did not find any good quality clinical trials of physiotherapy aimed at reducing the pain and disability of CRPS I in adults. Most included trials were not well designed and contained only small numbers of patients. We did find some low quality trials suggesting that two broadly similar types of rehabilitation training, known as 'graded motor imagery' (GMI) and 'mirror therapy', might be useful for reducing the pain and disability associated with CRPS I after traumatic events or surgery or a stroke. From the limited evidence available it appears that some types of electrotherapy, such as ultrasound and pulsed electromagnetic field therapy, as well as a type of massage therapy known as manual lymphatic drainage, are not effective. Most studies did not report on adverse events and so we do not know if these treatments have any harmful side-effects. On the whole, because of the limited number and low quality of available trials for the various physiotherapy treatments, we cannot be sure if any of the physiotherapy treatments we evaluated are effective for treating the pain and disability of CRPS I in adults. It is possible that some treatments, such as GMI or mirror therapy, might be effective. Further high quality clinical trials of physiotherapy are needed in order to find out if any of the different types of physiotherapy treatment are effective at improving pain and disability in people with CRPS.
After searching for all relevant trials in scientific databases, we identified 13 randomised controlled trials (RCTs) published up to July 2014. We could extract and pool data from 12 RCTs, which involved 3720 participants (both genders), including children, adults (aged around 40 years) and older people from Finland, Spain, Sweden, the United States, Croatia, Chile, Thailand and Japan. Probiotics were found to be better than placebo in reducing the number of participants experiencing episodes of acute URTI by about 47% and the duration of an episode of acute URTI by about 1.89 days. Probiotics may slightly reduce antibiotic use and cold-related school absence. Side effects of probiotics were minor and gastrointestinal symptoms were the most common. The quality of the evidence is low or very low mainly due to poorly conducted trials, for example with unclear randomisation method and blinding. Some trials were supported by manufacturers of the tested probiotics and some trials had a very small sample size. Overall, we found probiotics to be better than placebo in preventing acute URTIs. However, more trials are needed to confirm this conclusion.
We found four trials. A trial with 27 participants compared the effects of azathioprine together with steroids to steroids alone for nine months. Azathioprine is a drug that is often used to treat autoimmune diseases because it suppresses the harmful immune cells. This trial had a parallel-group design, which means that the participants were divided into groups that each received only one of the treatments. A cross-over design trial with 10 participants compared the immune-regulating drug interferon (IFN) beta-1a with placebo (dummy treatment) for 12 weeks. The cross-over design means that all participants received both treatments in random order. A parallel-group trial with 67 participants also compared interferon beta-1a with placebo, but for 32 weeks. Another parallel-group trial with 60 participants compared the cytotoxic drug methotrexate with placebo for 40 weeks. The IFN beta-1a trials, but not the azathioprine or methotrexate trials, received pharmaceutical company support or sponsorship. None of these trials showed significant benefit or harm from the drugs. We selected disability scores as our primary measure of the effect of treatment. All the trials were too small to detect or rule out anything but major benefit or harm. We rated the quality of the evidence as moderate or low for IFN beta-1a and methotrexate because of problems with trial design, and because the small number of participants made the result imprecise. We rated the quality of the evidence for azathioprine as low because of lack of blinding and imprecision. Observational studies of these and other drugs, including the cytotoxic drugs cyclophosphamide, ciclosporin, mycophenolate, rituximab, alemtuzumab and natalizumab, peripheral blood stem cell transplantation, and the immune regulating drug interferon (IFN) alfa, exist but are of insufficient quality to determine whether any of these treatments are beneficial. The evidence is up to date to May 2016.
We searched for randomised controlled trials comparing zuclopenthixol with placebo in 2013. We found only two studies with 65 participants which could be included in this review. Overall the quality of these studies was low, with small numbers of people and significant bias. The studies were old, from 1968 and 1972, and would be unlikely to pass modern peer review standards. Only short-term information and data could be found, and only about zuclopenthixol dihydrochloride. The information is very limited but suggests that zuclopenthixol can lead to improvement in global state in comparison with placebo. However, there is also increased risk of side effects such as sedation,and tiredness. Given the low quality of information and age of the two studies, further research is needed, particularly further research on zuclopenthixol compared to newer and more recent antipsychotic drugs.
We looked for studies that included adult men and women who were current smokers and had a diagnosis of COPD. We included studies that assessed the effectiveness of any behavioural support or medication, or both as an aid to quit smoking. We included studies that compared different types of treatment or compared treatment to stop smoking with no treatment or 'usual care'. We only included studies that reported how many people had stopped smoking after at least six months of follow-up. We carried out the most recent search for studies in March 2016. We found high-quality evidence from a collection of four (1,540 participants) of the total 16 included studies (13,123 participants) in this review. Overall, we found evidence that smokers with COPD who receive a combination of high-intensity behavioural support and medication are more than twice as likely to quit as people who receive behavioural support alone. We found no clear evidence that one particular form of behavioural support or medication is better than another. It is still unclear whether smokers with COPD are different from smokers without COPD with regard to which treatments work best to help them stop smoking. We are quite confident in the finding that a combination of behavioural support and medication works better than behavioural support alone. However, we were not able to combine the results of many of the studies because the treatments or the outcomes of the studies were too different from each other.
This review identified five randomised controlled trials, involving 756 participants, which evaluated psychosocial interventions for the prevention of disability following traumatic injury. No convincing evidence was found supporting the efficacy of these interventions. In particular, self-help booklets and interpersonal therapies had no effect on preventing disability. There was some evidence that a more complex intervention involving collaborative care reduced symptoms of depression and PTSD in the short but not the medium term. There was evidence from three trials that psychosocial interventions had a detrimental effect on mental health. Taken together, our findings cannot be taken as supporting the provision of psychosocial interventions to prevent aspects of disability arising from physical injury. These results suggest that future interventions should focus on screening patients at risk of poor outcomes and only treating those who develop subsequent problems. However, the strength of these conclusions is limited by the small size and varied nature of many of the trials, which means that their results cannot be pooled.
In the studies, aerobic exercises were done for at least 20 minutes once a day (or twice for at least 10 minutes), 2 to 3 days a week. Strength training was done 2 to 3 times a week and with at least 8 to 12 repetitions per exercise. The exercise programs lasted between 2 ½ to 24 weeks. When compared to no exercising, aerobic exercise training may: - improve overall well-being by 7 points on a scale of 0 to 100. - improve ability to perform aerobic exercise; by using 2.8 ml/kg/minute more oxygen when walking on a treadmill. - increase the amount of pressure that can be applied to a tender point by 0.23 kgs/cm2 before the onset of pain. - reduce pain by 1.3 on a scale of 0 to 10. - have unknown effects on fatigue, depression or stiffness. These results are based on moderate quality evidence. Best estimate of what happens to people with fibromyalgia who take part in strength training: When compared to no exercise, strength training may: - reduce pain by 49 fewer points on scale of 0 to 100. - improve overall well-being by 41 points on a scale of 0 to 100. - lead to 2 fewer active tender points on a scale of 0-18. These results are based on low quality evidence. The numbers given are our best estimate. When possible, we have also presented a range because there is a 95 percent chance that the true effect of the treatment lies somewhere within that range.
This review included five randomised controlled studies with an overall total of 2187 women, the studies were at low or unclear risk of bias although it was not possible to "blind" women and staff to this intervention. Results showed that if ECV is done near the middle of the third trimester (32 to 34 weeks), it increases the chances that the baby will be lying head down at full term. Three trials including 1888 women found that beginning ECV at between 34 and 36 weeks compared with beginning ECV after 37 weeks (at term) had a 19% decrease in the rate of non-cephalic presentation at birth, a 10% reduction in the risk of failing to achieve a cephalic vaginal birth, and a considerably reduced chance of a breech vaginal delivery, however, early ECV may significantly increase the chances of late preterm birth. The quality of the evidence for these outcomes was graded as high. The evidence on the possible advantages and disadvantages of early (before 37 weeks) external cephalic version (ECV) will require careful discussion with women about the timing of the ECV procedure so that they can make informed decisions.
Thirty-two studies were included in this review. However, only 22 studies, involving 2658 women, provided data for analysis, looking at interventions given prior to caesarean section for reducing the risk of aspiration. There were several different drugs and drug combinations being considered and the studies were generally of poor or questionable quality. Antacids (like sodium citrate), H2 receptor antagonists (like ranitidine), proton pump antagonists (like omeprazole), all reduced the acidity of the stomach contents. An antacid plus an H2 receptor antagonist also reduced acidity. In theory, a combination like this, where the antacid acts quickly and the H2 receptor antagonists takes a little longer, should protect at periods of greatest risk, i.e. the beginning and end of the procedure (i.e. intubation and extubation). More research is needed to identify the best combination of drugs and to check for possible adverse effects.
For Down's syndrome screening, where tests were carried out in the first and second trimester and combined to give an overall risk, we found that a test comprised of first trimester nuchal translucency and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A was the most sensitive test, detecting nine out of 10 pregnancies affected by Down's syndrome. Five per cent of pregnant women receiving a high risk test result based on this combination would not be affected by Down's syndrome. There were relatively few studies assessing these tests and therefore we cannot make a strong recommendation about the best test.Other important information to considerThe ultrasound tests themselves have no adverse effects for the woman, and blood tests can cause discomfort, bruising and, rarely, infection. However, some women who have a high risk screening test result, and are given amniocentesis or CVS have a risk of miscarrying a baby unaffected by Down’s. Parents will need to weigh up this risk when deciding whether or not to have an amniocentesis or CVS following a high risk screening test result.
We identified two small, relevant trials. All the women in these trials had a history of postnatal depression, but were not depressed or using antidepressants at the beginning of the studies. Both studies compared antidepressant medicine with placebo. Women started taking the medicine or placebo on the first day after giving birth. In the larger study (56 women), the antidepressant given to women was nortriptyline, which is a tricyclic antidepressant. In the other study (25 women), the antidepressant used was sertraline which is a selective serotonin reuptake inhibitor (SSRI); these types of antidepressants work in different ways. The women and the researchers assessing the outcomes in both studies did not know which women were taking antidepressants and which placebo (i.e. both studies were 'double-blind'). Both studies were funded by the National Institute of Mental Health (NIMH), a US government organisation. There was no evidence that nortriptyline prevented postnatal depression. During the 17-week treatment period, 6 of the 26 women taking nortriptyline experienced postnatal depression compared with 6 of the 25 women taking placebo. One woman taking nortriptyline developed mania (a state of abnormally high arousal and energy level), and constipation was more common among women taking nortriptyline, but other unwanted, or harmful, effects did not differ between groups. In the sertraline study, 1 of the 14 women taking sertraline developed postnatal depression compared with 4 of the 8 women taking placebo (during the 17-week treatment period). This study was very small, so we can't be sure whether the difference between sertraline and placebo is due to chance, or whether sertraline does prevent postnatal depression among women with a history of postnatal depression. One woman taking sertraline experienced a hypomanic episode (a state like mania but less severe); and dizziness and drowsiness were more common among women taking sertraline than women taking placebo. This evidence is current to February 2018. We could only identify two relevant studies, which had small numbers of participants and inconsistent findings, and were conducted by the same research group. Therefore we consider the quality of evidence in this review to be very low. Further studies with larger samples are needed before we can know whether antidepressants can prevent postnatal depression. It is worth noting that no new relevant trials have been completed in the 10 years since we last examined this evidence. It may be useful for future medical studies to investigate whether antidepressants can prevent depression during pregnancy as well as during the postnatal period; and whether women who continue to take antidepressants during pregnancy (compared with stopping medication) are less likely to have a relapse of depression at this time. We also need studies which have longer follow-ups periods; examine outcomes and side effects for both the mother and fetus or breastfeeding infant; and compare antidepressants with other preventative interventions (such as psychological therapies).
The four studies in this review included 634 patients with AHFS and employed two types of nitrates (isosorbide dinitrate and nitroglycerin). The studies compared nitrates with frusemide and morphine, frusemide alone, hydralazine, prenalterol, intravenous nesiritide and placebo. The study population in the trials was predominantly male (469/634 or 74% of all the patients included in the studies were male). The findings of this review indicate that there is no significant difference between nitrates and alternative treatment interventions for patients with AHFS in terms of healthcare outcomes. Nitrates appeared to be well tolerated in all four studies. Headaches is the most common side effect reported by patients. Headaches occurred more frequently when compared with nesiritide. There appeared to be no significant difference in the occurrence of symptomatic hypotension, pain, nausea and angina between patients administered nitroglycerin and nesiritide. The included studies did not report healthcare costs as an outcome measure. The limitations of the review include the following: there were few studies eligible for inclusion (only four); the quality of the studies were relatively poor; the study participants were predominantly male; and all the eligible studies were conducted in developed Western countries. Consequently, the findings may not be generalisable to other healthcare settings and to females. The review also found no consistent evidence to support a difference in AHFS patients receiving nitrates or alternative interventions with regard to many of the healthcare outcome measures studied. Due to these limitations, the results of the review preclude definitive conclusions regarding the effectiveness and safety of nitrates compared with alternative interventions in the treatment of patients with AHFS.
We found 44 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) comparing diet, physical activity and behavioural (where habits are changed or improved) treatments (interventions) to a variety of control groups delivered to 4781 overweight or obese adolescents aged 12 to 17 years. Our systematic review reports on the effects of multidisciplinary interventions, dietary interventions and physical activity interventions compared with a control group (no intervention, 'usual care,' enhanced usual care or some other therapy if it was also delivered to the intervention group). The adolescents in the included studies were monitored (called follow-up) for between six months and two years. The average age of adolescents ranged from 12 to 17.5 years. Most studies reported the body mass index (BMI). BMI is a measure of body fat and is calculated by dividing weight (in kilograms) by the square of the body height measured in metres (kg/m2). We summarised the results of 28 studies in 2774 adolescents reporting BMI, which on average was 1.18 kg/m2 lower in the intervention groups compared with the control groups. We summarised the results of 20 studies in 1993 adolescents reporting weight, which on average was 3.67 kg lower in the intervention groups compared with the control groups. BMI reduction was maintained at 18 to 24 months of follow-up (monitoring participants until the end of the study), which on average was 1.49 kg/m2 lower in the intervention groups compared with the control groups. The interventions moderately improved health-related quality of life (a measure of a person's satisfaction with their life and health) but we did not find firm evidence of an advantage or disadvantage of these interventions for improving self-esteem, physical activity and food intake. No study reported on death from any cause, morbidity (illnesses) or socioeconomic effects (such as days away from school). Three studies reported no side effects, one reported no serious side effects, one did not provide details of side effects and the rest of the studies did not report whether side effects occurred or not. We identified 50 ongoing studies which we will include in future updates of our review. This evidence is up to date as of July 2016. The overall quality of the evidence was rated as low for most of the outcomes (results) measured, mainly because of limited confidence in how studies were performed, inconsistent results between the studies and the way that some outcomes used do not capture obesity outcomes directly. Also, there were just a few studies for some outcomes, with small numbers of included adolescents.
We reviewed the evidence about the effect of specific tools, called decision aids, which aim to improve decision making in the informed consent process for people who are considering participating in a clinical trial. These tools were compared to the standard process used for informed consent in clinical trials. There is currently not enough evidence to draw conclusions about the effectiveness of decision aids in the informed consent process for clinical trials. In clinical trials, one healthcare treatment is compared to another treatment or to no treatment. Before potential participants sign a consent form where they agree to take part in a clinical trial they must be given information about what will be expected of them and what they can expect. Research has shown that this information is often not as good as it could be. For example, people often misunderstand the information they have been given. Decision aids, which are tools that assist people to think about what matters most to them, support decision making for treatment and screening. Presenting information about trial participation through decision aids might improve the informed consent process by improving participants' knowledge, certainty with the decision and enabling them to consider what matters most to them personally. We searched the literature for studies where potential trial participants were randomly allocated to receive decision aids, compared to no decision aids or to other types of information for informed consent. We found one study, which reported data from two separate decision aid trials, where people who were given a decision aid alongside standard information were compared to people who were given standard information alone. When data from these two trials were combined, the results were inconclusive and not able to show whether people given the decision aid had any more or less knowledge or uncertainty about their decision, or were more or less likely to participate in a trial, than the people who were only given standard information. However, people who used the decision aid may have felt less regret about their decision. Overall there was very low quality evidence to support these findings, which means that there may be uncertainty around the results, and therefore, further research is required.
The review included two trials with 69 people (aged one to 55 years) with severe haemophilia with inhibitors. Both trials compared recombinant factor VIIa with activated prothrombin complex concentrate and people were selected for one treatment or the other randomly. We found two clinical trials comparing Novoseven®and FEIBA®. The trials did not show a difference in how well the two products worked and both were tolerated equally well with no clotting complications. We conclude that both recombinant factor VIIa and plasma-derived concentrates can be used to treat bleeds in people with haemophilia and inhibitors. There were some major problems with regards to the way both trials were designed, in relation to knowing which treatment group each person was in (both before the trial was started and during) and also how missing results were handled.
We identified three studies. Our most recent search for studies was done in January 2014. One trial compared voriconazole to liposomal amphotericin B in 849 men and women (58 deaths) with cancer and a poor immune system. Treatment was most often given for seven days. The treatment was provided in patients where a fungal infection was suspected because they had a fever that could not otherwise be explained. The second trial compared voriconazole to amphotericin B deoxycholate in 391 men and women (98 deaths) with cancer and a poor immune system. Voriconazole was given for 77 days on average whereas liposomal amphotericin B deoxycholate was given for 10 days on average. The treatment was given when patients were known or suspected to have a specific fungal infection (Aspergillus). The third trial compared voriconazole to fluconazole in 600 men and women (the number of deaths was not stated) with cancer who had undergone a transplantation of their bone marrow after high-dose chemotherapy that suppresses their immune system. The treatment was given to prevent fungal infections. All studies were sponsored by the manufacturer of the study drug, voriconazole. This review found that voriconazole was inferior to liposomal amphotericin B for treatment of suspected fungal infections. More patients treated with voriconazole died and a claimed benefit in terms of fewer new fungal infections disappeared when we included patients that had been excluded without good reason from the analyses presented in the published article. We also found that voriconazole has not been compared with amphotericin B when given under optimal conditions for the treatment of invasive aspergillosis, and that voriconazole was no better than fluconazole in patients undergoing a bone marrow transplantation for preventing invasive fungal infections or for extending the time patients survive without a fungal infection. The first and second trial were seriously misleading. The first trial analysed the results of the study in a different way from that originally planned, which favoured the study drug voriconazole. The second study compared voriconazole to a drug (liposomal amphotericin B) that was given at substandard dose, which means the results of the study are not meaningful. The third study should have presented how many patients died but did not.
People with cancer undergoing treatment often have many psychological and physical adverse effects as a result of their cancer and the treatment for it. They also experience poorer quality of life because of the disease and its treatment. Some studies have suggested that exercise may be helpful in reducing negative outcomes and improving the quality of life of people with cancer who are undergoing treatment. Also, a better quality of life may predict longer life. This review looked at the effect of exercise on health-related quality of life and areas of life that make up quality of life (e.g. tiredness, anxiety, emotional health) among people with cancer who are undergoing treatment. The review included 56 trials with a total of 4826 participants. The results suggest that exercise may improve overall quality of life right after the exercise program is completed. Exercise may also improve the person's physical ability and the way the person can function in society. Exercise also reduced tiredness at different times during and after the exercise program. The positive effects of exercise were greater when the exercise was more intense. No effects of exercise was found in the way a person views his or her body, on the person's ability to think clearly, the person's mood, feeling of pain, and on the way the person views his or her spiritual health. However, these findings need to be viewed with caution because this review looked at many different types of exercise programs, which varied by type of setting, length of the program, and how hard the trial participants had to exercise. Also, the investigators used a number of different ways to measure quality of life. There is a need for more research to understand how to maintain the positive effects of exercise over a longer period of time after the exercise program is completed, and to determine which parts of the exercise program are necessary (i.e. when to start the program, type of exercise, length of the program or exercise session, how hard to exercise). It is also important to find out if one type of exercise is better for a specific cancer type than another for the maximum effect on quality of life.
We searched the literature until 2 May 2019 to find randomised controlled trials (RCTs), quasi-RCTs, cluster-RCTs and cross-over RCTs of work-break interventions aimed at preventing work-related musculoskeletal disorders at work. We analysed all relevant studies to answer the research question and found six studies involving 373 workers, the majority of whom were female (≥ 78%), with a follow-up period of two to 10 weeks. Key results Effect of different work-break frequencies Five of the six studies evaluated different work-break frequencies. The implementation of additional work breaks (three studies) may not have an effect on musculoskeletal pain, discomfort or fatigue when compared to no additional work breaks or work breaks taken as needed. Additional work breaks (three studies) may have a positive effect on productivity and work performance when compared to a conventional work-break schedule. Additional higher frequency work breaks have been compared with additional lower frequency work breaks in one study, which resulted in no differences in participant-reported musculoskeletal pain, discomfort and fatigue, nor in productivity and work performance. Effect of different work-break durations None of the studies evaluated the effect of duration of work breaks. Effect of different work-break types Two of the six studies evaluated different work-break types. Active work breaks (one study) may not reduce nor increase the incidence of participant-reported musculoskeletal pain, discomfort and fatigue, or productivity and work performance. Similarly, different active work breaks have been compared with one another (one study), i.e. relaxation and physical active work breaks, which revealed no differences in participant-reported musculoskeletal pain, discomfort and fatigue, nor in productivity and work performance. Conclusions At present, we conclude that there is very low- to low-quality evidence that different work-break frequencies and types may not considerably reduce the incidence of musculoskeletal disorders. Although the results suggest that there may be a positive effect of different work-break frequencies on productivity and work performance, there is a need for high-quality studies with large enough sample sizes to assess the effectiveness of different work-break interventions. Furthermore, work-break interventions should be reconsidered, taking into account worker populations other than office workers and the possibility of combining work-break interventions with other interventions such as ergonomic training or counselling, which may possibly prevent musculoskeletal disorders.
In this review, the analysis of the two eligible trials found that the data was insufficient to reach a conclusion regarding the effectiveness of the 36-hr continuous infusion method. The blood flow lowering side-effects of indomethacin were reduced by the continuous infusion method, but there was insufficient data to recommend this administration method versus the traditional method.
In this review we are able to show that small weight loss is possible with selective pharmacological or non-pharmacological interventions but it is difficult to be sure of the results because the studies were small and compared different interventions over different time periods.
The drug aminophylline has also been used intravenously (injected into the veins) for many years; however, this review of trials found that aminophylline is not significantly better than other bronchodilator drugs, and has more adverse effects. For every 100 people treated with aminophylline an additional 20 people had vomiting and 15 people arrhythmias or palpitations. This review was first published in 2000 and was updated in 2012 and the addition of two trials in 2012 did not alter the original conclusions.
This review of 23 trials involving 3043 women with endometriosis has shown that there no evidence of benefit with the use of ovulation suppression for women with endometriosis and infertility. Endometriosis is caused by the lining of the uterus (endometrium) spreading to a site outside the uterus. It is associated with subfertility and can cause pain during both sexual intercourse and menstruation. The hormone oestrogen stimulates the growth of endometriosis. For many years, the use of drugs such as danazol to stop ovulation and the production of oestrogen has been standard practice in the treatment of pain and subfertility caused by endometriosis. This works well for pain, but does not appear to improve fertility. In fact, as ovulation and periods are stopped for the time of treatment, fertility may be reduced by this approach.
The results of the existing trials suggest that this may be effective, but the evidence is not conclusive because most of the studies of this approach have methodological problems. A recent laboratory study also suggests that the method has an active ingredient. Further research may be worthwhile.
This review includes nine randomized trials with a total of 484 participants. The limited data available suggest that rectal 5-ASA is effective and safe for maintenance of remission in UC. Rectal 5-ASA was found to be superior to placebo (e.g. enema or suppository with no active medicine). There was no difference in the incidence of side effects between rectal 5-ASA and placebo groups. Side effects were generally mild in nature and common side effects included anal irritation and abdominal pain. Studies comparing rectal 5-ASA with oral 5-ASA (pills) found no differences in effectiveness for maintenance therapy. Well designed randomized trials are needed to investigate different doses of rectal 5-ASA for maintenance therapy, Future studies should assess the effectiveness of combination therapy of oral 5-ASA with rectal 5-ASA as this has been found to be effective in active UC and has not been investigated for maintenance therapy. Future studies should also compare rectal 5-ASA with rectal corticosteroids.
We included trials up to July 2013 in our review. We re-ran the searches in February 2015. In total there are 17 studies awaiting classification. We included 66 studies with 7840 participants, both male and female, and including children and adults. Most of these participants were undergoing various planned surgical procedures in hospitals in several countries including Korea, Turkey and India. The trials compared an intervention aiming to reduce pain on injection with a placebo to ascertain whether any intervention was effective at reducing pain. The outcome was assessed by recording the level of pain reported by patients when injected with rocuronium bromide. The most studied treatments were injection of the local anaesthetic lidocaine, or the painkillers fentanyl or remifentanil, into the vein before injecting rocuronium. These treatments may reduce the pain associated with injecting rocuronium, but the evidence is of low quality. Some interventions, for example using painkillers such as fentanyl, may increase cough, chest tightness and breath holding. These are recognized side effects of these drugs. The low quality of the evidence for the assessment of changes in the level of pain was due to inadequate reporting of study design and variation in the study results. In addition to these limitations, for some adverse event outcomes we did not have enough information to be certain about the average effect. Further research is needed with high quality, well designed studies to determine whether pain on injection of rocuronium bromide can be reduced by using an appropriate intervention.
This review aimed to identify whether single-dose antibiotic treatments are as effective as longer ones for maternal and newborn outcomes. In general, the risk of bias of trials included in this review was largely unclear. The overall quality of the evidence was assessed using the GRADE approach. The review of 13 studies, involving over 1622 women, found that a seven-day regimen is more effective than a one-day course, especially for the outcome of low birthweight (high quality evidence), but this result is based on just one study. There were no clear differences between a single dose and a four- to seven-day short course of antibiotics for other review outcomes, including kidney infection (very low quality evidence) and preterm birth (moderate quality evidence). Women with a single-dose regimen reported fewer side effects (low quality evidence). More trials are needed to confirm which length of treatment is best for women and babies.
The evidence is current up to 10 April 2017. We included eight studies with 1157 ICU patients and 943 carers of ICU patients. Seven studies are awaiting classification because we could not assess their eligibility, and three studies are ongoing. We included studies that assessed information given to patients or their carers compared to no information, and studies that assessed information as part of a more complex intervention compared to a complex intervention that did not include information or education. Studies included varied information: standardised or tailored to the individual, given regularly or on a single occasion, and that included verbal or written information, audio recordings, multimedia information, and interactive information packs. Overall, it is uncertain whether information or education (given alone or as part of a more complex intervention) improves outcomes for patients and their carers following a stay in the ICU. For patients, it is uncertain whether or not information or education reduces anxiety or depression, or improves health-related quality of life. One patient asked to withdraw from the study because they believed that their mental health worsened when they completed a questionnaire to assess anxiety and depression, but it is not clear whether this person received the information intervention or not. No studies reported PTSD in patients. For carers, it is uncertain whether or not information or education reduces anxiety or depression or improves carers' knowledge acquisition or their satisfaction with information provided. It was not possible for researchers to mask patients and carers to the intervention they received, and it was unclear whether this would affect the results, which relied on self assessments. Study authors did not consistently report rigorous methods for carrying out randomised trials, and we noted some losses of patients and carers during the studies. We found few small studies for this review, reporting limited data for many outcomes of interest. It is uncertain whether information or education is effective due to very low-certainty evidence. We are uncertain about the effects of information or education interventions given to adult ICU patients and their carers. The evidence was of very low certainty, and our confidence in the evidence was limited. We are aware of three ongoing studies and seven studies that were recently completed but not yet published. These studies may provide additional evidence or improve the certainty in the findings in future updates of the review.
This review identified four studies (enrolling 2177 people). Three studies compared ACEi to placebo or no treatment and one study compared ACEi to ARB. There is not enough evidence in the published literature at present to determine how effective drugs in the ACEi or ARB families are for treating patients with early (stage 1 to 3) CKD who do not have diabetes.
Seventeen trials were included. These involved 1433 patients, who were mostly young physically active adults. All included trials had methodological weaknesses that are likely to undermine the reliability of their results. Data for pooling individual outcomes were available for a maximum of nine trials. There was not enough evidence of differences between two groups in terms of functional knee scores, adverse effects and complications (infection, hardware problem such as pain from fixation device, graft failure), range of motion (flexion and extension deficit). At long term follow-up, some clinician-assessed measures of knee stability and repeated rupture rate or occurrence of new meniscal injuries were better after double-bundle reconstruction. We concluded that there was not enough evidence to say whether double-bundle reconstruction gives better results than single-bundle reconstruction for anterior cruciate ligament rupture in adults. However, there is limited evidence that double-bundle ACL reconstruction has some superior results for knee stability and protection against repeat ACL rupture or newly occurring meniscal injury.
We found one controlled trial that examined whether one gram per day of intravenous vitamin C would help in the treatment of tetanus patients. Vitamin C was used alongside standard treatments for tetanus. Intravenous vitamin C reduced the mortality of children aged between 1 and 12 with tetanus by 100% and that of 13 to 30 year old patients by 45%. The trial was not properly conducted and caution is required in the interpretation of the findings. Vitamin C cannot be recommended as a treatment for tetanus on the basis of this single study. Further investigation of the role of vitamin C in tetanus treatment is warranted.
Four trials with a total of 466 participants were reviewed, focusing on the comparison of 'short duration' and 'long duration' of AEDs drugs in people with a single cerebral lesion. These trials compared various durations of AED therapy: six to 12 months as short duration and 12 to 24 months as long-duration therapy. No statistically significant benefit of one duration of AED over the other (six, 12 or 24 months) could be demonstrated. In people with calcified cysts, longer duration of therapy may be preferable. All four included trials, enrolled people with a single brain lesion. The findings of our review cannot be extrapolated to people with multiple cysts or with cysts in unusual parts of the brain. The evidence is current to July 2019.
We reviewed five studies conducted to assess the effects of antiviral agents (medications that reduce the spread of virus in the body) on mortality and long-term complications of herpes disease in the newborn. Antiviral agents were shown to reduce mortality from the condition, but the reduction was not statistically significant due to the small number of infants in the study. There was insufficient trial data to guide caregivers regarding the duration of antiviral therapy or dose.
This review looked for evidence on how telerehabilitation interventions work in adults with MS. We searched widely for randomised controlled trials (RCTs), a particular kind of study where participants are placed in treatment groups by chance (that is, randomly) because in most settings these provide the highest quality evidence. We were interested in studies that compared a telerehabilitation programme with standard or minimal care, or with different kinds of rehabilitation programmes. We found nine relevant RCTs covering 531 participants (469 included in the analyses), evaluating a wide variety of telerehabilitation interventions in persons with MS. The telerehabilitation interventions evaluated were complex, with more than one rehabilitation component and included physical activity, educational, behavioural and symptom management programmes. These interventions had different purposes and used different technologies, so a single overall definite conclusion was not possible. The methodological quality of the included studies is low and varied among the studies. There was 'low-quality' evidence from the included RCTs to support the benefit of telerehabilitation in reducing short-term disability and managing symptoms such as fatigue in adults with MS. We found limited evidence to support the benefit of telerehabilitation interventions in improving disability, reducing symptoms and improving quality of life in the longer term. Furthermore, the interventions and outcomes being investigated in the included studies were different to each other. No studies reported any serious harm from telerehabilitation and there was no information on the associated costs. There is a need for further research to assess the effects of the range of telerehabilitation techniques and to establish the clinical and cost effectiveness of these interventions in people with MS. The evidence in this review is up to date to July 2014.
The evidence is current to August 2016. We included two trials, with 40 participants. Included trials assessed the effects of one type of NPPV called bilevel positive airway pressure, which lasted for two and 24 hours, respectively, in the two trials. Overall, we found that NPPV compared with no additional treatment, treatment as usual or placebo did not result in any benefit or harm regarding death from all causes, serious adverse events (i.e. major complications) or improvement in asthma symptoms. Five study participants did not tolerate the treatment, four because of discomfort and one because intubation was required. Current evidence cannot confirm or reject the effects of NPPV for treatment of children with acute asthma. Larger randomised clinical trials are warranted. The evidence behind our conclusions is of very low quality. The two studies had high risk of bias (i.e. the studies were conducted in a way that may skew results to the positive side). In addition, the two studies included few participants, making results of this review imprecise.
The review found 10 trials, which studied 375 women having six different types of needle suspension operations and compared them with 489 women who received other treatments. Most of the trials were small or of poor quality, making their results less reliable. More women were cured after abdominal operations such as colposuspension (84%) than after needle suspension (71%): both women who had and had not had a previous operation for incontinence. There was not enough evidence about complications, or how needle suspension compares with other operations. Needle suspension operations were not compared with conservative treatments such as pelvic floor exercises or drugs. In summary, needle suspension surgery appears to be less effective for urinary incontinence than abdominal surgery, and there is not enough evidence to compare it to other treatments.
We searched the Cochrane Pregnancy and Childbirth Group's Trials database for clinical trials assessing methods (interventions) of improving nipple pain among breastfeeding women in September 2014. We also looked at healing and infection of nipples, length of breastfeeding, if infants only received breast milk, and if mothers were happy with treatment for nipple problems and breastfeeding in general. Interventions included drug treatments (against bacteria given by mouth, spray, ointment; against fungal infections), non-drug treatments (lanolin, petroleum jelly, peppermint oil, glycerine), dressings, nipple protectors (breast shields or shells), light treatment, or applying expressed breast milk. Interventions were compared with each other or usual care (control). We found four trials of good methodological quality involving 656 women, which evaluated five different interventions including glycerine pads, lanolin with breast shells, lanolin alone, expressed breast milk, and an all-purpose nipple ointment. All studies included education to position the infant at the breast correctly as part of routine care to both intervention and control groups. Currently, there is not enough evidence to recommend any specific type of treatment for painful nipples among breastfeeding women. These results suggest that applying nothing or expressed breast milk may be equally or more beneficial in the short-term experience of nipple pain than the application of an ointment such as lanolin. One important finding in this review was that regardless of the treatment used, for most women, nipple pain reduced to mild levels approximately seven to 10 days' after giving birth (postpartum). The quality of the evidence for this review did not allow robust conclusions regarding treating nipple pain. We found only four small trials and all four trials compared varying interventions, participants, what was measured, and standards of usual care. While the methodological quality of the included studies was good, the overall quality of the evidence for the primary outcome of nipple pain was of low quality, mainly due to single studies with few participants contributed data for analysis.
This review summarising the evidence from randomised controlled trials included 11 trials with 1654 participants. Consistent with the general hip fracture population, most of the trial participants were older persons of around 80 years of age and the majority were female. Ten trials compared traction versus no traction and two trials, including one of the preceding 10 trials, compared skin and skeletal traction. As well as limitations in the trial methods, there were very limited data for pooling and a lack of information about the longer-term consequences of applying or not applying traction. Nonetheless, the evidence from the 10 trials consistently showed no evidence to support the supposed advantages of traction described above. There were inconclusive data for pressures sores (skin ulcers) and other complications. One trial reported three adverse effects (sensory disturbance and skin blisters) related to skin traction; all were minor.
This review identified five relevant studies, comprised of 341,342 participants in total. Two of the studies were assessed to be of low risk of bias, whilst the remaining three had more substantive methodological weaknesses. Meta-analysis of all five included studies demonstrated no statistically significant reduction in prostate cancer-specific mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.86 to 1.17). Meta-analysis of the two low risk of bias studies indicated no significant reduction in prostate cancer-specific mortality (RR 0.96, 95% CI 0.70 to 1.30). Only one study included in this review (ERSPC) reported a significant 21% relative reduction (95% CI 31% to 8%) in prostate cancer-specific mortality in a pre-specified subgroup of men. These results were primarily driven by two countries within the ERSPC study that had very high prostate cancer mortality rates and unusually large reduction estimates. Among men aged 55 to 69 years in the ERSPC study, the study authors reported that 1055 men would need to be screened to prevent one additional death from prostate cancer during a median follow-up duration of 11 years. Harms included overdiagnosis and harms associated with overtreatment, including false-positive results for the PSA test, infection, bleeding, and pain associated with subsequent biopsy.
Twelve studies were identified with 1020 women from 11 countries. Eight studies compared laparoscopy versus open appendicectomy, and four compared laparoscopy using a wait and see approach. The evidence is current to October 2013. In this review of randomised controlled trials, laparoscopy was found to be superior to both open appendicectomy alone and a wait and see strategy, as more specific diagnoses were made before discharge, and shorter hospital stays and earlier return to work (when compared with open appendicectomy only) were reported. No evidence was found of an increase in adverse events when any of these strategies was applied. The rate of removal of normal appendices was reduced with the laparoscopic approach compared with open appendicectomy but was greater when a laparoscopic approach was compared with a wait and see strategy. The quality of the evidence was ranked as low to moderate for most outcomes, mainly because many of the studies had methodological limitations and imprecision was noted for some outcomes.
We searched medical journals for reports of clinical trials which examined the effects of removing white blood cells from donated blood. We were interested in finding out whether the removal of white blood cells from donated blood resulted in patients receiving a blood transfusion having few complications such as transfusion-related acute lung injury, death, infectious and non-infectious complications, or any other adverse event. We included people of any age or sex, who received a blood transfusion for any reason. The evidence is based on studies retrieved up to 05 December 2014. We found 13 studies which included people who received a blood transfusion during heart or cancer surgery, or because they were injured, had cancer, HIV or sepsis. We found no clear evidence showing either benefits or harms for removing white blood cells from donated blood. For all of the outcomes examined (transfusion-related acute lung injury, death from any cause, infection from any cause, non-infectious complication or any other adverse event), there was no sign of benefit or harm. The overall quality of evidence of the included studies ranges from very low to low. None of the studies included enough people to give a definitive answer about the usefulness of removing white blood cells from donated blood. New high-quality studies, involving a few thousand people, are needed to enable us to know the true benefits and harms of this procedure.
The evidence to support treatments for preventing lactation is limited. The review authors identified 62 controlled trials that randomised a total of 6428 mothers to receive the treatment under investigation, no treatment or another treatment. Twenty-two trials did not contribute data to the meta-analyses. The trials were generally of limited quality and most were conducted among healthy women who chose not to breastfeed for personal reasons at hospitals in industrialised countries before 1980. Half of the trials involved bromocriptine. Two trials (107 women) reported that taking bromocriptine was better than no treatment in suppressing lactation in the first week after giving birth. The 11 trials using oestrogen preparations (diethylstilbestrol, quinestrol, chlorotrianisene, hexestrol) also showed suppression of lactation. A combination of testosterone and oestrogen preparations was of some benefit in reducing symptoms in three trials (436 women). Other pharmacologic agents (clomiphene, tamoxifen, prostaglandins, pyridoxine, oxytocin, L-dopa and homeopathic preparation) were tested in single small trials. Generally, side effects were poorly reported and no case of thromboembolism was recorded among trials that included it as an adverse treatment outcome. Most of the drugs tested are currently not available or registered for suppressing lactation. No trials compared non-drug approaches with no treatment and none of the included trials provided reliable data on women’s satisfaction with the treatment.
This review of existing clinical trials was carried out by authors working with the Cochrane Oral Health Group and updates the previous version published in 2010. The evidence is current up to 31 December 2014. In this review there are 35 trials (including 2565 participants), published between 1997 and 2014, where people randomly received a type of gum disease treatment (including scaling and root planing (SRP) and SRP combined with other types of treatment), or usual care/no active treatment. The trials included in this review used SRP with, or without, an additional treatment. Additional treatments included instructions for cleaning teeth properly (known as oral hygiene instruction (OHI)), and other gum treatments (for example, antimicrobials, which are used to treat infections). We found 35 trials that were suitable for inclusion in this review. Thirty-four of those studies provided results that could be included in at least one of the two comparisons. 1. The evidence from 14 trials (1499 participants) showed that SRP reduces blood sugar levels in diabetic patients by 0.29% up to 4 months after receiving care when compared with usual care/no active treatment. After 6 months, there was no evidence that this reduction was sustained. 2. The evidence from 21 trials (920 participants) investigating different types of gum disease treatments failed to show that one treatment was better than another. There were not enough studies measuring side effects to be able to show if gum disease treatments cause any harm. Currently there is low quality evidence to support using scaling and root planing for controlling blood sugar levels up to 4 months after receiving treatment. Ongoing gum disease treatment is advised to maintain improvements in blood sugar levels.
Two randomized controlled trials, involving a total of 122 athletes with exercise-related groin pain, were included in this review. Participants were aged between 18 and 50 years and all but one were male. They had had groin pain for at least two months. One trial demonstrated positive results in athletes treated by exercise therapy (strengthening of hip and abdominal muscles, and training muscular co-ordination) in comparison with 'conventional' physiotherapy consisting of passive modalities (stretching exercises, electrotherapy and transverse friction massage) 16 weeks after the end of treatment, for 'successful treatment' (based primarily on pain measures) and for the rate of return to sports at the same level without groin pain. The second study compared multi-modal treatment (heat, manual therapy and stretching) with exercise therapy and found no significant difference between groups for 'successful treatment' and return to sports, but did show an earlier return to sport for those athletes who achieved this outcome following the multi-modal treatment. The available evidence is exclusively related to athletes and is limited because of the low number of studies and low number of participants for each outcome. Further randomized controlled trials are needed to ratify these results.
We included six small trials involving 899 children aged 12 months to 18 years conducted in Iran, Israel, the USA, Brazil, and Kenya. This update included three new trials conducted between 2007 and 2016 that involved 331 children. Two studies were supported by pharmaceutical manufacturers; one by a university research centre; one by the Honey Board of Israel and non-government agencies; and one by USA National Honey Board. One study did not report funding sources. We compared honey to over-the-counter cough preparations, bromelin (a pineapple enzyme) mixed with honey, fake treatment (placebo), and no treatment. Honey probably reduces cough symptoms more than placebo and salbutamol (a drug that opens lung airways) when given for up to three days. Honey is probably more effective at providing cough relief and reducing the impact of cough on children's sleep at night than no treatment. There may be little or no difference between the effects of honey and dextromethorphan (an ingredient in over-the-counter cough remedies) or honey and bromelin with honey on all cough symptoms. Honey may be better than diphenhydramine (an antihistamine) at relieving and reducing children's cough. The parents of seven children given honey and two given dextromethorphan reported side effects in their children, such as not falling asleep easily, restlessness, and becoming overexcited. The parents of three children in the diphenhydramine group reported that their children were often sleepy. The parents of nine children given salbutamol, seven given honey, and six given placebo reported diarrhoea. The parents of four children who received salbutamol and one child given honey reported rash. We found no evidence for or against the use of honey to relieve cough in children. Using honey for infants aged up to 12 months is not advised because of poor immunity against bacteria that may be present, which can cause paralysis. Most of the children received honey for just one night, which is a limitation to the results of this review. Overall, evidence quality was low to moderate. Some studies did not blind participants.
Cochrane reviews of randomised controlled trials that examined the effectiveness and safety of medications for alcohol withdrawal syndrome were included in this overview. Participants in the review studies varied in age, gender, nationality, severity of symptoms and treatment as outpatients or inpatients. Five reviews, 114 studies, 7333 participants, were included. We considered the efficacy of the medication on alcohol withdrawal seizures, adverse events as a measure of safety and acceptability of the treatment as dropouts from the study. These outcomes were considered in 72 of the 114 studies. The treatments used were sedative benzodiazepines, anticonvulsants, baclofen, GHB and PAN. Baclofen and GHB mimic alcohol effects and can rapidly reduce symptoms. PAN (psychotropic analgesic nitrous oxide) involves administering low levels of nitrous oxide and oxygen gases so that the individual remains conscious and coherent. Comparing the five treatments with placebo, benzodiazepines performed better for seizures (three studies, 324 participants, moderate quality of evidence). This was the only treatment with statistically significant findings. Data on potential harms were sparse and fragmented in these studies. Benzodiazepines also performed better than antipsychotics for seizures (4 studies, 633 participants, high quality of evidence). For the majority of our results, further research is likely to have an important impact on confidence in the estimate of effect. We assessed the quality of the evidence in the included reviews using GRADE, which looks at the quality of evidence for each outcome, taking into consideration the magnitude of the effect, the relevance of the data to the clinical question being asked, the sample size in the relevant trials, the methodological quality of the trials and the consistency of the findings.
Flexible working arrangements, such as flexitime and teleworking, are becoming more common in industrialised countries but the impacts of such flexibility on employee health and wellbeing are largely unknown. This review examined the health and wellbeing effects of flexible working arrangements which favour the worker as well as those dictated by the employer (for example, fixed-term contracts or mandatory overtime). Ten controlled before and after studies were found which evaluated the effects of six different types of flexible working arrangement on employee health and wellbeing: self-scheduling (n = 4); flextime (n = 1); overtime (n = 1); gradual retirement (n = 2); involuntary part-time (n = 1) and fixed-term contract (n = 1). Self-scheduling of shift interventions and employee controlled partial/early retirement were found to improve health (including systolic blood pressure and heart rate; tiredness; mental health, sleep duration, sleep quality and alertness; and self-rated health status) and/or wellbeing (co-workers' social support and sense of community) and no ill health effects were observed. The studies of overtime working, flexitime and fixed-term contracts found no significant effects on physical, mental or general health or on any of the wellbeing outcomes examined. Importantly, however, the study on overtime failed to provide detailed information on either the amount or duration of overtime worked, so it is therefore difficult to draw any conclusions regarding the effects of overtime on workers' health and wellbeing. Overall, these findings seem to indicate that flexibility in working patterns which gives the worker more choice or control is likely to have positive effects on health and wellbeing. However, given the small number of studies included in the review and their methodological limitations, caution should be applied to this conclusion. Well-designed studies are therefore needed to further explain the relationship between flexible working and health and wellbeing.
We found eight randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups in a random manner) where 387 people on sliding scale insulin therapy and 615 on mainly basal-bolus insulin treatment with type 2 diabetes could be analysed. The average length of hospital stay was between five and 24 days. Six studies compared sliding scale insulin with basal-bolus insulin; one study compared sliding scale insulin with basal insulin only; and the remaining study used continuous insulin infusion as the control group. The average age of participants was 44.5 years to 71 years. The evidence is up to date as of December 2017. The main comparison was between sliding scale insulin and basal-bolus insulin therapy with the following results. Of the four studies reporting deaths, one out of 268 participants in the SSI group compared with two out of 334 participants in the basal-bolus group died. Severe hypoglycaemic episodes, defined as blood glucose levels below 40 mg/dL, occurred in 5 per 1000 people in the sliding scale insulin groups compared with 24 per 1000 people in the basal-bolus insulin groups. These data are uncertain because further analyses showed neither a positive nor a negative effect comparing both insulin strategies. The length of hospital stay in the sliding scale insulin groups compared with the basal-bolus insulin groups was 0.5 days longer, again with further analyses indicating that this information is uncertain. The results for adverse events other than hypoglycaemic episodes, such as postoperative infections, did not indicate an advantage or disadvantage of either strategy. The average blood glucose level during hospital stay in the sliding scale groups was 14.8 mg/dL higher compared with the basal-bolus groups. We are uncertain about these data because analyses showed neither a positive nor a negative effect comparing both insulin strategies. No trial reported on deaths caused by diabetes as such or socioeconomic effects like costs of the interventions or absence from work. Overall, our confidence in the results for all analysed outcomes was low or very low mainly due to the low number of studies and participants and because the results were not precise, that is they could change in any direction once new studies are published.
This is an update of the review published in 2017. We examined the evidence from four trials of rPMS (three individual RCTs and one cross-over trial) involving a total of 139 participants. Two studies compared rPMS against 'sham' stimulation (a very weak stimulation or a sound only). Two studies compared rPMS plus rehabilitation versus sham plus rehabilitation. We found little evidence for the use of rPMS to improve activities of daily living, muscle strength, upper limb function, and spasticity (unusual stiffness of muscles) in people after stroke. Although one trial reported that rPMS reduced spasticity of the upper limb, the effect was small and remains unclear. We classified the quality of the evidence as low for improving activities of daily living, mainly because one study had a small sample size. It remains unclear whether use of rPMS is useful for improving activities of daily living and functional ability in people after stroke. More trials involving larger numbers of participants are needed to determine the effects of rPMS.
This review sought evidence that supplementing the diet of preterm and low birth weight infants with taurine improves their growth and development. Nine small trials were found, but these did not provide any evidence that providing extra taurine improved outcomes. However, further trials of taurine supplementation are not likely to take place since taurine is naturally present in breast milk and current standard practice is to add taurine to formula milk and to intravenous nutrition solutions for feeding preterm and low birth weight infants.
Limitations: Heterogeneity among the analysed mantle cell lymphoma trials precluded reliable assessment of efficacy of R-chemo with respect to overall survival. Variability in treatment regimens among trials precluded determination of which chemotherapy regimen is the best to combine with rituximab or about the optimal number of cycles needed to treat patients with indolent lymphoma.  Future directions: From our view future studies should focus on the following points:  1. Which standard chemotherapy should be used in combination with Rituximab  2. Influence of clinical and biologic prognostic markers after R-chemotherapy. What is similar and what is different  3. Understanding rituximab efficacy and resistance  4. Role of rituximab in treatment of progressive disease  5. Mechanism of rituximab in combination with chemotherapy  6. Role of Pharmacokinetic, pharmacogenetics in the treatment with R-chemo  7. Role of subsequent therapy with rituximab after R-chemo
This review looked at the effectiveness of treatments for ELP and included 15 studies, with 473 participants with ELP. All involved oral, but not genital, disease. Many studies were excluded either because they were not randomised controlled trials (where participants are divided into two groups at random) or because they recruited participants with all types of lichen planus, rather than just the erosive subtypes. All of these studies recruited small numbers of participants (12 to 94) and used a variety of different assessment methods and timings; hence, it was not possible to combine or compare results between studies directly. We found only weak evidence for the effectiveness of any of the treatments for oral ELP. None of the studies involved genital or oesophageal disease; hence, no evidence was found for the treatment of these conditions. One small study found that 0.025% clobetasol propionate (a very potent topical steroid) administered as a spray significantly reduced pain when compared to ointment. In another study, a significant difference in pain was seen in the small subgroup of 11 ELP participants, favouring ciclosporin solution over 0.1% triamcinolone acetonide in orabase (a potent topical steroid). In a study involving 45 ELP participants, aloe vera gel was 6 times more likely to result in at least a 50% improvement in pain symptoms compared to placebo. In a study involving a small subgroup of 8 ELP participants, a significant difference was seen for an improvement in the severity of the disease in favour of the ciclosporin group when compared to the vehicle. Several side-effects were reported, but none were serious. With topical corticosteroids, the main side-effects were oral candida (yeast) infection and pain or discomfort in the upper abdomen. Temporary burning was a common side-effect reported with tacrolimus 0.1% ointment and pimecrolimus 0.1% cream. Overall, there was no overwhelming evidence for the effectiveness of any single treatment, including topical steroids, which are the widely accepted first-line therapy for ELP. This was mainly due to the lack of good-quality, well-conducted trials and small participant numbers. Another Cochrane review has already assessed interventions for lichen planus affecting the mouth.
We searched the medical literature for studies carried out in any setting comparing needles of different characteristics (i.e. different tip designs and sizes) for the prevention of PDPH. The evidence is current to September 2016. We included 70 studies and were able to include information from 66 of those studies (17,067 participants) in the numerical analysis. An additional 18 studies are awaiting classification and 12 are ongoing. We found that the use of needles with a traumatic tip resulted in a higher risk of PDPH when compared to needles with atraumatic tips. When we compared the different studies comparing various sizes of large and small traumatic gauges, we did not find any difference in effects in terms of the risk of PDPH. Finally, when we compared atraumatic needles with a higher gauge to those with a smaller gauge, we observed no significant differences in terms of the development of PDPH in any of the scenarios analysed. We also found no significant differences in the use of traumatic versus atraumatic needles in the development of adverse effects such as paraesthesia, backache and severe PDPH. The studies did not report clearly on aspects of their design related to randomization. (This is a method that uses the play of chance to assign participants to comparison groups in a trial). This made it difficult for us to interpret the risk of bias in the included studies. We therefore considered the quality of the evidence for most of the outcomes assessed in this review to be moderate.
The evidence in this review is current to 22 November 2017. We found eight studies with a total of 485 participants for complete dentures, and one study with 72 participants for removable partial dentures. The participants ranged from 45 to 75 years old, and had been without their teeth for 10 to 35 years. The studies compared different materials used to make the final impression for dentures (alginate, zinc-oxide eugenol, wax, and addtional silicone, polysulfide or polyether) and different techniques for making the final impression (open-mouth versus closed-mouth, single-stage versus two stage-two step), or both. For most comparisons and outcomes, there was no evidence of a clear difference between the techniques or materials compared. Very low quality-evidence from one study (10 participants) suggested that making dentures with an additional silicone elastomer biofunctional prosthetic required fewer adjustments than conventional methods. Low-quality evidence from another study (144 participants) suggested that complete dentures made with silicone elastomer in a two stage–two step final impression, may be better than those made with alginate, in terms of oral health-related quality of life, stability of the denture, and chewing efficiency. With the limited evidence available, we are unable to draw any conclusions about the best impression techniques and materials for complete and partial removable dentures. There is a need for further research in this area. The quality of the evidence base overall is low to very low. Only one or two studies assessed each intervention and comparison, and most of the studies were at high risk of bias. Many of the studies did not measure our key outcomes. For both complete and partial removable dentures, we conclude that we have no reliable findings.
This review draws together up-to-date evidence from 70 studies including a total of 4761 people. There is continued support for the efficacy of individual TFCBT, EMDR, non-TFCBT and group TFCBT in the treatment of chronic PTSD in adults. Other non-trauma-focused psychological therapies did not reduce PTSD symptoms as significantly. There was evidence that individual TFCBT, EMDR and non-TFCBT are equally effective immediately post-treatment in the treatment of PTSD. There was some evidence that TFCBT and EMDR are superior to non-TFCBT between one to four months following treatment, and also that individual TFCBT, EMDR and non-TFCBT are more effective than other therapies. No specific conflicts of interest were identified. Although we included a substantial number of studies in this review, each only included small numbers of people and some were poorly designed. We assessed the overall quality of the studies as very low and so the findings of this review should be interpreted with caution. There is insufficient evidence to show whether or not psychological therapy is harmful.
As of 15 July 2015, we identified three randomized controlled trials. A total of 466 people with RB participated in the three trials. The trials were conducted in Cameroon, Ghana, and Liberia. In the Cameroon and Ghana trials, people with RB took doxycycline or placebo (sugar pills) for four weeks or six weeks. One dose of ivermectin was then given four or six months later. People were then followed for two to three years. In the trial from Liberia, people with RB were divided into two groups. One group was given doxycycline for 6 weeks followed by a single dose of ivermectin. The other group was given ivermectin alone. Both Liberian groups were followed up for six months. Evidence of the effect of adding doxycycline to the usual treatment of ivermectin for people with river blindness is unclear. Only one of the three trials looked at the vision of participants. This trial reported insufficient evidence to show a difference between treatment groups in the proportion of participants with visual improvement six months after the start of the study. Two trials showed reduced bacteria (Wolbachia) and fewer adult worms with combined doxycycline and ivermectin treatment than with ivermectin alone after about two years. However, new worms with the bacteria were found after treatment in one trial. Two trials reported adverse treatment effects in some participants; both reported no differences between treatment groups. One study reported that adverse treatment effects, including itching, fever, headache, body pain, and vertigo, occurred in 12% of study participants. The other study reported that one (1.3%) person had bloody diarrhea after starting treatment with doxycycline plus ivermectin, which stopped when treatment was withdrawn. We judged the overall quality of the evidence as very low because of methodological issues noted in the trials.
We included 23 studies (2344 participants with WAD Grades 1 or 2), nine of which were new for this update. Overall, the methodological quality was poor and the studies included populations and interventions that were too different to pool. Two studies examined treatments for patients with chronic pain (longer than three months), two looked at subacute pain (four to six weeks), two were unclear (but one was probably chronic), and the rest looked at patients with acute symptoms of less than three weeks. In 11 studies, an active treatment approach (treatment strategy including exercises or advice to 'act as usual') was compared to a passive strategy, no treatment or was an additional treatment. Eight studies compared an active intervention with a passive one (the patient received a treatment such as advice to rest and wear a neck collar, an educational video, electrotherapy, manipulation, hot and cold packs, traction, or acupuncture). Eight studies compared an intervention with a placebo or no treatment. In seven studies, two active treatments were compared against each other and in one, a passive intervention was compared to injections. Since we were unable to pool any of the studies, we remain unable to either support or refute the effects of conservative treatments for acute, subacute or chronic whiplash-associated disorders with the current evidence.
In May 2016 we searched medical databases to find randomised controlled trials looking at the use of skin antiseptics in people with CVCs. We included 13 studies in this review, although only 12 studies contributed data for a total of 3446 CVCs. The study participants were mainly adults in intensive care units or other specialist hospital units. We reported our findings in terms of the number of catheters, as some studies did not provide the number of patients assessed, and some patients had more than one CVC.One study was funded by a national research body, five studies were funded in whole or in part by at least a pharmaceutical company, and in the remaining seven studies funding sources were not stated. Three studies examined the effect of cleansing versus no cleansing, and found no clear evidence of differences in blood infections, infections in the catheter and need for antibiotics between patients who received cleansing compared to those who did not. Chlorhexidine solution may reduce blood infections associated with the catheter compared with povidone-iodine solution (reducing the infection rate from 64 cases per 1000 patients with a CVC with povidone iodine to 41 cases of infection per 1000 with chlorhexidine). This translates into the need to treat 44 people to avoid one additional bloodstream infection. Chlorhexidine solution may (compared with povidone iodine solution) also reduce the presence of infectious organisms within the catheter (reduced from 240 infected catheters per 1000 people to 189 infected catheters per 1000 people). It is unclear whether antiseptic skin cleansing influences mortality rates as only one study reported this and although similar death rates were observed with povidone iodine and chlorhexidine, small numbers mean a difference cannot be ruled out. The overall quality of evidence was poor due to flaws in the way the studies were designed, small study sizes, inconsistency of the results between the included studies and the nature of the outcomes reported. These flaws have reduced our confidence in the results of the studies. This means we cannot be certain whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter-related blood stream infection and other harmful effects, such as overall blood infections and mortality compared with no skin cleansing. Cleansing with chlorhexidine solution may be more effective than povidone iodine but the quality of the evidence was very low.
We searched the medical literature up to April 2019 for trials that evaluated the effectiveness and safety of drugs proposed for the management of neurosyphilis in adults. We found only one randomised clinical trial that met our criteria (patients are randomly put into groups to receive different treatments). This trial involved 36 adults with both syphilis and HIV, who were mainly men, with a median age of 34 years. The trial compared two drugs: ceftriaxone (2 g once daily), and penicillin G (4 million units every 4 hours for 10 days). It was funded by a pharmaceutical company. The trial reported serological cure, which is a decrease in the levels of the infection shown by laboratory analysis of fluids in the brain and spinal cord (known as cerebrospinal fluids), and clinical cure, which is the absence of signs or symptoms of neurosyphilis. Only three of 18 participants receiving ceftriaxone and two of 18 participants receiving penicillin G achieved serological cure; and eight of 18 participants receiving ceftriaxone and two of 18 participants receiving penicillin G achieved clinical cure. There was not enough evidence to allow us to state if there is a difference between treatment with ceftriaxone or Penicillin G for neurosyphilis in adults. The outcomes evaluated could change when trials with a better design become available. Additionally, we did not identify any evidence related to the effectiveness and safety of other drugs proposed to manage this condition. The quality of the evidence was very low for the outcomes serological cure and clinical cure due to problems with the trial's design and methods, and because there was only a small number of participants.
This review compares the effects of zotepine to other second generation antipsychotic drugs. Three trials suggest that the efficacy of zotepine may be comparable to risperidone and remoxipride. The evidence base is insufficient to provide firm conclusions as to whether zotepine is as effective or less effective than clozapine. The movement disorders and the cognitive changes appear to be similar to clozapine, risperidone and remoxipride. The need for antiparkinson medication is similar to risperidone and remoxipride, but may be associated with increased need than necessary with clozapine.
We could include 38 trials in the meta-analyses which investigated the efficacy and safety of dopamine agonist treatment compared to placebo or to other treatments for RLS. The studies were performed mostly in European and Northern American countries. Treatment durations varied from one week to seven months, but most treatments had durations of one to 12 weeks. Patients suffered from moderate to severe RLS and were treated with the dopamine agonists cabergoline, lisuride, pergolide, pramipexole, ropinirole, rotigotine, and sumanirole. Dopamine agonists lead to a larger improvement on the International RLS Severity Rating Scale (IRLS) compared to placebo. Clinicians rated RLS symptoms as more improved with dopamine agonists compared to placebo (CGI-I). Also periodic limb movements in sleep were significantly reduced by dopamine agonists compared to placebo. Sleep efficiency was also slightly improved. Patients rated their quality of sleep and quality of life as markedly improved. Patients were, however, more likely to discontinue dopamine agonist treatment and experienced more adverse events when treated with dopamine agonists compared to placebo. All dopamine agonists were superior to placebo except sumanirole. Indirect descriptive comparisons revealed the highest efficacy for the ergoline dopamine agonists cabergoline and pergolide, which has to be weighed against potentially serious side effects such as cardiac valve fibrosis. The non-ergoline dopamine agonists lisuride, pramipexole, rotigotine, and ropinirole showed adequate efficacy. Augmentation, a serious adverse event in dopaminergic treatment, has not been sufficiently assessed. Future studies need to investigate long-term efficacy of dopamine agonists against placebo or other active treatment and the frequency and the impact of augmentation on treatment outcome during dopaminergic treatment.
Due to its rarity, this review is based on only one very small RCT and one small retrospective study. The data from these studies were too sparse to adequately assess the effectiveness and safety of chemotherapy after surgery (adjuvant chemotherapy) in the treatment of malignant germ cell ovarian cancer. All comparisons were restricted to single study analyses and this review was only based on 32 women, so it was not adequately powered to detect differences in survival. Adverse effects of treatment and recurrence-free survival were incompletely documented and QoL was not reported in any of the studies. We did not find any studies that reported specifically on adults as this disease usually afflicts younger people as opposed to the older population, so there were problems in separating data on adults and children in many of the studies. Many of the treatments used were taken from experiences of treating patients with testicular cancer, as they look similar under the microscope and behave similar clinically. Due to the small number of patients with malignant germ cell cancer in the two studies, our review shows that there were no good quality studies assessing the role of chemotherapy in this disease, be it in early or late stages. There was insufficient evidence to conclude that any form of chemotherapy or best supportive care is superior over the other. This review highlights the need for future good quality, well designed studies.
A detailed and systematic review of the literature revealed that there were six randomised clinical trials including 560 patients. One trial involving 129 patients did not state the number of patients randomised to the two groups. Of the remaining 431 patients in the remaining five trials, 212 patients underwent laparoscopic cholecystectomy with the help of robot assistant and 219 patients underwent the same procedure with the help of a human assistant. All the trials were at high risk of bias (that is, they were prone to systematic underestimation of harms or overestimation of the benefits of the robotic assistant group or the human assistant group because of the beliefs of the people conducting the trial) and errors due to play of chance. Mortality and surgical complications were reported in only one trial with 40 patients. There were no mortality or surgical complications in either group in this trial. Mortality and morbidity were not reported in the remaining trials. Quality of life or the proportion of patients who were discharged as day-patient laparoscopic cholecystectomy patients were not reported in any trial. There was no significant difference in the proportion of patients who underwent conversion to open cholecystectomy or in the operating time between the two groups. In one trial, about one sixth of the laparoscopic cholecystectomies in which a robot assistant was used required temporary use of a human assistant. In another trial, there was no requirement for human assistants. One trial did not report this information. It appears that there was little or no requirement for human assistants in the other three trials. Robot-assisted laparoscopic cholecystectomy does not seem to offer any significant advantages over human-assisted laparoscopic cholecystectomy. However, our present evidence base is limited by trials that all have high risk of systematic errors (potential to underestimate harms or overestimate benefits of the robot assistant group or the human assistant group) and random errors (that is, play of chance). Therefore, further well-designed randomised trials with low risk of systematic errors and low risk of random errors are needed.
The evidence in this review is current up to January 2014. We included 12 studies, which included a total of 578 participants. Ten studies involved a total of 448 children and two involved a total of 130 adolescents and adults. Five studies did laboratory tests to confirm the presence of whooping cough in all participants who took part. Nine studies compared the medicine to a placebo (i.e. a 'dummy' medicine which did not contain the active ingredient being studied) and three studies compared the medicine to no treatment. Seven studies involved hospital inpatients. Three studies reported their start and finish dates; one study recruited participants over 14 months, another over 18 months and another over 31 months. Six studies including 196 participants reported their results in enough detail for us to assess them. Based on these results, antihistamines (one study, 49 participants), pertussis immunoglobulin (one study, 24 participants) and salbutamol (two studies, 42 participants) did not reduce the number of coughing bouts in patients with whooping cough. Neither pertussis immunoglobulin (one study, 46 participants) nor steroids (one study, 11 participants) decreased the length of time participants spent in hospital. One study reported similar rates of side effects in participants treated with pertussis immunoglobulin (4%; rash) or placebo (5%; loose stools, pain and swelling of the skin around where the injection was given). Studies of antihistamines, salbutamol and steroids did not report any results on side effects. None of these six studies reported any results on vomiting, cyanosis, serious complications, death or admission to hospital. Overall, the quality of evidence was low and many of the studies were conducted some years ago. Only three trials reported adequate details of how the type of treatment given was properly concealed from both participants and healthcare professionals. Methods of recording numbers of coughing bouts and whoops also differed between studies. Estimates of the effects of the different treatments were imprecise due to the small numbers of participants from whom results were available. Additionally, these results may not be generalisable to adults or community settings, since most studies involved children and were done in hospital inpatient settings.
We searched 10 databases for studies where ESAs were used to treat critically-ill people. The evidence is current to February 2017. We found 53 studies, involving 945,240 participants treated with epoetin-alfa, epoetin-beta, and darbepoetin-alfa or placebo. Five studies are awaiting classification. Based on mainly low-quality evidence, we were unable to exclude relevant harms in terms of adverse effects of ESAs. 'Adverse effects' included any adverse events and problems from blood clotting in the veins. However, we found low-quality evidence for protective effects on the overall risk of dying in critically-ill people.
The evidence on which this review is based is up-to-date as of May 2016. We found 14 randomised controlled trials (RCTs) of medical and complementary treatments, which involved 909 participants in total. Treatments included herbal extracts, anti-inflammatory drugs, vitamin A, beta carotene supplements and others. Surgical treatment has not been compared with placebo or no treatment in an RCT. Cancer development was measured in studies of three treatments: systemic vitamin A, systemic beta carotene and topical bleomycin. None of these treatments showed effectiveness in preventing cancer development, as measured up to two years for vitamin A and beta carotene, and seven years for bleomycin. Some individual studies of vitamin A and beta carotene suggested that these treatments may be effective for improving or healing oral lesions. However, some studies observed a high rate of relapse in participants whose lesions were initially resolved by treatment. Most treatments caused side effects of differing severity in a high proportion of participants. It seems likely that interventions were well accepted by participants because drop-out rates were similar between treatment and control groups. The available evidence is very limited. Most interventions were assessed by only one small study. Most studies had problems in the way they were conducted, making their results unreliable. We judged the quality of evidence for the outcome of cancer development to be very low. Larger, better studies of longer duration are required. As well as further studies of drug treatment and alternative treatments like vitamins, studies are needed to evaluate the effectiveness and safety of surgery, and of stopping risk factor habits such as smoking.
we looked at adults with anaemia who were due to have an operation, who received iron treatment or usual care, or a 'pretend' iron treatment (placebo) prior to their surgery. We also compared different forms of iron therapy with each other. We included six studies and a total of 372 participants. iron treatment did not reduce the risk of blood transfusion. There is currently insufficient evidence to say whether iron therapy given before surgery prevents transfusions. To date, too few studies involving too small a number of people have been undertaken, and it is not yet possible to obtain a reliable result for the effects of this treatment. the major limitation in study design for all trials was the small size of the sample groups. More research in larger, well-designed trials is needed before a definitive answer can be given about whether iron therapy before surgery is helpful. The Cochrane Review authors judged that five of the six studies included in this review were at a low risk of bias (and so their results are likely to be reliable). This was despite a lack of blinding of participants in five of the trials (which would usually decrease the reliability of the evidence), as the measurement used to assess how well the therapy had worked (blood haemoglobin level) was unlikely to be influenced by the participant or investigator knowing which treatment had been received. The results of one study are at a high risk of bias because participants who did not take 80% of their assigned treatment were not included in the analysis. Overall the quality of evidence is low (according to the GRADE criteria). When additional research becomes available in the future, it is likely to change the results obtained in this review.
The evidence included in this review is current to July 2015. We included eight studies involving 646 participants. All studies evaluated reproductive-aged women who were undertaking diagnostic surgery to investigate symptoms of endometriosis or for other indications. Five studies evaluated the diagnostic accuracy of four urinary biomarkers, including four biomarkers that were expressed differently in women with and without endometriosis and one showing no difference between the two groups. Three other studies just identified three biomarkers that did not distinguish the two groups. None of the assessed biomarkers, including cytokeratin 19 (CK 19), enolase 1 (NNE), vitamin D binding protein (VDBP) and urinary peptide profiling have been evaluated by enough studies to provide a meaningful assessment of test accuracy. None of the tests were accurate enough to replace diagnostic surgery. Several studies identified biomarkers that might be of value in diagnosing endometriosis, but there are too few reports to be sure of their diagnostic benefit. There is not enough evidence to recommend any urinary biomarker for use in clinical practice for the diagnosis of endometriosis. Generally, the reports were of low methodological quality and urine tests were only assessed in small individual studies. More high quality research trials are needed to accurately assess the diagnostic potential of urinary biomarkers identified in small numbers of studies as having value in detecting endometriosis.
Our review pooled findings from 1,198 people with blood pressure over 140/85 mmHg who were enrolled in 25 randomised controlled trials. These trials compared the effect of relaxation either with no treatment or with a dummy treatment which wasn't expected to reduce blood pressure. Overall, relaxation reduced blood pressure by a small amount: the average reduction was 5/3 mmHg, but might be anywhere between 8/5 mmHg and 3/2 mmHg. Different trials gave different − sometimes inconsistent − results. Many of the trials were not well designed or conducted. In the good quality trials, relaxation resulted in smaller average reductions in blood pressure and the results could even be consistent with an average increase in blood pressure. Even when all the trials were put together, the combined group of all the people in all the trials wasn't large enough and the trials didn't run for long enough to tell us whether relaxation could reduce the risk of death, heart attack or stroke. Few people reported side-effects of relaxation and, on average, people were just as likely to report side-effects of the comparison treatment. Different types of relaxation were taught in different trials. It was difficult to disentangle their effects, especially as many trials used a combination of methods. Overall, we found no evidence that autogenic training was effective. Progressive muscle relaxation, cognitive/behavioural therapies and biofeedback seemed to be more likely to reduce blood pressure. However, some of the reduction in blood pressure was almost certainly due to aspects of treatment that were not related to relaxation, such as frequent contact with professionals who were trying to help.
In our search updated in November 2013 we found no randomised studies of droperidol for the treatment of nausea or vomiting for people receiving palliative care or suffering from an incurable progressive medical condition. Several studies reported on the use of droperidol for the prevention of nausea and vomiting associated with chemotherapy. Further studies are needed to find out which medications are most suitable to treat nausea and vomiting in palliative care.
An early surfactant therapy strategy results in a greater number of infants receiving surfactant and so more infants being exposed to the potential risks of intubation and surfactant administration. Although no complications of surfactant administration were reported in the studies reviewed, infants treated with an early surfactant therapy strategy tended to have a higher prevalence of patent ductus arteriosus (PDA). Two trials were terminated prior to achieving the targeted enrollment when the need for mechanical ventilation was found to be significantly different between groups at a scheduled interim analysis. Two other trials experienced slow enrollment leading to reduced numbers.
This review included three randomised controlled trials with a total of 228 eyes. The range of myopia of included patients was -6.0 D to -20.0 D with up to 4.0 D of myopic astigmatism. The results of this review showed that the chance of the uncorrected visual acuity being 20/20 or better was not different between the two groups. Phakic IOL surgery was safer than excimer laser surgical correction for moderate to high myopia as it results in significantly less loss of best spectacle corrected visual acuity (BSCVA) at 12 months postoperatively. Phakic IOL surgery appears to result in better contrast sensitivity than excimer laser correction for moderate to high myopia. Phakic IOL surgery also scored more highly on patient satisfaction/preference questionnaires. Neither technique resulted in any complication that caused a loss of final BSCVA. Only studies that fulfilled the proper requirements were selected for inclusion in the analysis. The limitations of the studies that we included were the relatively short follow up period of one year as well as the fact that many of the interventions studied have now been superseded by more technologically advanced alternatives. In the present day the technology available for both excimer laser and phakic IOL surgical correction of high myopia is better than during the period of the included studies. This review showed that phakic IOLs for the treatment of high myopia were safer and preferred by patients when compared with excimer laser. Studies looking at more up to date technology with longer follow to determine long term safety issues are needed.
We systematically retrieved all randomised trials that compared the effect of a higher BP target (upper BP number less than 150 to 160 mmHg) with a conventional lower BP target (upper BP number less than140 mmHg) in people over the age of 65 years. The evidence is current to February 2017. We found three randomised trials (the 'gold standard' of medical evidence) that investigated this question in a total of 8221 older adults (average age 75 years, 59% female). We did not find a difference between the higher BP target and the conventional lower BP target, however an important difference favoring the lower BP target could not be ruled out. We judged the pooled evidence to be of low-quality and not able to adequately answer the question as to which target BP was better. More good-quality trials addressing this question are needed.
In the current systematic review of randomized controlled trials (RCTs) we aimed to evaluate the efficacy and safety of viral vaccines in these patients. The pre-defined primary outcome was incidence of the infection concerned. Secondary outcomes were mortality due to the viral infection, all-cause mortality, incidence of complications, incidence of severe viral infection, hospitalization rate, in vitro immune response and frequency of adverse effects. Eight RCTs were included. They evaluated heat-inactivated varicella zoster virus (VZV) vaccine (two trials), influenza vaccines (five trials) and inactivated poliovirus vaccine (one trial). There were no RCTs on other viral vaccines (hepatitis A, hepatitis B, measles, mumps, rubella). Only the two trials on VZV vaccine reported our pre-defined primary outcome. All trials reported some of the pre-defined secondary outcomes. We found that inactivated VZV vaccine might reduce the severity of herpes zoster when given before and after stem cell transplant in adults with lymphoma or leukemia. Inactivated influenza vaccine might reduce upper and lower respiratory infections and hospitalization in adults with multiple myeloma who are undergoing chemotherapy, or children with leukemia or lymphoma within two years post-chemotherapy. However, the quality of evidence is not high. Local adverse effects occur frequently with the vaccines, although serious adverse effects appear uncommon. Further high-quality RCTs are needed to clarify the benefits and optimal regimens of viral vaccines for patients with blood cancers.
It was compared with standard treatment in five trials for infants with very severe lung disease and resulted in a reduction in mortality. This effect was observed principally in infants with birth weights over two kilograms. Mechanical ventilation has become standard therapy for severe respiratory failure. There have been no trials in modern neonatal intensive care units so the magnitude of the benefits and harms in current practice are not known.
We found three trials with a total of 204 participants that looked at one SGA (fluoxetine) compared with placebo or light therapy. We did not find any trials on other SGAs. One trial (68 participants) compared fluoxetine with placebo. Fluoxetine appears to work better than placebo for winter depression, but we cannot say this with certainty due to the small numbers involved in the trial. Approximately the same number of participants in both groups experienced a side effect. We found two trials (with 136 participants in total) that compared fluoxetine with light therapy. When we combined the results of these two trials we found that there was no difference between the two groups: approximately 66 people out of 100 improved in both the fluoxetine and light therapy groups. We are unsure whether this summary result is correct because the trials are small and have some problems with their design as well as a high drop-out rate (many participants did not finish the trials). About the same number of participants had side effects in the fluoxetine and light therapy groups. We found three additional studies that gave us information on the side effects of other SGAs (fluoxetine, escitalopram, duloxetine, and reboxetine), but we cannot compare the drugs directly. We can say that about 15% to 27% of people had to leave the studies early because of side effects and that the most common side effects were nausea, diarrhoea, disturbed sleep, decreased sex drive, dry mouth and agitation. We could not compare the rates of side effects in people taking SGAs compared with placebo drugs which means that our confidence in the information on side effects is limited.
The review included nine trials with 645 participants. Six trials assessed TACE versus control and three trials assessed TAE versus control. All trials had risks of systematic errors ('bias'). Contrary to current practice in many hospitals, we could not demonstrate any beneficial effect of TACE or TAE on either survival or tumour growth in patients with primary liver cancer not suitable for surgical resection. Furthermore, we calculated that more clinical trials involving a further 383 trial participants may be needed before firm evidence may become available. Importantly, TACE or TAE is associated with a wide range of adverse events, some being potentially serious. Accordingly, we recommend that TACE or TAE should not be used as standard treatment for liver cancer until firmer evidence is available from randomised clinical trials.
We included 25 trials in the review. Fourteen trials used family-based therapy, one used systems family therapy, one used structural family therapy and seven studies used therapy with family involvement but did not provide specific details about the theory behind the therapy or its procedures, termed other family therapy. Two studies included two family therapy arms each: one included family-based therapy and systems family therapy arms, and one included systems family therapy and other family therapy arms. Four studies compared family therapy approaches to treatment as usual, six compared family therapy approaches to other psychological interventions and two compared family therapy to educational interventions. Twelve studies compared various forms of family therapy approaches to each other. Two studies included both a treatment as usual as well as other psychological intervention arms. Overall there was some low-quality evidence from only two trials to suggest that family therapy approaches may be better than treatment as usual in the short term. The size and very low quality of the evidence base and the consistency of the trial outcomes are insufficient at this time to draw conclusions about whether family therapy approaches offer any clear advantage over educational or psychological interventions. We found very few differences between treatment groups on measures of weight, eating disorder symptoms and family functioning, and these differences were generally not maintained at follow-up. The reporting of death rates was not clear enough to assess whether death is reduced for those treated with family therapy approaches compared to other interventions. There was very little information about the effects of the interventions on general or family functioning. The way the trials were run was not adequately described in many studies and we found potential risks of bias in most of the studies. This limited the meaningful conclusions that we could draw from the studies. Overall, there is a very limited evidence base in this field. There is some low-quality evidence to suggest that family therapy approaches may be effective compared to treatment as usual in the short term. There is insufficient evidence to be able to determine whether family therapy approaches offer any advantage over educational interventions, other types of psychological therapy, or whether one type of family therapy approach is more effective than another. Most of the studies contributing to the findings were undertaken in adolescents and young adults. There are clear implications about how family therapy approaches might be delivered to different age groups, and we need further research to understand what the resulting effects on treatment might be.
Despite a comprehensive search, we identified only three small randomised controlled trials with a total of 109 participants. Each trial tested different interventions for treating a complete intra-articular fracture in which the joint surface is separated from the shaft of the humerus. One trial compared open reduction and internal fixation versus total elbow replacement in people aged 65 years and older. This found some limited evidence that internal fixation is sometimes not practical for some more complex and difficult fractures and that people treated total elbow replacement may have a better outcome early on (around six months). The second trial compared two ways of placing two plates used for internal fixation. These were either perpendicular (where the plates were at right angles to each other along the bone) or parallel (where the plates were on either side of the bone). The trial did not find any major differences in outcome between the two methods. The third trial did not provide clear evidence of a difference in two surgical approaches of managing pre-operative ulnar nerve dysfunction. In all, none of these three under-sized trials provided adequate evidence to determine which of the surgical interventions under test was the most appropriate. The review found no evidence to inform on the use of more current methods of surgical fixation, specifically the use of locking plates.
This review includes 39 randomized trials with a total of 9955 participants. Thirty-one studies (8672 participants) assessed the effectiveness of probiotics for preventing CDAD among participants taking antibiotics. Our results suggest that when probiotics are given with antibiotics the risk of developing CDAD is reduced by 60% on average. Among trials enrolling participants at high risk of developing CDAD (> 5%), the potential benefit of probiotics is more pronounced with a 70% risk reduction on average. Side effects were assessed in 32 studies (8305 participants) and our results suggest that taking probiotics does not increase the risk of developing side effects. The most common side effects reported in these studies include abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. The short-term use of probiotics appears to be safe and effective when used along with antibiotics in patients who are not immunocompromised or severely debilitated. Despite the need for further research, hospitalized patients, particularly those at high risk of CDAD, should be informed of the potential benefits and harms of probiotics.
We searched for studies comparing CPB with standard analgesic therapy in patients with inoperable pancreatic cancer. We were interested in the primary outcome of pain, measured on a visual analogue scale (VAS). We also looked at the amount of opioid (morphine-like drugs) patients took (opioid consumption) and adverse effects of the treatment. Six studies (358 participants) comparing CPB with standard therapy (painkillers) met our inclusion criteria. At four weeks pain scores were significantly lower in the CPB group. Opioid consumption was also significantly lower than in the control group. The main adverse effects were diarrhoea or constipation (this symptom was significantly more likely in the control group, where opioid consumption was higher). Endoscopic ultrasonography (EUS)-guided CPB is becoming popular as a minimally invasive technique that has fewer risks, but we were not able to find any RCTs assessing this method (current medical literature on this subject is limited to studies without control groups). Although the data on EUS-guided CPB and pain control are promising, we await rigorously designed RCTs that may validate these findings. We conclude that, although statistical evidence is minimal for the superiority of pain relief over analgesic therapy, the fact that CPB causes fewer adverse effects than opioids is important for patients.
A literature search up to July 2014 found five trials (involving 4023 women with a median follow-up variable from 16 to 120 months). Since the previous version of this Cochrane review in 2004, one new study has been published. This review of trials found that follow-up programs based on a regular physical examination and a yearly mammogram appear to be as effective as the more intensive approaches and to have similar impact on HRQoL. No significant differences were found between follow-up performed by specialists or family physicians, regularly or on demand. These results should be interpreted with caution bearing in mind that these studies were conducted almost two decades ago; additional trials incorporating new biological knowledge and improved imaging technologies are needed. Allocation concealment was adequate in all but one trial; two trials were judged to be at low risk of selection bias;the blinding of the outcome assessor was not described in two trials. For one trial it was not possible to judge risk of bias because it reported no methodological information.
Cochrane researchers examined the available evidence up to the 2 September 2016. We included three trials with 328 participants that compared six-month ATT with nine-month ATT; two were from India and one was from South Korea. The trials were mostly of high quality, although two had concerns of risk of bias for detecting relapse of the disease. All the trials included HIV-negative adults with TB of the gut (gastrointestinal TB), and one also included TB of the peritoneum (peritoneal TB). The results show that relapse was an uncommon event, but we are uncertain whether or not there is a difference between the six-month and nine-month groups as numbers of participants are small (very low quality evidence). Six-month and nine-month regimens are probably similarly effective in terms of the chances of achieving cure (moderate quality evidence). Death was uncommon in both groups, and all deaths occurred during the first four months of ATT, which suggests that duration of treatment did not have an effect on risk of death. Few people had poor treatment compliance, and few participants experienced side effects that led to their treatment being stopped or changed, and it was not possible to detect a difference between the groups. Six-month regimens are probably as good as nine-month regimens in terms of numbers of people cured. We found no evidence to suggest that six-month regimens are less safe for gastrointestinal and peritoneal TB than nine-month regimens, but we still do not know whether there is a difference in risk of relapse between the two regimens. Further studies are needed to increase our confidence as to whether six-month regimens are as good as nine-month regimens for preventing relapse; and to provide information about treating abdominal TB in children and in people with HIV.
Many of the 39 studies assessed in this review enrolled only a small number of patients and date back to before 1990. The novel drug alvimopan shortened bowel recovery, but many studies failed to report methodology according to current guidelines. Erythromycin, cholecystokinin, cisapride, dopamine-antagonists, propranolol or vasopressin are not supported due to lack of evidence or absence of effect. Intravenous lidocaine and neostigmine might show to be beneficial, but more evidence is needed.
The evidence on which this review is based is correct as of 17 January 2014. Eighteen trials with 650 participants were included. Four of the trials, with a total of 102 participants, compared implant-supported prostheses using a sinus lift with prostheses on short implants (5 to 8.5 mm long) without sinus lift. The remaining 14 trials with a total of 548 participants compared different sinus lift techniques. There is not enough evidence to show whether sinus lift techniques are more or less successful in reducing the number of failures of dental prostheses (artificial teeth) or dental implants when compared to simply using short implants, up to one year after loading. However, there is limited evidence that there are fewer complications when short implants are used without surgical lifts. Complications include sinusitis, infection and bleeding, and when bone grafts are taken from the patient complications can also include nerve injury, problems with walking and infection. The quality of the evidence for whether or not to use a sinus lift procedure was moderate. The evidence for the 14 comparisons of different sinus lift procedures was based on a maximum of two comparisons for each comparison and was low.
We searched for evidence from randomised controlled trials (RCTs) on 31 October 2016 and included six RCTs (707 women). Three RCTs included women with current gestational diabetes and did not report data separately for the population of women relevant to this review. Therefore we have only included outcome data from three RCTs, involving 241 pregnant women and their infants. The quality of the evidence was assessed as being low or very low and the overall risk of bias of the RCTs was varied. The three RCTs all compared an oral anti-diabetic agent (metformin) with insulin in pregnant women with pre-existing (type 2) diabetes. There was no clear difference in the development of pre-eclampsia (high blood pressure and protein in the urine) for women who received metformin compared with insulin (2 RCTs; 227 women; very low-quality evidence), though women receiving metformin were less likely to have pregnancy-induced high blood pressure in one RCT (206 women; low-quality evidence). Women who received metformin were less likely to have a caesarean section birth (3 RCTs; 241 women; low-quality evidence), though no difference was observed in induction of labour (2 RCTs; 35 women; very low-quality evidence). There was no clear difference between groups of infants born to mothers who received metformin or insulin for being large-for-gestational age (1 RCT; 206 infants; very low-quality evidence), though infants born to mothers who received metformin were less likely to have low blood sugar (hypoglycaemia) (3 RCTs; 241 infants; very low-quality evidence). There were no infant deaths (before birth or shortly afterwards) (2 RCTs; very low-quality evidence). The RCTs did not report on many important short- and long-term outcomes, including perineal trauma and a combined outcome of infant death or morbidity, postnatal depression and weight retention for mothers, and adiposity or disability in childhood or adulthood for infants. There is not enough evidence to guide us on the effects of oral anti-diabetic agents in women with established diabetes, impaired glucose tolerance or previous gestational diabetes who are planning a pregnancy, or pregnant women with pre-existing diabetes. Further large, well-designed, RCTs are required and could assess and report on the outcomes suggested in this review, including both short- and long-term outcomes for mothers and their infants.
The evidence available for most outcomes was either low or very low quality. This means that we are unsure of the reliability of these results. We found no evidence for an important difference between NSAIDs and paracetamol for people with strains, sprains and bruises for pain relief, swelling or return to function at seven days or over. However, there was some evidence that people treated with NSAIDs had slightly more side-effects related to the stomach or intestines. Although there was some evidence to suggest a greater return to function at seven days and fewer side-effects for people with sprains, strains and bruises using an NSAID compared with an opioid, we cannot say if this would apply to drugs that are currently available. This is because most of the evidence came from a study that tested an NSAID that is no longer on the market. We found no evidence for an important difference between NSAIDs and a combination of paracetamol and opioid for people with sprains, strains and bruises regarding pain relief, swelling, return to function at seven days or over, or gut-related side-effects. However, the combination painkiller used in the studies is not now in common use. This means that we cannot be sure that these results would currently apply. We found no studies comparing NSAIDs and complementary and alternative medicines. Also, no studies looked at the risk of re-injury after treatment. This review found low or very low-quality but consistent evidence showing no important difference between NSAIDs and paracetamol, opioids or a combination of paracetamol and opioid in pain or swelling after a soft tissue injury. There is low-quality evidence of more gut-related complications with NSAIDs compared with paracetamol. Although there is either low- or very low-quality evidence of better function and fewer adverse events with NSAIDs compared with opioid-containing analgesics, one study dominated this evidence using a now unavailable NSAID and is therefore of uncertain applicability. Further research is required to determine whether there is any difference in return to function or adverse effects between different types of NSAIDs versus paracetamol.
We searched databases until December 2015 for randomized controlled trials (clinical trials where people are randomly allocated to one of two or more treatment groups) in adults (aged 18 years or over), diagnosed with late-stage stomach cancer. We found 11 trials (4014 participants) that met our selection requirements and randomized people to receive targeted treatment plus chemotherapy or chemotherapy alone. Adding molecular-targeted treatment to chemotherapy may have a small effect on survival and on stopping further development of the disease, compared with chemotherapy alone, but the evidence is of low quality. The treatment may increase the likelihood that tumors get smaller (low-quality evidence), but there is insufficient evidence to know how much of a difference it can make to the person's quality of life (very low-quality evidence). It probably increases the risk of adverse events and serious adverse events (moderate-quality evidence). Currently, the evidence is of low quality for survival outcomes, mainly due to the type of study design, and the inconsistencies between the results of individual studies. We therefore suggest that well-designed clinical trials should be performed, to improve the evidence base.
We found consistently strong evidence that the vaccine is effective in preventing the rarer outcome of invasive pneumococcal disease. Evidence from the included studies indicates vaccination might not afford as much protection in adults with chronic illness as it does for healthy adults. The available evidence does not demonstrate that pneumococcal polysaccharide vaccines prevent pneumonia (of all causes) or mortality in adults. This review did not consider adverse events as it was outside the scope of the study.
We found three randomised controlled studies (clinical studies where people are randomly put into one of two or more treatment groups). The studies randomised 153 participants (74 participants to oral vitamin B12 and 79 participants to intramuscular vitamin B12). Treatment duration and follow-up ranged between three and four months. The mean age of participants ranged from 39 to 72 years. Two studies used 1000 μg/day oral vitamin B12 and showed no relevant difference to intramuscularly applied vitamin B12 with regard to vitamin B12 blood levels. One trial used 2000 μg/day vitamin B12 and showed higher vitamin B12 blood levels in favour of oral vitamin B12. Two studies reported side effects. One study stated that no treatment-related side effects were seen in both the oral and intramuscular vitamin B12 groups. One study reported that 2 of 30 participants in the oral vitamin B12 group left the trial early due to side effects. Orally taken vitamin B12 showed lower treatment-associated costs than intramuscular vitamin B12 in one trial. No study reported on clinical signs and symptoms of vitamin B12 deficiency (e.g. fatigue, depression, neurological complications), health-related quality of life, or acceptability of the treatment scheme. The overall quality of the evidence was low or very low, mainly due to the small number of included studies and the low numbers of participants in these studies.
A search of medical databases up to March 2016 found 21 studies with 2372 people which considered pain, movement or both alongside psychological and social outcomes when people with pain and stiffness in their knee, hip, or both took part in exercise. Participation in exercise programmes probably slightly improves pain, physical function, depression, and ability to connect with others, and little or no difference in anxiety. It may improve belief in one's own abilities, and social function. The studies confirmed that: - people who exercised rated their pain to be 1.2 points lower on a scale of 0 to 20 after about 45 weeks (score: 5.3 with exercise compared with 6.5 with no exercise (control), an improvement of 6%). - physical function improved by about 5% over 41 weeks (exercise group improved by 5.6 points on a scale of 0 to 100 (44.3 with exercise compared with 49.9 with control)). - people's confidence in what they could do increased by 2% after 35 weeks (exercise group improved by 1.1 points on a scale of 17 to 85 (65.4 with exercise compared with 64.3 with control)). - people who exercised were 2% less depressed, or half a point on a scale of 0 to 21, after 35 weeks (3.0 points with exercise compared with 3.5 with control). - exercise made people feel less anxious about themselves by 2%, a 0.4 drop on a 0 to 21 scale, after 24 weeks (5.4 points with exercise compared with 5.8 with control). - exercise resulted in social interaction improving by 7.9 points over 36 weeks on a scale of 0 to 100, giving a change of 8% (81.5 with exercise compared with 73.6 with control). The quality of the evidence was generally moderate, but low for confidence in ability, mental health and social function. This is mainly due to varied measures, making comparison more difficult, and because people taking part knew they were exercising so may have been influenced by expectations of improvement. The studies did not report side effects. Studies lasted for different durations, so we do not know if changes occurred quickly and were maintained, or whether improvements were gradual throughout the studies. Some studies took measurements later after the programme than others. Additionally, 12 studies investigated people's opinions, beliefs and experiences of exercise, and whether exercise changed these. The quality of evidence was high overall. Initially people were confused about the characteristics of their pain, which shaped their feelings, behaviours and decisions about relieving pain. People thought movement and exercise was good for joints, but movement caused pain and they worried this might cause them harm. Lack of information from medical professionals meant people avoided physical activity and exercise for fear of causing damage. Overall, people who had taken part in exercise programmes had positive experiences, helping increase their beliefs that exercise could improve pain, physical and mental health, and general quality of life. Providing reassurance and exercise advice, challenging poor health beliefs, and providing enjoyable exercise programmes may encourage participation and benefit the health of many people.
In this systematic review, we summarise three studies in which oxcarbazepine and carbamazepine treatment were compared directly. We found that both drugs appear to be equally effective and to cause side effects equally often. Significantly fewer patients on carbamazepine developed nausea or vomiting during treatment.
Tradiational therapies for pulmonary arterial hypertension include prostacyclin and its analogues, calcium channel blockers, nitric oxide (NO), and important adjunctive therapies, such as anticoagulants and oxygen. Endothelin receptor antagonists have recently been proposed as an alternative to these traditional therapies. This review includes twelve trials on 1471 participants. Endothelin receptor antagonists can improve exercise capacity, symptoms, and cardiopulmonary haemodynamic variables in people with symptomatic pulmonary arterial hypertension over a period of three to six months treatment. There is uncertainty as to whether endothelin receptor antagonists reduce mortality in this population. The most severe potential side effect was hepatic toxicity which was not common in these short-term trials.
Study characteristics: We found six studies focused on young children aged one to four years; two of these studies were included in the original review and four were new studies. The two studies included in the original review used a low concentration of sucrose, just 12%, which is not considered sweet enough for the pain reducing effects. Three of the four new studies were small pilot studies, conducted to inform full trials, and only one study of sweet solutions in young children included large numbers of children. When we compared results of all six studies, only two showed that sugar water (sucrose) reduced pain during injections. However, the four studies that showed no effect all included small numbers of children, therefore they were not considered large enough to detect significant differences in pain. Further well conducted trials with large enough numbers of young children are needed to work out if sweet taste effectively reduces their pain and distress during needles. For older school-aged children, there were two studies published by the same author, both of which were included in the original review. Neither study showed that sweet taste helped to reduce pain. As other studies show that strategies such as distraction and topical anaesthetics can effectively reduce needle pain in school-aged children, further studies of sweet taste for pain management in school-aged children are not warranted. Study funding sources: Of the six studies including young children, two did not acknowledge receipt of research funding. For the remaining four: a state-wide nursing fund supported two of the pilot studies, an internal research institute provided support for the remaining pilot study and another study was supported in part by a Maternal and Child Health grant. The two studies including school-aged children, conducted by the same author, were supported by a grant from the Canadian Institutes of Health Research.
Endometriosis is a common condition affecting women of child-bearing age, and is usually due to the presence of endometrial tissue in places other than the uterus. Common symptoms include pain and infertility. GnRHas are a group of drugs often used to treat endometriosis by decreasing hormone levels. This review found evidence to suggest treatment with a GnRHa improved symptom relief compared with no treatment or placebo. There was no evidence of a statistically significant difference when compared with danazol or intra-uterine progestagen. However, there more side effects in the GnRHa group compared with the danazol group. There is not enough evidence to make clear if higher or lower doses of GnRHa are better, or which length of treatment is best.
This review identified five trials involving 924 people, but none were of high quality. The review found no significant differences between rifabutin- and rifampicin-containing treatment in curing tuberculosis and preventing relapse, but higher doses of rifabutin might be associated with more adverse effects and there was no evidence that it could shorten treatment. However, very few people with HIV and tuberculosis, who are most likely to benefit from use of rifabutin due to its lack of interaction with antiretroviral drugs, were included in the trials. Better quality clinical trials are needed to understand the place of rifabutin in the treatment of people with tuberculosis, particularly those who also have HIV.
We found 13 randomised controlled trials (four more than in the previous version), evaluating 2775 couples, that compared regular ICSI with IMSI for assisted reproduction. These studies were funded by fertility centres and universities. Based on the very low-quality evidence that we found, we are uncertain of the benefit of IMSI over ICSI. The chance of having a live birth with IMSI was between 20% and 32%, compared to 25% with ICSI. For women with a 7% risk of miscarriage with regular ICSI, the risk with IMSI was between 5% and 10%. The clinical pregnancy rate with IMSI was between 35% and 44%, compared with 32% with ICSI. We downgraded the quality of the evidence because of limitations in the included studies (risk of bias), inconsistency of the observed effect across studies, and high risk of publication bias. There was no evidence concerning congenital abnormalities. We conclude that the current evidence is very limited for suggesting using IMSI instead of ICSI in clinical practice.
This review assessed the long-term benefits and risks of approved anti-obesity drugs in clinical trials of 1 to 4 years duration. Sixteen orlistat (10,631 patients), 10 sibutramine (2623 patients) and four rimonabant (6635 patients) studies were examined. High drop-out rates (30% to 40%) were a limitation of nearly all studies. Compared to placebo, all three drugs reduced weight by around five kg or less and orlistat reduced the number of high-risk patients who developed diabetes. No data to show that any of the three drugs lowers the risk of death or cardiovascular disease were found. The most prominent side effects were gastrointestinal for orlistat, cardiovascular for sibutramine (raised blood pressure and/or pulse rate) and psychiatric for rimonabant (mood disorders). In Europe, rimonabant is contraindicated for patients with severe depression and/or patients who are treated with antidepressive medications. Rimonabant is furthermore not recommended for patients with other untreated psychiatric conditions.  We conclude that: 1. average weight losses with current anti-obesity agents appear modest but may be of clinical benefit, and 2. better studies designed to examine mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.
In March 2015 we performed searches to look for new studies in adults with neuropathic pain of at least moderate intensity. We found only two additional small studies that did not provide any good quality evidence for either benefit or harm. This is disappointing, but we can still make useful comments about the drug. Amitriptyline probably does not work in neuropathic pain associated with human immunodeficiency virus (HIV) or treatments for cancer. Amitriptyline probably does work in other types of neuropathic pain, though we cannot be certain of this. Our best guess is that amitriptyline provides pain relief in about 1 in 4 (25%) more people than does placebo, and about 1 in 4 (25%) more people than placebo report having at least one adverse event, which may be troublesome, but probably not serious. We cannot trust either figure based on the information available. The most important message is that amitriptyline probably does give really good pain relief to some people with neuropathic pain, but only a minority of them; amitriptyline will not work for most people.
This review comprised 28 studies of 907 participants, with the quality of evidence being generally poor. Performing ACTs during an acute flare-up of COPD reduced the likelihood of needing mechanical assistance to breathe, as well as the length of time for which it was required. Time spent in hospital was slightly reduced, but there was little evidence to suggest any benefit on future flare-ups or health-related quality of life. Performing ACTs during stable COPD did not appear to affect flare-ups or hospitalisations, however it may improve health-related quality of life. Techniques which involve breathing out against a positive expiratory pressure resistance may provide greater benefits than other types of ACTs. The lack of adverse events observed in this review suggests that ACTs are safe for individuals with COPD.
We included eight short-term studies (less than six months) that randomised people with schizophrenia to either receive sessions of yoga or standard care in this review. The yoga programmes described varied from 45 minutes to 1 hour in length, and from 8 sessions to a maximum of 36 sessions. We found these studies by electronic searching of the Cochrane Schizophrenia Group's register in January 2015. All studies continued prescribed antipsychotic treatment for the participants. Some results suggest that yoga may be beneficial for people with schizophrenia. Yoga may be beneficial to mental state, social functioning and quality of life but the available evidence is weak and needs to be treated with a good degree of caution. No adverse effects were found by the one trial that reported this outcome. Several other important outcomes were not addressed by the studies, including changes in cognition, economic considerations, and daily living activities. There was not enough good-quality evidence in this review to claim that yoga should be prescribed as an add-on to standard care for schizophrenia. Evidence was limited and weak. The number of included studies was small, and only short-term follow-up was reported. More, larger, and long-term trials that focus on important outcomes are therefore necessary. Ben Gray, Senior Peer Researcher, McPin Foundation.http://mcpin.org/
We included one study of 70 participants aged 12 to 50 years old with Marfan syndrome, who were assigned to either a beta-blocker called propranolol or no treatment for an average duration of 9.3 years in the control (no treatment) group and 10.7 years in the treatment group. This study was supported by grants from the National Institute of Health, the US Food and Drug Administration, and the National Marfan Foundation. Propranolol compared to no treatment did not reduce mortality or morbidity, including aortic dissection, aortic regurgitation (leaking of the aortic valve causing reverse blood flow into the heart), heart failure (inability to pump enough blood around the body), and heart surgery. However, it reduced the rate of enlargement of the aortic diameter. Harms have not been fully reported in this study. We judged this trial to have high risk of bias and low-quality evidence. This study provides inadequate evidence to inform people with Marfan syndrome, their families and care-providers.
We found 30 randomised controlled trials comparing intravaginal oestrogenic preparations with one another or with placebo in a total of 6235 postmenopausal women undergoing treatment for the symptoms of vaginal atrophy. The evidence is current to April 2016. There was no evidence of a difference in the proportions of women who reported improvement in symptoms of vaginal atrophy between the following treatment comparisons: oestrogen ring and oestrogen cream, oestrogen ring and oestrogen tablets, oestrogen tablets and oestrogen cream, oestrogen cream and isoflavone gel. However, a higher proportion of women reported improvement in symptoms in the following active treatments compared with placebo: oestrogen ring versus placebo, oestrogen tablets versus placebo and oestrogen cream versus placebo. In the case of oestrogen tablets versus placebo and using a random-effect model for analysis of the data because of substantial heterogeneity, there was no longer evidence of a difference in effect on improvement in symptoms. With respect to safety, a higher proportion of women who received oestrogen cream showed evidence of increase in endometrial thickness compared to those who were treated with oestrogen ring, which may have been due to the higher doses of cream used. However, there was no evidence of a difference in the proportions of women with increase in thickness of the lining of the womb between oestrogen tablets and oestrogen cream. The evidence was of low quality for both improvement in symptoms as reported by women and increase in endometrial thickness. The main limitations of the evidence were poor reporting of study methods, and lack of precision (i.e. effect estimates with wide confidence intervals) in the findings for both outcomes.
The effect of hormone treatment on viral myocarditis remains controversial. The review authors conducted a thorough search of the medical literature. Eight randomised trials with 719 patients which met the inclusion criteria compared hormone treatment plus conventional therapy with no hormone. Hormone treatment did not reduce mortality from viral myocarditis. Improvements in heart function were found but the trials were of low quality and small size so this finding must be regarded as uncertain. Further trials comparing hormone treatment in people suffering viral myocarditis with placebo are warranted. There are no conflicts of interest in the review.
The evidence from the trials in the review indicates that, compared with a placebo and ipratropium, tiotropium does reduce exacerbations and related hospitalisations and improves quality of life and symptoms in people with moderately severe COPD, although the evidence with regards to decline in lung function is less clear. Tiotropium caused dry mouth. Compared with other commonly used drugs in COPD, such as long-acting beta agonists (including salmeterol), there is not enough evidence for us to draw reliable conclusions. In order to better understand the effects of this drug we need long-term studies (over several years), studies conducted in mild and severe COPD, and additional studies that measure outcomes in relation to other agents used in the treatment of this condition.
From analysis of 7 studies, which included 392 participants, we found that this treatment reduces the chance of having a serious allergic reaction to an insect sting by 90%, a consistent finding between studies. Venom immunotherapy also significantly improves the quality of life of people who have had a serious allergic reaction to an insect sting by reducing anxiety and possible limitation of activities caused by fear of insects. However, almost 1 in 10 people treated with venom immunotherapy during the trials had an allergic reaction to their treatment. We were unable to find out whether venom immunotherapy prevents fatal allergic reactions to insect stings, because these are so rare. The decision whether to start venom immunotherapy depends on an accurate diagnosis, followed by careful assessment of a person's risk of having another allergic reaction to a sting, the degree to which the insect sting allergy affects their quality of life, and the risk of an allergic reaction to their treatment.
The review of trials found evidence that synthetic surfactant reduced the risk of RDS in babies considered at risk. Babies who receive prophylactic synthetic surfactant have a decreased risk of RDS, pneumothorax (air in the lung cavity) and death. However, babies who receive prophylactic synthetic surfactant have an increased risk of developing lung hemorrhage and patent ductus arteriosus, an open vessel that channels blood from the lungs to the body. Although this can lead to potentially life threatening complications, the overall benefits of surfactant treatment outweigh the risks.
We included 19 trials with 2565 people with cystic fibrosis; 15 trials (2447 people) compared dornase alfa to placebo (a dummy treatment with no active medication) or no dornase alfa treatment; two trials (32 people) compared daily dornase to hypertonic saline; one trial (48 people) compared daily dornase alfa with hypertonic saline and alternate day dornase alfa; and one trial (38 people) compared dornase alfa to mannitol and the combination of both drugs. People from all age groups (infants through to adults) took part in the trials which lasted from six days to three years. Dornase alfa compared to placebo or no treatment We found that dornase alfa improves lung function within one month when compared to a placebo or no treatment and this improvement was also seen in longer trials lasting from six months to two years (eight trials; 1708 participants). There were also fewer exacerbations (flare up of lung inflammation) in these longer trials. One trial found that the cost savings from dornase alfa offset 18% to 38% of the medication costs. Dornase alfa - daily versus alternate day One trial (43 children) found no differences between treatment schedules for lung function, quality of life or pulmonary exacerbations. Dornase alfa compared to other medications that improve airway clearance The results from trials comparing dornase alfa to hypertonic saline or mannitol were mixed. One trial (43 children) showed a greater improvement in lung function with dornase alfa compared to hypertonic saline and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol. In one trial (23 participants) quality of life scores were better with dornase alfa alone than with dornase alfa plus mannitol; other drug comparisons found no difference between treatments for quality of life. No trials in any comparison of treatments reported any difference between groups in the number of pulmonary exacerbations. Overall, no serious side effects were reported, with only rash and a change in voice seen more frequently in those people taking dornase alfa. However, it is not definitively clear from the current evidence if dornase alfa is better than other medications such as hypertonic saline or mannitol. The quality of evidence from the trials comparing dornase alfa to placebo or no treatment was moderate to high for lung function results, but only one trial reported any changes in quality of life so the evidence for this outcome is limited. Also, there were few trials comparing different treatment schedules of dornase alfa (e.g. once a day versus twice a day) or comparing dornase alfa to other medications which help with clearing secretions, so current evidence from these trials is limited and of low quality.
We identified 10 relevant studies involving data from 944 adults, all male. Few of these studies provided information about the primary outcome of this review, which was reoffending. This was usually because studies did not collect data for a sufficiently long period outside prison or the treatment setting. Many studies relied on other outcome measures (for example, anger or social skills) chosen by investigators in the hope that they were linked in some way with future offending, although it cannot be stated with certainty that such connections reliably predict reoffending. Five of the trials we found involved 664 men and used primarily cognitive behavioural interventions (CBT). In the largest study, which had the most complex and intense 'package' of treatment both within and outside of prison, there was no difference between the group who had received CBT and those who had not in terms of the risk of reoffending as measured by reconviction for sexual offences. One study, involving 231 men, compared psychodynamic intervention with standard care, which was probation, and suggested that probation was mildly superior in terms of reducing reoffending. Behavioural programmes were looked at in four trials involving 70 men. For two studies, not enough data were reported to assess the effectiveness of treatment. For the remaining two, encouraging results with regards to reconvictions and self-reported urges have to be treated with caution as the studies are relatively old, meaning that many participants would not now seek or be offered treatment, as some of the targeted behaviours have been decriminalised. Data for adverse events, 'sexually anomalous urges' and for secondary outcomes thought to be 'dynamic' risk factors for reoffending, including anger and cognitive distortions, were limited. We concluded that further randomised controlled trials are urgently needed in this area, so that society is not lured into a false sense of security in the belief that once the individual has been treated, then their risk of reoffending is reduced. Currently, the evidence does not support this belief.
This review of 2018 patients, from four trials, found that adding cetuximab (a newly developed agent) to standard treatment, prolonged the survival time of advanced NSCLC patients by about 1.5 months, and deferred the progression of cancer by about 0.5 month. One year after the treatment, 45% of the patients receiving standard treatment plus cetuximab, and 40% of the patients receiving standard treatment alone were still alive. However, the effects of cetuximab on quality of life of patients were uncertain. Seven types of adverse events, mainly involving skin and blood, occurred much more in the patients receiving cetuximab, while other adverse events seemed to occur equally in both groups. The adverse events were reported as generally manageable. No deaths related to cetuximab were reported. In summary, high quality evidence shows that the use of cetuximab combined with standard treatment leads to better survival than standard treatment alone, in improving survival of patients with advanced NSCLC.
In a search updated to January 2017, review authors identified 20 studies for inclusion in the review. Sixteen studies (977 infants) compared two separate groups of infants treated with a volume-targeted mode of ventilation compared with a pressure-limited mode of ventilation. In four studies (84 infants), the infants were treated with both modes of ventilation in a cross-over design (where infants had ventilation with one method and were then swapped over to the second method). Most of the studies were of moderate to low quality and none of them were blinded to those who assessed therapy. The most important results from this review were based on data from eight to 12 studies including 584 to 771 infants. Babies ventilated using volume-targeted modes of ventilation were more likely to survive free of lung damage. They needed ventilator assistance for a shorter duration and were less likely to develop pneumothorax (a condition when air escapes from the lung into the chest). They had more stable carbon dioxide levels in the blood, and had fewer brain ultrasound abnormalities. There was no evidence that volume-targeted modes were more likely to harm the infant than traditional pressure-limited modes. More research is needed to understand whether volume-targeted modes also lead to improvements in the development of movement and intellect. More research is also needed comparing different volume-targeting techniques. Low to moderate quality as none of the studies were blinded and there were issues with study design in some of the studies.
There were no studies in people with rheumatoid arthritis that looked at the effects of weak opioids taken for more than six weeks. There were not enough studies of strong opioids to draw conclusions about their effects in rheumatoid arthritis. What is rheumatoid arthritis and what are opioids? When you have rheumatoid arthritis your immune system, which normally fights infection, attacks the lining of your joints. This makes your joints swollen, stiff and painful. The small joints of your hands and feet are usually affected first. There is no cure for rheumatoid arthritis at present, so the treatments aim to relieve the pain and stiffness and improve your ability to move. Opioids are powerful pain-relieving substances that range in strength from relatively mild, such as codeine, to strong, such as morphine. Some examples of weak opioids are codeine (for example Panadeine Forte®) and tramadol (for example Tramal). Some examples of strong opioids are oxycodone (for example Percocet, Endone), morphine and fentanyl (for example Duragesic). They can be taken in a pill form, as an injection or as a patch placed on the skin. Common opioid side-effects include nausea, constipation and drowsiness. Best estimate of what happens to people with rheumatoid arthritis who take opioids Patient-reported global impression of change -18 more people out of 100 reported a 'good' or 'very good' improvement in the symptoms of their rheumatoid arthritis after treatment with opioids for between one and six weeks (18% absolute improvement) -57 people out of 100 reported a 'good' or 'very good' improvement in symptoms -40 people out of 100 who took a placebo reported a 'good' or 'very good' improvement in symptoms Side-effects -30 more people out of 100 experienced at least one side-effect during treatment with opioids for between one and six weeks (30% absolute difference) -51 people out of 100 had at least one side-effect -21 people out of 100 who took a placebo had at least one side-effect
The evidence is current up to 27 August 2014. We found 32 studies with 2844 participants. Most studies compared ultrasound with electrical nerve stimulators or compared ultrasound combined with nerve stimulators against nerve stimulators alone. We reran the search in May 2015. We will deal with the 11 studies of interest when we next update the review. We combined the results of studies using statistical tests and found that nerve blocks were more likely to be assessed as adequate for surgery and were less likely to need additional anaesthetic when performed using ultrasound guidance or ultrasound guidance combined with other techniques. We also found that there were fewer complications such as 'pins and needles' or accidental punctures of blood vessels. It also took less time to perform the nerve block when ultrasound alone was used. There was variation in the quality of the studies and authors had not always made sufficient attempts to ensure that the outcome assessors were unaware of what technique had been used for the nerve block. Studies had also often not clearly explained how experienced the people giving the nerve block were. This is particularly important, as ultrasound is still a relatively new technique and some anaesthetists may have limited experience. We rated our evidence for whether the nerve blocks were sufficient and adequate for surgery as of moderate quality, but evidence for our other outcomes was either low or very low. Our evidence suggests that ultrasound is superior to other techniques for peripheral nerve blocks. However, we are unable to say whether this result depends on the experience of the practitioner in the technique being used.
We found that a lot of shorter studies had been conducted, but only one study met our criteria for this review. It took place in the UK and included two different types of online cognitive training. The control group participated in an online game that was not expected to have cognitive effects. This training lasted six months, and study authors measured cognition at the end of the training period. Resarchers randomised 6742 people in the study, but the dropout rate was high. We thought this put the results at high risk of bias; therefore we considered the quality of evidence provided by this study to be low, meaning that further research might well lead to different results. This study did not measure overall cognitive functioning - which we were most interested in - but it did measure some subtypes of cognitive function. The cognitive training group did slightly better on a test of reasoning, and the control group did very slightly better on a test of working memory, which is a very short-term type of memory. No evidence suggested that the groups differed in memory measured by a word-learning test. We were not able to tell whether taking part in computerised cognitive training in midlife has any lasting effects on cognitive function. We think this is an important question that should be investigated further in trials that test cognitive training over three months or longer. It will also be important for researchers to try to find the best ways to keep people motivated to persist with training.
We assessed the quality of the evidence for quality of life as very low due to the young age of the participants, Insufficient blinding, small number of participants, and imprecision because of wide range of confidence intervals. The effects of exercise-based CR for people with implantable VADs were not clear. The current evidence is inadequate to assess the benefits and harms of exercise-based CR for people with implantable VADs compared with usual care. The amount of randomised controlled trial evidence was very limited and of very low quality. In addition, the training duration was very short term. High-quality randomised controlled trials are needed to collect data on events (death and rehospitalisation), patient-related outcomes (including quality of life), and cost.
We found four studies with 302 people to include in this review. The studies lasted from 29 days to 13 months. Three of these studies included both men and women aged 12 years and over and one study only included adult men. The studies compare gene therapy to a dummy treatment (placebo) both of which are inhaled as a mist into the lungs. The studies were of different designs and used different agents. This meant we could not combine their results. Three of the studies, including the largest and most recent study, showed an improvement in some measures of lung function in people with CF given gene therapy. We did not find that any more clinically relevant outcomes such as quality of life, treatment burden or flare-up of lung disease had improved with treatment. In one study "influenza-like" symptoms were more common in people who received CFTR gene transfer agents but this was not reported when the agent was used repeatedly in a larger study. In those people who took the gene transfer agents, molecules and salt in their lower airways moved more like they do in healthy people. The limited evidence of benefit does not support this as a routine therapy at present. We recommend that future studies are designed and reported clearly so that their results can be incorporated into a systematic review. The most recent study provided detailed information on how the people were put into different treatment groups completely at random, and so we are satisfied that those taking part in the study had an equal chance of being in either group (CFTR gene transfer agent or placebo) and that no one could work out which group the next person would be put into. The other studies reported that people were put into groups at random but did not specify how, so we cannot be sure that there was an equal chance of them being in either group. We believe that the clinicians running all the studies did not know which treatment the people taking part were receiving and that in three of the studies those taking part did not know either, but we could not be sure whether the people taking part in the latest study knew which treatment they were receiving and what effect this knowledge might have on results. Unfortunately, the studies did not report all their results clearly; sometimes results were not reported in a way that we could use for the review and sometimes they were not reported at all. This reduced the certainty with which we judged the overall results.
This systematic review examined randomised controlled trials comparing two commonly available combinations administered at a fixed dose through a single inhaler, fluticasone/salmeterol and budesonide/formoterol. We included five studies which recruited 5537 people. The trials were generally well designed but only recruited adults and adolescents and not children. Participants were already taking regular inhaled steroids before the studies commenced and had mild or moderate asthma based on tests of their airway. We found that the number of people who required treatment with oral steroids and admission to hospital was similar between the treatments, but due to the statistical uncertainty of this result we could not rule out important differences in favour of either drug combination. Additional trials would enable us to draw more reliable conclusions about how well these drugs work compared with each other. We also looked at serious adverse events. Again, the results did not indicate that one combination was clearly better than the other, but again these results were imprecise so we cannot be certain. However, lung function and rescue medication use were similar between the treatments. We could not assess the relative effects of these drugs on mortality because there were so few deaths which leads to statistical uncertainty; out of the five studies, one person died. Quality of life was measured in different ways in two studies and we could not determine how the treatments compared in this respect. Further studies are needed to strengthen and better explain these findings. In particular studies which assess the effects of these therapies in children and studies which measure quality of life are a priority.
Research has shown that physicians in the community (in doctors' offices and clinics) can be partly to blame for resistant bacteria. Studies have shown that physicians inappropriately prescribe antibiotics for infections caused by viruses (such as the common cold). They also prescribe antibiotics that kill a wide variety of bacteria when an antibiotic that kills specific bacteria should be prescribed. Physicians may also prescribe the wrong dose for the wrong length of time. Inappropriate prescribing is due to many factors including patients who insist on antibiotics, physicians who do not have enough time to explain why antibiotics are not necessary and therefore simply prescribe them to save time, physicians who do not know when to prescribe antibiotics or how to recognise a serious bacterial infection, or physicians who are overly cautious. To improve how physicians prescribe antibiotics in the community, methods have been studied. In this review, 39 studies were analysed to determine what works. Using printed materials to educate physicians about prescribing or to give them feedback about how they prescribed did not improve their prescribing or only improved it by a small amount. Meetings to educate physicians improved their prescribing but lectures did not. It was not clear whether personal visits to the physicians by educators worked or not or whether reminders to physicians worked or not . The use of delayed prescriptions decreased use of antibiotics without increasing the risk of serious illness. A delayed prescription means the physician gives a patient a prescription for an antibiotic a few days after the doctor visit; it is thought that if the infection is not serious it will clear up on its own over that time and the patient does not need the antibiotics. The studies also found that using many methods together, such as the ones above, worked better than using one method alone. Since there are many reasons why physicians in the community prescribe antibiotics inappropriately, one method cannot be recommended. But using many methods to change prescribing may be successful.
This review of available trials showed that adding aldosterone antagonist treatment to standard therapy reduced protein release into the urine and lowered blood pressure but had uncertain effects on kidney function and survival. Treatment also increases the amount of potassium in the blood which may require treatment changes, extra blood tests and is potentially harmful. Whether aldosterone blockers protect kidney function to lower the chances needing dialysis or kidney transplantation or prevent heart disease in people who have CKD is unclear and not answered by existing research.
We assessed the evidence from three studies (specifically, randomised controlled trials) comparing oxcarbazepine with phenytoin. We were able to combine information for 480 people from two of the three trials. For the remaining 37 people from one trial, information was not available to use in this review. The evidence is current to 20 August 2018. Results The review found that people taking oxcarbazepine stop taking treatment because of side effects significantly later than people taking phenytoin. Our results also showed that people with focal onset seizures taking phenytoin may stop taking treatment for any reason earlier than people with focal onset seizures taking oxcarbazepine. The results also suggest that people with focal onset seizures taking oxcarbazepine may experience a repeat seizure later, and achieve freedom from seizures earlier, than people with focal onset seizures taking phenytoin. There was no clear difference between the drugs in terms of withdrawal from the treatment, seizure recurrence and seizure remission for individuals with generalised onset seizures. Quality of the evidence The two studies included in analysis were well designed but no information about seizures was recorded after people stopped taking their trial medication, which may have impacted on the results of the study. Most people (70%) included in the studies within this review had focal onset seizures, so the results are mainly relevant to people with this epilepsy type. Also up to 30% of the people in the trials used in our results may have been wrongly classified as having generalised seizures, which may have impacted on the results. For these reasons, we judged the quality of the evidence provided by this review to be of moderate quality for people with focal onset seizures, and low quality for people with generalised onset seizures. Conclusions For people with focal onset seizures, oxcarbazepine may be a preferable treatment to phenytoin, but more information is needed for people with generalised onset seizures to choose between these medications. We recommend that all future trials comparing these medications, or any other antiepileptic medications, should be designed using high-quality methods. Seizure types of people included in trials should also be classified very carefully.
We did not find any randomised controlled trials (where people taking part in the trial have equal chances of being in the treatment or the control group) comparing hydroxyurea with a placebo (a dummy drug) or usual care. However, we found one randomised controlled trial comparing two different doses of hydroxyurea (10 mg/kg/day versus 20 mg/kg/day given for 24 weeks) and included it in this review. A total of 61 people took part in this trial. The lower dose of hydroxyurea appeared to increase levels of foetal haemoglobin, but the higher dose did not. We found some evidence that the higher dose was harmful, particularly to the bone marrow. The trial did not look at whether blood transfusions could be given less often or whether the effects of the anaemia were reduced. In the short term, the lower dose does not appear to have any side effects. The trial duration was very short and we need to know what might happen if treatment with hydroxyurea is continued for a longer period of time. We graded the quality of the evidence as very low. This was because our key results are based on only one small trial. In addition we can not be sure whether the trial methods were of high quality because the authors have not completely described them.
Although we found five studies which looked at anti-rejection drugs, they included people with a number of chronic conditions and not just cystic fibrosis. The studies we found reported results from all volunteers combined and we were not able to isolate the results that were specific to people with cystic fibrosis. We contacted the researchers who conducted these studies, but they have not yet sent us the specific results we need. If we receive these results, we will include them in the future when we update this systematic review. There is a review of drugs to suppress the immune systems of people who have had lung transplants (not restricted to those with cystic fibrosis) and this only included three studies which the review authors judged to have a high risk of bias. The review did not find that any one drug was better than another for reducing the chances of death or acute rejection; but one drug (tacrolimus) led to a lower risk of long-term rejection and high blood pressure, although there was a higher risk of diabetes. Research is needed on the use of drugs that suppress the immune system in people with cystic fibrosis who have received a lung transplant.
Six randomised controlled trials met our inclusion criteria. We found low-quality evidence that pentoxifylline in combination with antibiotics decreases deaths and duration of hospital stay in newborn sepsis. Pentoxifylline treatment did not affect lung, eye, or brain injury as a result of sepsis (very low-quality evidence). We identified no adverse effects due to pentoxifylline. There were no completed studies looking at pentoxifylline treatment in NEC. We need better-quality evidence on the use of pentoxifylline in the treatment of sepsis or NEC in the newborn.
The objective of this review was to assess whether there is evidence from randomised controlled trials that asthma patients benefit from acupuncture. The studies included in the review were of variable quality and had inconsistent results. Future research should concentrate on establishing whether there is a non-specific component of acupuncture which benefits recipients of treatment. There should be an assessment not merely of placebo treatment, but also of 'no treatment' as well. There is insufficient evidence to make recommendations about the value of acupuncture as a treatment for asthma based on current evidence.
We found nine trials, involving 320 people, which evaluated four SSRIs: fluoxetine, fluvoxamine, fenfluramine and citalopram. Five studies included only children and four studies included only adults. One trial enrolled 149 children, but the other trials were much smaller. We found no trials that evaluated sertraline, paroxetine or escitalopram. There is no evidence to support the use of SSRIs to treat autism in children. There is limited evidence, which is not yet sufficiently robust, to suggest effectiveness of SSRIs in adults with autism. Treatment with an SSRI may cause side effects. Decisions about the use of SSRIs for established clinical indications that may co-occur with autism, such as obsessive-compulsive disorder and depression in adults or children, and anxiety in adults, should be made on a case-by-case basis.
We performed a thorough literature search for studies reporting the accuracy of CRP, procalcitonin, or LDH in identifying pancreatic necrosis. We included studies reported until 20 March 2017. We identified three studies reporting information on 242 people with pancreatitis. The studies included pancreatitis due to all causes. Variations in when the studies carried out the blood tests and what level was considered abnormal meant that we were unable to combine the data to provide the overall results. It was not possible to arrive at any firm conclusions about how accurate the tests are for the following reasons. • The studies included few participants. As a result, there was significant uncertainty in the results. • The studies were of poor methodological quality, which introduced additional uncertainty in the results. • For the results to be trusted, they must be reproduced in another group of participants. Since this was not done, there was uncertainty in the results. All of the studies were of unclear or low methodological quality, which may result in arriving at false conclusions.
This review found six trials that included 1078 women. Using information from the trials, we found that giving chemotherapy before surgery helped women to live longer and also to live longer without cancer. It was not clear whether chemotherapy made radical surgery easier or helped to stop the cancer from coming back. The type of drugs used, and how they were given, did not affect the results. Also, results were similar in women with both early stage and more advanced stages of disease. In one trial, all of the women also had radiotherapy after surgery (post-operative radiotherapy). In the other trials, up to two thirds of women got this post-operative radiotherapy. We are not sure how this extra treatment affects the results. It may also give women more side-effects. Although neoadjuvant chemotherapy seems to help women with cervical cancer live for longer and also to live for longer without disease, the results are based on only a small number of trials. If new drugs or new combinations of drugs show promising results, it may be worth doing more trials with these new treatments of neoadjuvant chemotherapy before surgery.
We conducted a systematic search of the literature on the effects of alcohol and drug screening among occupational drivers for preventing injury. We then appraised the quality of the studies found and assessed their results. We found two time-series studies conducted in the USA. One was conducted in five large transportation companies, and it examined the effects of two interventions of interest: implementation of legislation for mandatory random drug testing and mandatory random and for-cause alcohol testing. The other study was conducted using national injury data. There is limited evidence that in the long term mandatory drug-testing interventions can be more effective than no intervention in reducing injuries in occupational drivers. For mandatory alcohol testing there was evidence of an immediate effect only. Given the widespread practice of alcohol and drug testing and the paucity of evaluation studies found, more evaluation studies are needed. Interrupted time-series is a feasible study design for evaluating interventions that aim at preventing alcohol and drug related injuries. However, time-series studies of higher quality and of long duration are needed to increase the level of evidence. A cluster-randomised trial would be the ideal study design to evaluate the effects of interventions for injury prevention in this occupational setting.
We searched medical literature databases to identify studies which tested how well both decision tools can establish whether children are at risk for CSI after blunt trauma. We performed the search in February 2015. We identified three studies of moderate to good quality. All studies tested the accuracy of the NEXUS criteria, and one of them also tested the accuracy of the Canadian C-spine Rules. Since only one study looked at the accuracy of the Canadian C-spine Rules, there is not enough evidence at the moment to determine whether the Canadian C-spine Rules can be used safely in children. The sensitivity and specificity of the NEXUS criteria varied among the three studies, meaning that there is a chance of false-negative test results when using the NEXUS criteria, and as a result there is a chance of missing cervical spine injury if doctors only rely on the NEXUS criteria. We therefore consider that the NEXUS criteria are at best a guide to clinical assessment, with current evidence not supporting strict or protocolized adoption of the tool into pediatric trauma care. The conclusion of our review is that we need more research to evaluate the accuracy of the NEXUS criteria and the Canadian C-spine rules for routine use in children.
The review included seven trials involving 5390 women. These studies show that women who received active management were slightly less likely to have a caesarean section and were more likely to have shorter labours (less than 12 hours). There was no difference in the number of assisted deliveries, nor was there any difference in complications for mothers or their babies when comparing women in the active management group with those receiving routine care.
The evidence is current to August 2015. The participants were adults or children with a common cold. We excluded studies with participants suffering from hay fever, asthma or eczema. The effect of different antihistamines was compared to placebo. A beneficial effect meant a decrease in the severity or duration of the general feeling of illness and/or of specific symptoms such as stuffy nose, runny nose or sneezing. We also investigated whether side effects were more common with antihistamines than placebo. As the common cold usually resolves in seven to 10 days, most studies were of short duration. Where possible we studied the immediate effect and the effect after six to 10 days. Most studies were of good quality although in some studies information to allow us to assess quality was lacking. We considered five out of 16 adults studies and one out of two paediatric studies to be of excellent quality. All trials outlined the financial support received from pharmaceutical companies in the form of grants, supplying the respective intervention drug or having an author currently employed by a pharmaceutical company. In adults, there is a short-term beneficial effect on severity of overall symptoms on the first or second day of treatment (45% felt better versus 38% with placebo), but there was no difference between antihistamines and placebo in the mid to long term. The effect of sedating antihistamines on rhinorrhoea and sneezing is too small to be relevant to the patient and involves a risk of side effects such as sedation (9% versus 5.2% with placebo). Trials in children were smaller and of lower quality and lacked evidence of effectiveness.
None of the studies reported data on quality of life. Many of the studies did not report information on important outcomes such as how long people will live or remain free of breast cancer. We await the publication of one relevant study involving 112 participants who receive chemotherapy before breast cancer surgery for inclusion in an update of this review. In summary, the results found no sufficient evidence of benefit or harm due to the order in which taxane and anthracycline chemotherapies are given. In most institutions, standard practice would be to deliver anthracycline followed by taxane. Based on this review of the evidence, the currently available data do not support a change in this practice. What was studied in the review? For women with early breast cancer who have a higher risk of cancer returning, combination chemotherapy with anthracycline and taxane is often offered either before or after surgery to reduce the risk of cancer returning and prolong life. Traditionally, anthracyclines are given first followed by taxanes but there is no strong evidence for this order. We compared the possibility of giving taxanes first followed by anthracyclines compared to the standard treatment with anthracycline first. What are the main results of the review? All participants in the studies were women. We found five studies involving 1415 participants in which chemotherapy was given prior to surgery. The taxane medicine used in three of these studies was paclitaxel, while the other two studies used docetaxel. Two studies used a single agent anthracycline (epirubicin), while three studies used a combination of epirubicin, cyclophosphamide and fluorouracil. There were also four studies involving 280 participants that compared the order of giving taxanes and anthracyclines to participants who were receiving chemotherapy after breast cancer surgery. The taxane used in all four studies was docetaxel, while the anthracyclines used were a combination of epirubicin or adriamycin plus either cyclophosphamide or fluorouracil (or both). The main results were that the order in which taxane chemotherapy is given: – probably resulted in little to no difference in survival or risk of cancer coming back for participants who receive chemotherapy before surgery; – probably resulted in little or no difference in the degree by which the tumour may have shrunk in response to chemotherapy for participants who received chemotherapy before surgery; – may have resulted in little or no difference in having side effects for participants receiving chemotherapy before surgery but giving taxanes first reduced the risk of neutropenia (low white blood cell count) in those who received chemotherapy after surgery. The side effects that were examined were neutropenia and neurotoxicity (damage to the nerves); – probably resulted in little to no difference in the proportion of participants receiving chemotherapy after breast cancer surgery experiencing delays in chemotherapy doses. Many studies did not collect or report data on survival, the risk of cancer coming back or overall well-being (quality of life). In some cases, the studies did not report data that could be used in the review and we wait for responses from the investigators who conducted the trials. How up-to-date is this review? The review authors searched for studies that had been published up to February 2018.
We included 12 randomised trials with data for more than 11,000 women. Some trials focused on physical checks of the mother and newborn, while others provided support for breastfeeding, and one included the provision of practical support with housework and childcare. They were carried out in both high-resource countries and low-resource settings where women receiving usual care may not have received additional postnatal care after early hospital discharge. The trials focused on three broad types of comparisons: schedules involving more versus less postnatal home visits (five studies), schedules involving different models of care (three studies), and home versus hospital clinic postnatal check-ups (four studies). In all but two of the included studies postnatal care at home was delivered by healthcare professionals. For most of our outcomes only one or two studies provided data and overall results were inconsistent. There was no evidence that home visits were associated with reduced newborn deaths or serious health problems for the mothers. Women's physical and psychological health were not improved with more intensive schedules of home visits although more individualised care improved women's mental health in one study. Overall, babies were less likely to have emergency medical care if their mothers received more postnatal home visits. More home visits may have encouraged more women to exclusively breastfeed their babies. The different outcomes reported in different studies, how the outcomes were measured, and the considerable variation in the interventions and control conditions across studies were limitations of this review. The studies were of mixed quality as regards risk of bias. More research is needed before any particular schedule of postnatal care can be recommended
In nine clinical trials men were either given a dummy tablet (placebo, inactive drug), an alpha blocker for one to three days (in one study up to a maximum of eight days and in another for 32 days) or no treatment before the catheter was removed. In ideal circumstances, neither patients nor doctors knew which type of tablet was given, to prevent the bias in reporting the results. The results suggested that alpha blocker treatment increased the chances of successful catheter removal and return to urination although the overall scientific evidence available to support this was limited. Four different alpha blockers were tested (alfuzosin, tamsulosin, doxazosin and silodosin). Their results were similar except for doxazosin which did not seem to make a significant difference. Side effects caused by alpha blockers were few and comparable to placebo or no treatment, though this evidence was limited. They included retrograde ejaculation, dizziness, low blood pressure, fainting, sleepiness, feeling unwell and headache. There was some evidence to say that alpha blockers also reduce the risk of suffering another (recurrent) episode of urinary retention after successful catheter removal, though it remains unclear whether they reduce the need for future surgery on the prostate. It is therefore unclear whether, or for how long, alpha blocker treatment should be continued after successful catheter removal and whether the costs of alpha blocker treatment in such situations are justified. Further research is needed to answer these questions.
We searched the related literature and included three randomised controlled trials involving 151 adults with pneumonia aged around 60 years. We did not include patients with pulmonary tuberculosis or cystic fibrosis. We found that NIV can reduce the risk of death in the intensive care unit (ICU) and the need for endotracheal intubation, shorten ICU stay and length of intubation. Some outcomes and complications of oxygen therapy depended upon the delivery system and primary diseases. The most common complications of invasive ventilation are ventilator-associated pneumonia. However, we must be aware that oxygen therapy is just one of the treatments for pneumonia and the other standard treatments used by physicians are of equal importance. The evidence is weak and it is limited by the small number of studies and the small number of study participants.
We included five randomized controlled trials involving 1140 women with urine test results showing asymptomatic bacteriuria. Each of the five studies looked at different antibiotics; thus, we have not pooled the results. Four of the comparisons (fosfomycin versus cefuroxime; pivmecillinam versus ampicillin; cephalexin versus Miraxid® (pivmecillinam 200 mg and pivampicillin 250 mg); and cycloserine versus sulphadimidine) showed no definite advantage of one antibiotic over another for treating infection, side effects, or safety. Ampicillin compared with pivmecillinam resulted in less vomiting and was thus better tolerated by the women in one study. There was however no difference in curing present infection and preventing recurring infection in women who took ampicillin compared with those who took pivmecillinam. In another study comparing a one-day versus a seven-day course of nitrofurantoin, the longer course was better in treating bacteria in urine during pregnancy. Women receiving the shorter course had more persistent infection but no clear difference in symptomatic infection at two weeks, nausea or preterm birth.
This review of 22 randomised clinical trials, with a combined total of 3529 patients, set out to determine if any drug was more effective than another in preventing occlusion or restenosis of the artery after the blood vessels have been surgically widened. For the majority of comparisons, only one study was available. Evidence suggests that some drugs which reduce platelet aggregation, such as higher-dose aspirin, can reduce the rate of reocclusion six months after surgery, but evidence on associated side effects and for longer-term restenosis rates is scarce. There is also some evidence of variation in effect according to different drugs, with reocclusion/restenosis rates lower in people taking cilostazol compared with ticlopidine 12 months after surgery and, in patients with more severe disease, those taking low molecular weight heparin in addition to aspirin compared with aspirin alone. Batroxobin plus aspirin compared with aspirin alone may be an effective treatment in diabetic patients. However, available trials are generally small and of variable quality and side effects of drugs are not consistently addressed. Further good quality, large-scale randomised controlled trials, grouped by severity of disease, are required.
Data from 24 studies, most of high quality, including 6885 participants found that rifampin (also known as rifampicin), ciprofloxacin, ceftriaxone and penicillin are effective agents for eradicating carriage of N meningitidis. However, the use of rifampin may have a disadvantage as development of resistance to the antibiotic has been noted following treatment. Mild adverse events are associated with the different antibiotics used. Disease prevention could not be evaluated directly in this review as only data for eradication of the bacteria were available. Different follow-up periods were reported in the studies. Evidence in this review is current as of June 2013.
In this review, only one study of moderate quality evidence was included. The study reported on 4155 women randomly assigned either to an intervention group (2058 women received infection screening and treatment for bacterial vaginosis, trichomonas vaginalis and candidiasis) or a control group (2097 women received screening, but the results of the screening program were not revealed). The present systematic review found that a simple infection screening and treatment program during routine antenatal care may reduce preterm births and preterm low (below 2500 g) and very low (below 1500 g) birthweight. The simple infection screening reduced preterm births from 5% of women in the control group to 3% in the intervention group. The number of low birthweight preterm infants and very low birthweight preterm infants were significantly lower in the intervention group than in the control group. Moreover, an infection screening and treatment program during routine antenatal care is likely to save over EUR 60,000 for each preterm birth averted.
We found no completed (or ongoing) randomised controlled trials that assessed whether creatine given to the mother at times of known, suspected, or potential fetal compromise during pregnancy helps to protect the baby's brain. Randomised controlled trials are needed to establish whether creatine can protect against brain injury for the baby in the womb. The babies in these trials need to be followed up over a long period so that we can monitor the effects of creatine on their development into childhood and adulthood.
This review identified all randomised or quasi-randomised trials of Ginkgo biloba extract in patients with acute ischaemic stroke. There was no convincing evidence, from trials of sufficient methodological quality, to support the routine use of Ginkgo biloba extract to promote recovery after stroke. High-quality and large-scale randomised controlled trials are needed to test its efficacy.
We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of yoga on adults at high risk of developing CVD. We did not included people who had already had CVD (e.g. heart attacks and strokes). The evidence is current to December 2013. We found 11 trials (800 participants), none of them were large enough or of long enough duration to examine the effects of yoga on decreasing death or non-fatal endpoints.There were variations in the style and duration of yoga and the follow-up of the interventions ranged from three to eight months.The results showed that yoga has favourable effects on diastolic blood pressure, high-density lipoprotein (HDL) cholesterol and triglycerides (a blood lipid), and uncertain effects on low-density lipoprotein (LDL) cholesterol. None of the included trials reported adverse events, the occurrence of type 2 diabetes or costs. Longer-term, high-quality trials are needed in order to determine the effectiveness of yoga for CVD prevention. These results should be considered as exploratory and interpreted with caution. This is because the included studies were of short duration, small and at risk of bias (where there was a risk of arriving at the wrong conclusions because of favouritism by the participants or researchers).
We identified 14 studies that were suitable for analysis with a total of 511 participants; 92 were treated by wide resection compared to 419 by intralesional treatment. Age of the participants varied from 13 to 82 years with a mean age of 48 years. Women outnumbered men in the studies by just over one and a half times, which reflects that LGCS are more common in women. People were followed-up for between 24 to 300 months after surgery. In addition, there were four studies including 270 participants, from which we could not extract the exact data, but were used to confirm the statistical analysis. We found that there was little or no difference in rates of local recurrence between treatment types. In 94% to 96% of the cases, the tumour was successfully removed after a single operation. In the few cases where disease recurred, a second operation was needed. People with LGCS probably have better functionality after less aggressive intralesional treatment, and complication rates were probably lower compare to wide surgical resection. Less than 0.3% of all people with LGCS died due to their disease, irrespective of the surgical technique. Overall certainty of the studies was very low, as all studies only described the results of the treatment in hindsight and none of the studies randomly selected patients between treatment groups.
- There was no difference in the number of people who dropped out of the trial because of side effects (difference of 0%). This could be the result of chance.  Side effects - 15 people out of 100 who used electrostimulation experienced side effects (15%). - 15 people out of 100 who used a fake electrostimulation machine or just took their usual treatments experienced side effects (15%). - There was no difference in the number of people who experience side effects (difference of 0%). This could be the result of chance.
We included 13 studies with a total of 468 participants. Most studies included participants with mild or moderate forms of mountain sickness, and only one study included the severe neurological (disorder of the nervous system) form. Follow-up was usually less than one day. We also identified two ongoing studies. We found studies evaluating the following interventions: simulated descent with a hyperbaric chamber (medical use of oxygen in a special chamber at greater than atmospheric pressure to increase the availability of oxygen in the body); oxygen; medicines: acetazolamide, dexamethasone, ibuprofen, paracetamol, gabapentin, sumatriptan, nitric oxide, and magnesium sulphate. None of the studies reported the effects of these interventions on all-cause mortality. The report of complete relief from acute mountain sickness symptoms, and adverse events was infrequent. Studies related to simulated descent with the use of a hyperbaric chamber did not find additional benefits or harms related to this intervention (3 studies, 124 participants). In addition, studies related to administration of medicines found some benefits in terms of reduction of symptoms with the use of acetazolamide (2 studies, 25 participants), and dexamethasone (1 study, 35 participants), without an increase in side effects. The quality of the evidence we found was low, and thus our certainty in the findings is limited. There was insufficient information on how the studies were conducted, and in some cases there was evidence of tampering at some stages of the trials. Furthermore, the number of persons in each study was very small (< 30 participants), and therefore the results were not clear (imprecise). Some studies were not blinded (that is, participants knew what experimental treatment they were receiving), and this could have affected how the participants evaluated their own symptoms.
This review reports trials comparing fluvoxamine with other antidepressants for treatment of major depression. We found no strong evidence that fluvoxamine was either superior or inferior to any other antidepressants in terms of efficacy and tolerability in the acute phase treatment of depression. However, there is evidence of differing side-effect profiles, especially when comparing gastrointestinal side effects between fluvoxamine and tricyclic antidepressants (TCAs). Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations including these differences in side effect profiles.
From the literature search in September 2014, we included one randomised controlled trial, involving 311 participants, that looked at early or delayed radiotherapy given at the time of disease progression in people with LGG. This study was well-designed and reported useful data on survival, but did not include other clinically important information, such as functional independent survival (functional, or neurological impairment, or both) and quality of life. Therefore, we felt that the trial was of unclear quality. People who received early (soon after surgery) radiotherapy had a longer time until their disease progressed than people who only had radiotherapy once the disease had progressed. However, the people that were initially observed had similar survival to the people who had early radiotherapy. Quality of life measures such as memory, executive function, and cognitive deterioration differences were not evaluated in either group. The findings did not suggest that people who received early radiotherapy lived longer than those had delayed radiotherapy. However, people who had early radiotherapy had better control over their seizures than those who had delayed radiotherapy. The toxic effects of radiotherapy were rated as minimal in both groups using a grading system which measured severity and included skin reactions, ear inflammation, mild headache, nausea, and vomiting. Update searches in November 2019 found no new articles which met the inclusion criteria. No articles were considered eligible for inclusion in this review update. Based on the current evidence, the results should be interpreted with caution. It is unclear whether or not early radiotherapy is better than delayed radiotherapy because survival was the same in both groups. People who had early radiotherapy experienced longer periods of tumour remission compared with patients who had delayed radiotherapy. However, it is unclear if these people suffered increased rates of cognitive impairment, neuroendocrine dysfunction, or radiation necrosis compared with people who had delayed radiotherapy. Toxic effects of radiation were minimal in both groups and there were no cases of second malignancies.
We evaluated 26 studies in 2997 people with COPD. Overall the evidence found was of high to moderate quality. The trials were conducted in 11 different countries. The average age of participants was 68 years, 68% of participants were men and the severity of COPD on average was severe (according to lung function measures). Some of the trials took place in GP clinics and some in hospitals. Overall, the studies were of good to moderate methodological quality. People who participated in an IDM program had better quality of life and improved their exercise tolerance after 12 months. Furthermore, in participants treated with such a program, the number of hospital admissions related to exacerbations decreased and the total number of hospital days was reduced by three days. We found no evidence of an effect on mortality. The results support an IDM program for people with COPD to optimize quality of life and exercise tolerance. This plain language summary is up-to-date as of April 2012.
This review suggested that 54 out of every 100 patients who had chemotherapy after surgery were alive after three years, compared to 45 out of every 100 patients who received only surgery. Although these results are encouraging, there are not enough trials or patients for these results to be completely reliable. More randomised trials are needed. This review should encourage greater participation in ongoing randomised trials.
We searched for evidence from randomised controlled trials in August 2017. We found one multicentre study that was at low risk of bias. The study involved 526 women with healthy twin pregnancies that appeared to be normally formed on ultrasound. The women were randomised to have scans to measure either just the growth of the babies or both growth and blood flow to the babies, at 25, 30 and 35 weeks of pregnancy. Findings were similar with the different tests. The study found that having scans to measure growth alone or growth with blood flow made no clear difference to the number of babies that died in the third trimester, at birth, or in the 28 days following birth. There were also no clear differences in the number of babies who were admitted to special care units or needed help breathing (ventilation). We found no difference in numbers of women who had an elective or emergency caesarean section or who were admitted to hospital during their pregnancy (both high-quality evidence). Having different types of scans made no difference to whether women gave birth early or had to have their labour induced (moderate-quality evidence). No information was available on the diagnosis of significant complications during the pregnancy, early preterm births before 28 week's gestation, or women's level of satisfaction with their care. The study did not group the pregnancies by whether the twins shared the same outermost membrane that surrounds them, or not (their chorionicity). If they do, the two babies also share the same placenta and have an intermingled blood circulation, which increases the possibility of twin-related complications. From this one study, we still do not know if the different scanning tests and how often they are done improves outcomes for women with a twin pregnancy. Future studies could find that there are differences in the number of infant deaths with the different ways of scanning. More research is needed to find out how often scans should be done and how detailed they should be in order to see whether the twins are growing normally and to pick up any problems quickly.
There were 35 trials on 11,867 participants that examined whether these interventions are effective in reducing sexual and injection behaviour associated with greater risk of developing HIV. There are not large differences in effectiveness between multi-session psychosocial interventions and briefer interventions. This suggests brief educational interventions are more likely to be cost-effective and may be more readily implemented in a variety of different contexts.
We included trials that used TNF-α blockers as a treatment for children with KD and measured treatment resistance, cardiovascular events and side effects, such as infusion reactions and infections, or other symptoms. We found five completed studies with a total of 494 participants (most recent search for studies September 2018). Four studies used TNF-α blockers as the additional treatment after IVIG treatment and one used TNF-α blockers as the first treatment for children with KD. Key results The analyses showed that TNF-α blockers might reduce treatment resistance by 14% to 62% (low-certainty evidence) and infusion reactions by 55% to 99% (low-certainty evidence). It was not clear whether or not TNF-α blockers were effective in reducing serious heart diseases such as coronary artery abnormalities. There was also no clear difference in the incidence of infections between children who did or didn't receive TNF-α blockers. Certainty of evidence It is important to note that the certainty of evidence is low because the studies only included a small number of participants. Therefore, a large scale clinical trial is needed.
The 18 randomised controlled trials included in this review tested seven comparisons in a total of 2615 mainly female and older participants. All trials had methodological flaws that may affect the validity of their results and there was a general lack of evidence on long-term effects and functional recovery. Some extramedullary implants appeared to be associated with an increased risk of fixation complications and reoperation. In particular, three trials comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (the 'standard' extramedullary device for these fractures) found an increased risk of fixation failure for fixed nail plates. Less invasive implants, such as the external fixator, which require smaller incisions resulted in less blood loss and often quicker operations than the sliding hip screw. We concluded that the sliding hip screw seems preferable to older types of fixed nail plates given their high rate of implant and fixation failure. However, there was not enough evidence to draw conclusions for other comparisons of extramedullary implants or on the use of external fixators.
The people in these studies ranged in age from 18 to 65 years and had pain ranging in severity from mild to substantial. They usually had about five sessions of MET, or the comparison treatment(s), over a period of about 10 days. The review authors aimed to determine if MET helped to relieve pain or increase a person's ability to do normal activities of daily living, or both. Background Low-back pain (LBP) is a common symptom from adolescence into old age. About 50% of the general population experiences back pain over the course of a year and up to 80% of people report LBP over the course of their lifetimes. The vast majority of people have acute (short-term) back pain and recover within a few weeks, with or without treatment. Longer lasting LBP, subacute (for 6 to 12 weeks) and chronic (> 12 weeks) pain, generally has less favourable outcomes. A small proportion of people with acute LBP go on to have chronic disabling LBP, which can interfere with every aspect of normal living, cause significant pain and suffering, and create huge costs in terms of medical care, work disability, and workers’ compensation claims. There are many therapies claimed to be useful for the treatment of LBP. Most of these treatments have not been well investigated or have been found to have modest effects in terms of pain relief and improving disability. For many people with LBP, however, even modestly effective treatments can help in coping with symptoms and returning to normal living. It is therefore useful to explore the effectiveness of treatments that may assist people with LBP, particularly those treatments such as MET which are non-invasive and are likely to be safe and inexpensive. Study characteristics The Cochrane Collaboration researchers looked for studies (randomised controlled trials) published through to May and June 2014. They included studies where MET was delivered by osteopathic physicians, chiropractors, or physical therapists. Twelve randomised controlled trials were found that included a total of 500 patients. All patients in these studies had 'non-specific LBP', meaning that there was no identifiable cause for their back symptoms. After looking at the evidence, The Cochrane Collaboration review authors included four types of comparison treatments, each divided into acute and chronic pain: •MET plus any intervention versus that same intervention alone; •MET versus no treatment; •MET versus sham MET; •MET versus all other therapies. Key results The review authors could not find adequate evidence to make any definitive judgements about the safety or effectiveness of MET. Studies were generally too small and had a high risk of bias, producing unreliable answers about this therapy. There is a need for larger, high-quality studies to determine the effectiveness and safety of MET. At present there is no convincing evidence that MET is effective as a stand-alone therapy or improves the effectiveness as an accompaniment to other therapies. Quality of the evidence The quality of the evidence was poor. The available studies were small and reported only short term outcomes. Most studies were determined to have a high risk of bias because of the way they were designed and conducted.
This review found that although this treatment was better than placebo, the size of the effect was rather small. When the drug was used in combination with more widely used bronchodilators (beta-agonists such as fenoterol), it did not appear to add much benefit. However, there are concerns about the quality of the studies that have been analysed. It could be that there are some adults with chronic asthma who respond to treatment with anticholinergic drugs, but the review has not been able to identify their common characteristics.
The evidence is current to September 2015. We found 13 studies including 2837 participants with a hearing test after platinum-based therapy for different types of childhood cancers. Participants were treated with cisplatin, carboplatin or both, in varying doses. All studies were very different with regard to definitions of hearing loss, used diagnostic tests, participant characteristics, (prior) anti-cancer treatment, other ototoxic drugs and length of follow-up. The reported frequency of hearing loss varied between 0% and 90.1%; none of the studies provided data on tinnitus (that is, ringing in the ears). Three studies reported a frequency of 0%, but none of these studies provided a definition for hearing loss and there might be substantial or even complete overlap in included participants between these three studies. When only studies that did provide a definition for hearing loss were included, the frequency of hearing loss still varied between 1.7% and 90.1%. Only two studies included people who had not received platinum treatment (called control group). In one study, the frequency of hearing loss was 67.1% in people treated with platinum, while in the control group it was 7.4%. In the other study, the frequency of hearing loss was 20.1% in people treated with platinum and 0.44% in the control group. But due to methodological problems of these studies, it is unclear how reliable these results are. Only two studies evaluated possible risk factors. One study found a higher risk of hearing loss in people treated with cisplatin 400 mg/m2 plus carboplatin 1700 mg/m2 compared to treatment with cisplatin 400 mg/m2 or less, irrespective of the definition of hearing loss. They also found a higher risk of hearing loss in people treated with non-anthracycline aminoglycosides antibiotics (that is, a certain type of antibiotics) as compared to people not treated with these antibiotics, for three out of four definitions of hearing loss. The other study reported that age at treatment (lower risk in older children) and single maximum cisplatin dose (higher risk with an increasing dose) were significant predictors for hearing loss, while gender was not. Based on the currently available evidence, we can only advise that children treated with platinum analogues are screened for ototoxicity in order to make it possible to diagnose hearing loss early and to take appropriate measures. However, we are unable to give recommendations for specific follow-up methods including how often hearing is tested. Counselling regarding the prevention of noise pollution can be considered, like the use of noise-limiting equipment, avoiding careers with excess noise and ototoxic medicines. Before definitive conclusions on how often hearing loss happens (called prevalence) and associated risk factors of platinum-induced ototoxicity can be made, more high-quality research is needed. All studies had problems relating to quality of the evidence.
We searched for all relevant, well-conducted studies conducted up to September 2019. We included two randomized controlled trials (experiments in which participants are randomly allocated to two or more interventions, possibly including a control intervention or no intervention, and the results are compared). One study randomized 64 people with severe acute pancreatitis to receive either CVVH (32 people) or no intervention (32 people). The other study randomized 30 people with severe acute pancreatitis to receive either high-volume (high-speed) CVVH (15 people) or standard CVVH (15 people). There were no in-hospital deaths in either group. We cannot tell from our results whether CVVH has an important effect on death or complications for people with severe acute pancreatitis because the sample size was small. High-volume CVVH may have little to no difference on numbers of in-hospital deaths (20.0% with high-volume CVVH versus 33.3% with standard CVVH). We are uncertain whether high-volume CVVH reduces numbers of adverse events (13.3% in both groups). We cannot tell from our results whether high-volume CVVH is superior, equivalent or inferior to standard CVVH for people with severe acute pancreatitis because the sample size was small and the results were imprecise. Most of the included studies had some limitations in terms of how they were conducted or reported. Overall, the quality of the evidence varied from very low to low.
The authors found five studies involving a total of 3,070 participants. All interventions investigated by the studies were found to increase the use of booster seats, compared to the group receiving no intervention. The distribution of free booster seats combined with education on their use, had a marked beneficial effect, as did incentives (for example, booster seat discount coupons or gift certificates) combined with education. Education-only interventions also produced beneficial outcomes. One of the studies evaluated the effectiveness of the enforcement of a booster seat law, but did not detect an effect on usage. The authors concluded that the current evidence suggests that several types of interventions aimed at increasing the use of booster seats among children aged four to eight years, are effective. However, there is still a need for further high quality trials, especially those conducted outside of the USA and Australia, where current research dominates.
This review looked at drugs for the treatment of faecal incontinence. These included anti-diarrhoea drugs or laxatives to regulate stools, and drugs to try to enhance the tone of muscle around the anus which help to keep it closed. Sixteen small trials were found, including 558 participants. The review of these trials found some evidence that anti-diarrhoea drugs may reduce faecal incontinence for people having liquid stools. However, these drugs were associated with some side effects. There was some evidence that drugs to enhance the tone of the muscle around the anus may help, but more research is needed.
Levetiracetam is one of a type of medicine normally used to treat epilepsy. Some of these medicines are also useful for treating neuropathic pain. We looked for clinical trials in which levetiracetam was used to treat neuropathic pain. We found six studies in 344 adult participants with six different neuropathic pain conditions published up to July 2014. These studies were randomised and double blind, which usually means we can trust them. But all had one or more problems that could make the results look better than found in practice. There was no benefit from levetiracetam in any of the six conditions. More participants experienced adverse events with levetiracetam (67 in 100) than with placebo (54 in 100), and stopped taking levetiracetam because of adverse events (13 in 100) than stopped taking placebo (2 in 100). Adverse events included tiredness, dizziness, headache, constipation, and nausea. There was too little information, which was of inadequate quality, to be sure that levetiracetam works as a pain medicine in any of the neuropathic pain conditions investigated. Other medicines have been shown to be effective in some of these conditions.
Adults (18 years of age and older) undergoing surgical procedures, pregnant women in obstetrical labour and patients receiving postoperative pain relief. The evidence is current to September 2013. We found seven studies with a total of 852 participants. The maximum time that a participant was followed by the doctor was 24 hours after giving birth. The quality of the included studies was considered reasonable. The following results were examined: inability to locate the epidural space; accidental catheter placement (mis-insertion of the catheter); combined spinal epidural failure (cases of failed regional anaesthetic technique, which combines the benefits of spinal and epidural anaesthesia); unblocked segments (patchy block); and pain. We found no convincing evidence that results differed when air or saline was used. Because conducted studies were only reasonably well conducted (results very similar across studies; minor issues with study design; and not enough data), we ranked the overall quality of the evidence as low. The applicability of findings might be compromised, as most of the results described in this review were obtained from parturient patients. Low-quality evidence shows that results do not differ between air and saline in using loss of resistance technique for identification of the epidural space and in reducing complications.
We included randomised controlled trials (RCTs). The search is up to date as of 12 July 2018. We found 11 trials with 818 infants. We considered no trial to be at low risk of bias. Four trials included 329 infants in neonatal intensive care units and used a histamine 2 receptor antagonist for prevention of upper gastrointestinal bleeding. These four trials demonstrated a reduction in the incidence of upper gastrointestinal bleeding with a histamine 2 receptor antagonist, but no change in mortality. Outcomes such as serious gastrointestinal problems (e.g. necrotising enterocolitis) and infections were not reported. Seven trials with 489 infants enrolled sick newborn infants with upper gastrointestinal bleeding and used either a histamine 2 receptor antagonist or a proton pump inhibitor for treatment. Use of a histamine 2 receptor antagonist or proton pump inhibitor in a treatment context was associated with a reduction of both duration of upper gastrointestinal bleeding and continued upper gastrointestinal bleeding; however it did not affect mortality or requirement for blood transfusion. No long-term follow-up was reported. Although there is moderate-quality evidence that use of an inhibitor of gastric acid reduces the incidence and duration of upper gastrointestinal bleeding in newborn infants, there is insufficient safety data in this population. The implication of this is that caution should be applied when deciding whether to use an inhibitor of gastric acid in sick newborn infants until additional studies are performed. We graded the quality of evidence for prevention of upper gastrointestinal bleeding as low and moderate. We graded the quality of evidence for the treatment of upper gastrointestinal bleeding as low and very low.
This review examined clinical trials on psychological treatments and antidepressant drugs in depressed patients with coronary artery disease. The objective was to determine the effects of these treatments on depression, death rates, cardiac events such as another heart attack or surgeries, healthcare costs and quality of life. Sixteen trials were identified as relevant for the review. Seven trials investigated psychological treatments, eight trials antidepressant medications and one trial comprised both psychological and drug treatments. Psychological treatments and antidepressant drugs proved to be slightly superior to usual care or placebo (inactive drug) with regard to depressive symptoms. Furthermore, antidepressant drugs might be superior to placebo in reducing subsequent hospitalization rates and emergency room visits. In contrast, there seems to be no positive effect on death rates and cardiac events. Results regarding quality of life are inconclusive. In summary, psychological treatments and antidepressant medications may have a small yet positive effect on depression outcomes in CAD patients. However, the evidence is sparse due to the low number of trials.
There is no evidence from randomised controlled trials regarding the effects of preconception advice on the chances of a live birth in subfertile people. Infertility is a prevalent problem and has significant consequences for individuals, families and the wider community. People's chance of having a healthy, live birth may be impacted upon by factors such as weight, diet, smoking, other substance abuse, environmental pollutants, infections, medical conditions, medications and family medical history. However, there is no current guideline about what preconception advice should be offered to people presenting for infertility treatment. It is important to determine what preconception advice should be given about these types of factors to people presenting for fertility treatment in order to help them to make positive changes and hopefully improve their chances of conception and having a healthy baby. This review found no evidence from controlled clinical trials about the effect of preconception advice on the chance of a live birth in subfertile people.
The review includes clinical studies where participants were randomly assigned to the intervention or to the comparison group (randomised controlled trials, RCTs). Our review includes 42 RCTs with 7935 women. In all trials the aromatase inhibitor used was letrozole. Comparators included CC, which was used in 25 of the RCTs, and laparoscopic ovarian drilling (a surgical technique to puncture the membrane surrounding the ovary), which was used in five RCTs. Several studies included other treatments in one or both arms. Letrozole appears to improve live birth and pregnancy rates compared to CC when used to cause ovulation and timed intercourse. The quality of this evidence was moderate and seems to be reliable. There appeared to be no difference for miscarriage rate or multiple pregnancy rate. There appeared to be no difference between letrozole and laparoscopic ovarian drilling for any observed outcomes, although there were few relevant studies. Ovarian hyperstimulation syndrome (OHSS), a serious adverse event of hormonal stimulation, was a very rare event and in most studies it did not occur. The evidence is current to January 2018. The overall quality of the evidence ranged from moderate to high. Some studies in favour of clomiphene citrate may never have been published. It appears that studies that reported live births report higher clinical pregnancy rates in the letrozole group than studies that failed to report live births. This suggests that results might be somewhat less favourable to letrozole if all studies reported live births.
Trials of medications used to improve the breastmilk supply in mothers who have insufficient milk for their hospitalised preterm infants' needs have been reported in two randomised controlled studies involving 59 mothers. These two studies gave the women domperidone 10 mg three times a day when mothers had insufficient EBM, two to three weeks after delivery. These studies showed a modest improvement in EBM volume over the following one to two weeks. No side effects to mothers or infants were noted in these studies. These medications should only be considered in mothers who have received full lactation support and are more than 14 days post delivery but have insufficient EBM for their infants' needs.
We conducted a thorough search of electronic databases, trial registers and conference proceedings up to July 2012. We included 11 studies in our analysis. The studies were moderate to good quality. Four studies (277 suspected fractures) looked at CT, five studies (221 suspected fractures) looked at MRI and six studies (543 suspected fractures) looked at BS. Four of these studies directly compared two modalities, such as both CT and MRI. When we compared the pooled data for the different imaging tests from all studies, we found that BS has the highest sensitivity, but specificity was lower than CT and MRI. All three imaging tests were found to be highly accurate for definitive diagnosis. CT and MRI were comparable in diagnostic accuracy (the correct diagnosis is made). Although BS had significantly better accuracy than CT and MRI, it could lead to more people receiving unnecessary treatment. Moreover, BS is an invasive technique and is believed to be inappropriate for use in some populations, especially children. Future studies should focus on improving clinical evaluation to raise the prevalence of true fractures. In addition, more direct comparison studies could add valuable data to determine which modality is superior in diagnosis of suspected scaphoid fractures.
We searched medical databases for clinical trials comparing topical NSAIDs with placebo (creams or gels that do not contain a medicine) or other medicines in adults aged 16 years or older with musculoskeletal pain (typically sports injuries). The evidence is current to February 2015. This review is an update of 'Topical NSAIDs for acute pain in adults' originally published in Issue 6, 2010. We identified 14 new studies to add to the 47 studies included in the earlier review. We also identified 14 studies in a clinical trial registry that are completed and three short reports from meetings, for which we could not find full details (about 4500 participants). Three more studies are ongoing (almost 900 participants). The 61 included studies, involving 8386 participants, were generally of high-quality. They tested a number of different topical drugs, mostly against a topical placebo (carrier without the NSAID), with application at least once a day. We were interested in participants having good pain reduction (by about half) around seven days after treatment started. At later times, most people are expected to get better even without treatment. We looked at particular formulations of individual drugs. Gel formulations of diclofenac and ketoprofen were among the most effective, along with ibuprofen gel and diclofenac plaster. For diclofenac and ketoprofen gels, 7 or 8 people out of 10 with a painful strain, sprain, or muscle pull had much reduced pain after seven days, compared with only 2 or 3 out of 10 with placebo (high quality data). Other NSAIDs and formulations were better than placebo, but not by as much. Because both topical NSAIDs and topical placebo are rubbed into the skin in these studies, we know that any effect is not just from rubbing. About 1 in 20 people experienced a mild and short-lived side effect like redness at the application site. This was the same for topical NSAID and topical placebo (high quality data). Side effects like a stomach upset or feeling sick were uncommon, with no difference between topical NSAID and topical placebo (high quality data). There were no serious side effects.
Two randomised clinical trials on the puncture, aspiration, injection, and re-aspiration method for patients with uncomplicated hepatic hydatid cyst were identified. One trial compared puncture, aspiration, injection, and re-aspiration with surgical treatment. The other trial compared puncture, aspiration, injection, and re-aspiration with or without albendazole with albendazole alone. Both trials had high risk of bias. The number of participants enrolled and the follow-up duration are insufficient for a definite conclusion to be drawn. In general, there is insufficient evidence to support or refute the puncture, aspiration, injection, and re-aspiration method with or without benzimidazole coverage for patients with uncomplicated hepatic hydatid cyst.
Evidence is current to November 2014. We included studies in children (aged older than 28 days and younger than 18 years) and adult patients (aged 18 years or older) of either gender undergoing surgery on digits (fingers and toes) under nerve blocks using adrenaline with lidocaine. We found four eligible studies with 167 participants. One small study reported the duration of anaesthesia and found that adrenaline prolonged the duration of anaesthesia, but the quality of the evidence was low. No study reported on adverse events such as ischaemia distal to the injection site or cost analysis with use of adrenaline with lidocaine. Duration of postoperative pain relief was reported by one study, but available data were insufficient for analysis of the findings. Two studies reported reduced bleeding during surgery with use of adrenaline with lidocaine. In the light of our results, we would expect that 17.2 out of 100 patients who received adrenaline with lidocaine (between 8.7 and 29.8 patients) would have bleeding during surgery compared with 49 patients who would have received plain lidocaine; however, the quality of the evidence was low, and further research is very likely to impact our confidence in this estimate. The quality of evidence is low for both duration of anaesthesia and bleeding during surgery with use of adrenaline with lidocaine. Further research is needed to prove the benefits of adding adrenaline to lidocaine.
Three studies (total participants: 855) fit our inclusion criteria. There were two main comparisons: i) chlorhexidine dressing and alcohol skin cleansing against standard polyurethane dressing and povidone-iodine skin cleansing (from one large study), and ii) silver-alginate patch against a control group without patch (from two smaller studies). The quality of the included studies are high, except that the people closely involved in the trials such as the care personnel were not masked from knowing whether or not the infants in the study were given antiseptic or antibiotic dressing, which might have affected their recording or interpretation of the results. One of the studies was funded in part by Johnson and Johnson Medical; Children's Foundation; Children's Hospital, Milwaukee and National Institutes of Health. Another study was funded by the Vanderbilt NICU Research Fund. Funding source was not stated in the third study. In our main findings, chlorhexidine dressing/alcohol skin cleansing made no difference to catheter-related blood stream infection (CRBSI) and blood stream infection ("sepsis") without an identifiable source, although it significantly reduced the chance of micro-organisms lodging in the CVCs ("catheter colonisation"), with an average of 9% reduction in risk among newborn infants with a baseline risk of 24% (1 study, 655 infants). However, infants who received chlorhexidine dressing/alcohol skin cleansing were more likely to develop skin irritation ("contact dermatitis"), as 19 out of 335 infants (5.7%) in the chlorhexidine group developed this complication compared to none in the group that received standard dressing/povidone-iodine cleansing. However, it was unclear whether the dressing or the alcohol solution was mainly responsible for the skin irritation, as the other group did not use alcohol solution for skin cleansing. In the other comparison, silver-alginate patch made no overall differences in CRBSI and mortality compared to no dressing, neither did it cause any adverse reaction. There was moderate-quality evidence for all the major outcomes. The major factor that affected the quality of evidence was the lack of precision in the result estimates, as the calculated plausible range of the effects (the 95% confidence intervals) were wide. Chlorhexidine CVC dressing with alcohol skin cleansing posed a high risk of skin irritation against a modest reduction in catheter colonisation. For silver-alginate patch, evidence is still insufficient for a clear picture of benefit an harm. We have made recommendations for future research that evaluate these interventions.
These scopes allow the intubator to see the airway via a camera, but no reviews have examined the use of an FIS in this situation. Intubation with an FIS is considered an advanced method, requiring training and experience; therefore it may be underused in clinical practice. We aimed to compare the safety and effectiveness of an FIS used for tracheal intubation in obese patients with direct laryngoscopy and other intubation methods that give the intubator an indirect view of the larynx. These other methods include videolaryngoscopes (VLSs)—metal laryngoscopes that contain a camera. We found three small studies, with a total of 131 patients, that compared an FIS with a VLS. The results for all patient safety outcomes were inconclusive, and no differences were noted between intubation with a flexible scope and intubation with a videolaryngoscope. We are unable to make any recommendations for practice based on this review. More research is needed to identify the technique for intubating obese people that would offer the best success rate with the fewest complications.
We searched for evidence on 15 July 2015 and included four randomised controlled studies with 4608, women but only two of the studies had useable data. We assessed both studies contributing outcome data as being at a high risk of bias. One study compared the effect of the baby suckling immediately after birth with no intervention. Another study compared nipple stimulation (with a breast pump) versus oxytocin injection. Neither study reported postpartum haemorrhage. Side effects of the treatments were not reported. Similarly, there was limited information on other consequences for women and their babies. When comparing nipple stimulation (suckling) with no breastfeeding, there were no clear differences in terms of the number of maternal deaths. The incidence of severe maternal illness was not reported. One woman in the suckling group died as a result of a retained placenta. Blood loss greater than or equal to 500 mL, retained placenta, perinatal deaths and maternal readmission to hospital were not clearly different between those who breast fed and those who did not. While these data were based on a single study with a reasonable sample size (4227 women), the results were mostly of low or very low quality due to concerns related to data analysis and study methodology. Our comparison of nipple stimulation (using a breast pump) versus oxytocin included one small study involving 85 women only. There was no clear difference between the groups in relation to blood loss or postnatal anaemia. These results were of low quality due to our concerns about the way the trial was conducted and its small size. There is insufficient evidence to evaluate the effectiveness of nipple stimulation for reducing bleeding during the third stage of labour and more evidence from high-quality studies is warranted. Future randomised clinical trials, with sufficient sample sizes should assess the impact of nipple stimulation in comparison to agents that stimulate the uterus such as syntometrine or oxytocin alone and report on important outcomes such as those listed in this review.
A single study of 256 women who had experienced GDM whether posting reminder letters to 213 women or their doctors, three months after the birth of a baby, would help to increase the number of women taking a blood glucose test compared with 43 women sent no reminder. This study showed that, compared with no reminder, a postal reminder was around two to four times (depending on the blood glucose test concerned) more likely to encourage women who had experienced GDM to take a blood glucose test three months after having their baby. It did not seem to make a difference if the reminder was sent to the woman only, the physician only or to both the woman and the physician. The trial did not assess women's quality of life, or how many women were subsequently diagnosed with type 2 diabetes or impaired glucose results after giving birth. Other kinds of reminders such as email and telephone need to be assessed in studies as they might be easier and more convenient for women than posted reminders. We need to know more about women's preferences and attitudes, and also to find out whether increasing the chances of a woman being tested helps to reduce her risk of developing type 2 diabetes in the future, for example by encouraging a healthier diet and more exercise. The overall quality of evidence was considered low as the only included study involved few numbers of participants and provided imprecise results. This evidence is up to date as of June 2013.
We looked for studies at least 8 weeks' long that compared a group of people with stable asthma who stopped taking LABA versus a group who continued taking ICS+LABA together. We were mainly interested in determining whether stopping LABA had an effect on asthma attacks, asthma control or side effects. What did we find out? We included in the data analyses five studies of people with stable asthma. We rated the overall quality of evidence as moderate for most outcomes, meaning that additional studies are likely to change our confidence in what we found. It looked as though people who stopped LABA might be more likely to have asthma attacks needing treatment with oral steroids, but this is uncertain. Over 17 weeks, 19 of 1000 people continuing their LABA had an attack, compared with 32 of 1000 who stopped taking LABA. This means that 13 more people in 1000 would have an attack if they stopped their LABA, but the uncertainty meant that between 3 fewer and 46 more could be affected. Asthma control and asthma-related quality of life were a bit worse among people who stopped taking LABA, and we could not tell whether stopping LABA increased serious side effects or admission to the hospital.
This systematic review assesses randomised trials that have addressed the benefits and risks of combined treatment of perianal abscesses and fistulae. Six studies have been published on this topic. The analyses show that combined treatment reduces the risk of persistent abscess or fistula, or repeat surgery without a statistically significant increase in postoperative incontinence.
The evidence was current to 7 April 2014. We included 12 studies involving 9547 COPD patients over a period of four to 52 weeks. These studies were sponsored by drug companies and were well designed. Both patients and the people doing the research did not know which treatment the patients were getting; although in one study one treatment was known to both parties. More men than women took part, and they were mostly Caucasians. They were in their 60s and had smoked a lot in their lives. These people had moderate to severe symptoms when they started treatment. Aclidinium did not reduce the number of people with flare-ups that need additional drugs. There was little or no difference in deaths or serious side effects between aclidinium and a dummy inhaler. Aclidinium inhalers improved quality of life more than the dummy inhalers. People who took aclidinium had fewer hospital admissions due to serious flare-ups. Based on our results, among 1000 COPD patients using a dummy inhaler over four weeks to one year 37 would have severe flare-ups needing hospital admission. Only 17 to 33 patients out of 1000 would require hospital admission if they were using aclidinium inhalers. We also set out to compare this new medication with tiotropium, which is already used to treat COPD. There were only two studies for this comparison thus we could not be sure how aclidinium compared to tiotropium. We also could not compare aclidinium with another well known inhaler that contains the drug formoterol because of unreliable data. For the comparison of aclidinium inhalers and dummy inhalers, we are confident that there are benefits in terms of the number of hospitalisations and patients' quality of life; we are less certain about the numbers of flare-ups needing additional drugs and serious side effects. We do not have enough information to assess any effect on the number of deaths. We did not have enough information to reliably compare aclidinium with tiotropium or formoterol.
This review found 43 RCTs conducted up to July 2013 that included 4,084 participants with hot flushes who were close to the menopause or were menopausal. Evidence obtained is current to July 2013. Some trials reported a slight reduction in hot flushes and night sweats with phytoestrogen-based treatment. Extracts containing high levels of genistein (a substance derived from soy) appeared to reduce the number of daily hot flushes and need to be investigated further. Overall no indication suggested that other types of phytoestrogens work any better than no treatment. No evidence was found of harmful effects on the lining of the womb, stimulation of the vagina or other adverse effects with short-term use. Many of the trials in this review were small, of short duration and of poor quality, and the types of phytoestrogens used varied substantially.
We searched for evidence on 29 February 2016. This updated review now includes 28 randomised controlled studies involving 107,362 women. Twenty studies involving 27,865 women looked at interventions to increase the number of women who started breastfeeding, in three high-income countries (Australia, 1 study; UK, 4 studies; and USA, 14 studies) and one lower middle-income country (Nicaragua, 1 study). Three studies investigated the effect of an intervention to increase the number of women who started breastfeeding early, within one hour after birth. These involved 76,373 women from Malawi, Nigeria and Ghana. The study from Malawi was large, with 55,931 participants. Health education delivered by doctors and nurses and counselling and peer support by trained volunteers improved the number of women who began breastfeeding their babies. Five studies involving 564 women reported that women who received breastfeeding education and support from doctors or nurses were more likely to start breastfeeding compared to women who received standard care. Four of these studies were conducted in low-income or amongst minority ethnic women in the USA, where baseline breastfeeding rates are typically low. Eight studies involving 5712 women showed improved rates of starting breastfeeding with trained volunteer-delivered interventions and support groups compared to the women who received standard care. Breastfeeding education provided by trained volunteers could also improve the rates of early initiation of breastfeeding, within one hour of giving birth, in low-income countries. We assessed all the evidence in this review to be low-quality because of limitations in study design and variations in the interventions, to whom, when, where, and how an intervention was delivered. Standard care also differed and could include some breastfeeding support, for example, in the UK. We found too little evidence to say whether strategies with multimedia, early mother-infant contact, or community-based breastfeeding groups were able to improve breastfeeding initiation. Health professionals with training in breastfeeding including midwives, nurses, and doctors, and trained volunteers can deliver education sessions and provide counselling and peer support to increase the number of women who start breastfeeding their babies. High-quality research is needed to understand which interventions are likely to be effective in different population groups. More studies are needed in low- and middle-income countries to find out which strategies will encourage women to start breastfeeding just after giving birth.
In this review, we have compared stage-based programmes of smoking cessation with standard (unstaged) programmes, or with 'usual care', or with assessment only. We found 41 stage-based trials, covering more than 33,000 smokers, which measured quit rates at least six months after treatment. Only four of the 41 trials directly compared the same intervention in a standard and a stage-based version. This showed that the stage-based version was neither more nor less effective than the standard one. Eighteen trials which compared stage-based self-help programmes with any control condition showed better success rates for the intervention groups. Thirteen trials of stage-based individual counselling versus any control condition showed a similar benefit for the intervention groups. These findings confirm the known effectiveness of these interventions, whether staged or unstaged. The evidence was less clear on the effects of stage-based telephone counselling, interactive computer programmes or training of doctors and helpers. This uncertainty may be due in part to smaller numbers of trials. We find on the evidence from this review that providing self-help or counselling support to smokers trying to quit is more effective than 'usual care' or simple observation. However, the extra value of fitting that support to the smoker's stage of change is currently unclear.
We found 24 studies with a total of 7279 people. Two studies focused on helping those who had recently stopped smoking and the rest of the studies included current smokers who wished to quit. All the studies were conducted with adults. Eleven studies were with women only and one with men only. Most studies recruited fairly inactive people. Most studies offered supervised and group-based, aerobic-type exercise. The evidence is up-to-date to May 2019. When we combined the results of 21 studies (6607 participants) which compared exercise and smoking-cessation programmes to smoking cessation programmes alone, there was no evidence that exercise increased quit rates at six months or longer. There was no evidence that the effect was different for different types of exercise. When we combined results from two studies (453 participants), there was no evidence that exercise helped people who had recently quit to stay quit. We judged the quality of evidence for whether exercise programmes help people quit smoking as low certainty, suggesting that future research could change these results. The low certainty is because we cannot rule out chance as an explanation for the suggested slight benefit. It could be that exercise may not help at all, or it could be that supporting people to do exercise modestly increases quit rates. We do not know which of these is true. We also consider that a good number of the trials may be biased. We have concerns that small studies which found smaller effects were less likely to be published than small studies which found bigger effects, making the average result misleading. We judged the evidence from two studies examining whether exercise helps people to avoid relapse to smoking to be of very low certainty, again suggesting that more research is needed. This is due to imprecision of the estimated effects and a high risk of bias in the methods used by one of the studies.
The reviewers identified 10 trials that compare various fistula treatments against one another. There are various parameters that these procedures can be compared on, but we looked at the two most important ones, recurrence (the numbers who got the disease again) and incontinence (a worsening in the ability to control rectal content). In the trials that were compared, there was no significant difference between the various comparisons for the disease to recur. However the trials on fibrin glue, as well as data from non randomised trials show that incontinence is less, probably as there is no surgical disruption of the anal muscle. There is a paucity of good quality data that compares various types of operative treatment for anorectal fistula and there is scope for further trials in the area.
The evidence included in this review is current to July 2015. We included 141 studies involving 15,141 participants. All studies evaluated reproductive-aged women who were undertaking diagnostic surgery because they were suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). Cancer antigen-125 (CA-125) was the most common blood biomarker studied. Seventy studies evaluated 47 blood biomarkers that were expressed differently in women with and without endometriosis, and 82 studies identified 97 biomarkers that did not distinguish between the two groups. Twenty-two biomarkers were in both categories. Only four of the assessed biomarkers (anti-endometrial Abs (anti-endometrial autoantibodies), interleukin-6 (IL-6), CA-19.9 and CA-125) were evaluated by enough studies to provide a meaningful assessment of test accuracy. None of these tests was accurate enough to replace diagnostic surgery. Several studies identified biomarkers that might be of value in diagnosing endometriosis, but there are too few reports to be sure of their diagnostic benefit. Overall, there is not enough evidence to recommend testing for any blood biomarker in clinical practice to diagnose endometriosis. Generally, the reports were of low methodological quality, and most blood tests were only assessed by a single or a small number of studies. When the same biomarker was studied, there were significant differences in how studies were conducted, the group of women studied and the cut-offs used to determine a positive result. More high quality research trials are necessary to accurately assess the diagnostic potential of certain blood biomarkers, whose diagnostic value for endometriosis was suggested by a limited number of studies.
We found 24 relevant studies of which 17 provided data for our primary outcome. Six studies (434 children) provided data for the procalcitonin test; 13 studies (1638 children) provided data for the C-reactive protein test, and six studies (1737 children) provided data for the erythrocyte sedimentation rate test. We found all three tests to be sensitive (summary sensitivity values ranged from 86% to 95%), but not very specific (summary specificity values ranged from 38% to 71%). None of the tests were accurate enough to allow clinicians to confidently differentiate upper from lower urinary tract disease.
Twelve trials met the inclusion criteria. The meta-analysis of seven trials suggests a significant treatment effect for the total score on the Hamilton Anxiety Scale in favour of kava extract. Few adverse events were reported in the reviewed trials, which were all mild, transient and infrequent. These data imply that, compared with placebo, kava extract might be an effective symptomatic treatment for anxiety although, at present, the size of the effect seems to be small. Rigorous trials with large sample sizes are needed to clarify the existing uncertainties. Particularly long-term safety studies of kava are needed.
We searched electronic databases and conference abstracts to identify any relevant studies. We include 44 studies, which tested and compared the cure rates of SEQ therapy against STTs. Our review covers research up to April 2015. The review indicates that before 2008 the cure rate for SEQ was higher than for STT. However, the cure rate of both treatments is lower than we would wish. The review found that effectiveness depended on several factors, including the geographic region of the study, bacterial resistance, and the date of the study. For example, we found a reduction in the cure rate over time in both STT and SEQ therapies, with a stronger reduction for SEQ. This meant that in the studies published after 2008, SEQ was not more effective than triple therapy when they were both given for 10 days. The evidence collected and combined in this review does not support the use of SEQ therapy, as its effectiveness can be matched and even improved on by better STTs (given for 10 or 14 days, or high acid inhibition). Results for SEQ were only partially successful. We need to find another form of therapy to provide the best treatment for patients. The studies included in this review were of mixed quality, but our analyses do not suggest that study quality was influencing cure rates.
The review of trials found that there was not enough evidence that postnatal phenobarbital is effective in preventing IVH. Furthermore, phenobarbital suppresses breathing in infants who are breathing spontaneously, causing a need for mechanical ventilation.
The results from this review indicate that CIC at low to moderate doses improves lung function and reduces asthma symptoms compared to placebo, but the short duration of the studies means that there is a lack of information about the impact on asthma exacerbations. Thus the currently recommended doses of CIC of 100-200 mcg daily would seem appropriate. However, the number of studies in the higher dose range are low and further studies are therefore required in adults and children to determine whether higher CIC doses will give significant benefit without increasing adverse events. It will also be important to determine in clinical studies how CIC compares to the other currently available ICS in terms of efficacy and safety in asthmatic adults and children in order to determine the precise role of CIC therapy in asthma. The published data are insufficient to assess the reputed safety advantage of ciclesonide, and better assessment and reporting in studies is required to address this important question.
The evidence is current to August 2018. We found three studies (specifically, randomized controlled trials) with a total of 2,261 people. The studies compared docetaxel (an anti-cancer drug) and hormone therapy to hormone therapy alone. Taxane-based chemotherapy in addition to hormone therapy likely improves overall and cancer-specific survival and reduces disease progression. There may also be a small but unimportant improvement in quality of life at 12 months. There may also be an increase in side effects when people are treated with taxane-based chemotherapy. We judged the certainty of the evidence to be moderate for time-to-death from any cause, risk of prostate cancer-specific death and the time to disease progression. This means that our estimates are likely to be close to the truth, but there were limitations in the studies that reduce our confidence in the results. The certainty of the evidence was low for Grade III to V adverse events (side effects), adverse events of all grades, people stopping treatment due to adverse events, and quality of life. This means that the true effect of the treatment may be substantially different from what this review shows, because of limitations in the studies and imprecision (variability in estimates).
We found eight randomised controlled trials that compared the effects between morning and evening statin administration in 767 people. Each trial evaluated different types and doses of statins. These trials were published between 1990 and 2013 and were conducted in the USA, Canada, Germany, Finland, Japan, South Korea and Thailand. This review includes evidence identified up to November 2015. No trials assessed CVD clinical events or deaths. Evaluation of the available evidence indicated that there were no differences between evening or morning administration of statins in terms of lipid levels (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides). Additionally, there was no difference in the rate of adverse events associated with statins between both regimens. The evidence in this review is of low quality because of study limitations and imprecision. Larger studies are required to confirm these results.
We searched for all randomised controlled trials to March 2016 that compared at least one of the newer techniques with surgery, when treating short saphenous vein (SSVs; found in the lower leg) varices. We found three trials comparing EVLA with surgery; one trial compared UGFS with surgery, but none reported RFA. The main measures (outcomes) were recanalisation (blood flowing in the veins again) or persistence of reflux (due to failure of treatment) at six weeks; recurrence of reflux at one year; clinical evidence of recurrence (presence of new varicose veins) at one year; repeat treatment due to failure; quality of life (QoL) at six weeks and one year after the treatment; and complications after treatment. The EVLA versus surgery comparison included 311 participants: 185 received EVLA and 126 received surgery. In the UGFS comparison, each treatment group contained 21 people. For several outcomes in the EVLA comparison, only one study provided data; consequently, this review has limited ability to demonstrate meaningful results for some planned outcomes. EVLA versus surgery: there was less recanalisation or persistence of reflux at six weeks and less recurrence of reflux at one year in the EVLA group; however, there were insufficient data to report clear differences in clinical recurrence at one year. One trial reported four participants in each group required further treatment. There was no difference between treatments in QoL. Although some participants had postoperative complications (e.g., sural nerve injury (the sural nerve is in the calf), infection, deep venous thrombosis (DVT; blood clots in veins), inflammation of the wall of the vein), most complications improved without treatment and the two cases of DVT resolved after treatment with medicines. UGFS versus surgery: there were insufficient data to detect clear differences between treatment groups for recanalisation or persistence of reflux at six weeks and recurrence of reflux at one year. Data were not available for other outcomes. For the EVLA comparison, the quality of evidence was moderate for recanalisation or persistence of reflux, QoL and complications, all at six weeks, and retreatment due to technical failure, but low for recurrence of reflux, QoL and clinical evidence of recurrence after one year. The quality of evidence was downgraded due to imprecision (small number of trials with few participants) and bias (outcome assessors aware of treatment allocation in some studies and one study recruited insufficient participants with SSV). For the UGFS comparison, evidence was low quality because one study (with few participants with SSV) offered UGFS and several participants were missing from the analysis. The main difficulty with this review was lack of data: we found a small number of trials and two trials had substantial amounts of unavailable data. Further well-designed studies are needed.
This meta analysis of six randomised clinical trials of interferon shows that even Interferon alpha is not an ideal drug for this infection. Among the 169 participants included in primary meta analysis, interferon alpha induced loss of virus, normalisation of liver tests, and improvement in the liver biopsy in more patients compared with those who were left untreated. Unfortunately, most of these patients did not have sustained response after stopping treatment. Additional analysis of two trials comparing a higher dose of interferon alpha with lower dose among randomly assigned participants showed no significant difference in outcome between the two groups. There were differences in dosage and duration of interferon alpha used among included trials as well as some other methodological weakness which places a high risk of bias in this meta analysis.
Since the early statin randomised controlled trials were reported in the 1990s, several reviews of the effects of statins have been published highlighting their benefits particularly in people with a past history of CVD. Benefits include a reduction in CVD events. Statins have also been shown to reduce the risk of a first event in otherwise healthy individuals at high risk of CVD (primary prevention) but information on possible hazards has not been reported fully. The aim of this updated systematic review is to assess the effects, both in terms of benefits and harms of statins, for the primary prevention of CVD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE until 2011. We found 18 randomised controlled trials with 19 trial arms (56,934 patients) dating from 1994 to 2008. All were randomised control trials comparing statins with usual care or placebo. The mean age of the participants was 57 years (range 28 - 97 years), 60.3% were men, and of the eight trials that reported on ethnicity, 85.9 % were Caucasian. Duration of treatment was a minimum one year and with follow-up of a minimum of six months. All-cause mortality and fatal and non-fatal CVD events were reduced with the use of statins as was the need for revascularisation (the restoration of an adequate blood supply to the heart) by means of surgery (coronary artery bypass graft ) or by angioplasty (PTCA). Of 1000 people treated with a statin for five years, 18 would avoid a major CVD event which compares well with other treatments used for preventing cardiovascular disease. Taking statins did not increase the risk of serious adverse effects such as cancer. Statins are likely to be cost-effective in primary prevention.
We searched the medical literature in order to identify studies that provided information on the above question. The authors obtained information from randomised trials only since such types of trials provide the best information if conducted well. Two review authors independently identified the trials and collected the information. The information is current to March 2013. We found four trials including 431 patients undergoing elective laparoscopic cholecystectomy who received either formal patient education (215 participants) or standard care (216 participants). The choice of whether the patient received formal patient education or standard care was determined by a method similar to the toss of a coin in order to create comparable groups of patients. The patient education included providing information by just talking to the patient but in a more formal way or by using various method of presentation. All the trials were of high risk of bias (faults in study design that can result in erroneous conclusions). Only one trial including 212 participants reported deaths after surgery. There were no deaths in either group in this trial. There was no clear evidence of an effect on pain scores at 9 to 24 hours, patient knowledge, patient satisfaction, or patient anxiety associated with education. None of the trials reported surgical complications, quality of life, percentage of patients discharged as day-procedure laparoscopic cholecystectomy, length of hospital stay, return to work, or the number of unplanned visits to the doctor. A total of 173 participants undergoing elective laparoscopic cholecystectomy underwent patient education with repeat-back (patients repeating back the information provided) (92 participants) or patient education without repeat-back (81 participants) in one trial of high risk of bias. The only outcome reported in this trial was patient knowledge. The results we found for the effect onpatient knowledge between the patient education with repeat-back and patient education without repeat-back groups were uncertain and we could not exclude possible benefits of either education or control. Due to the very low quality of the current evidence, we are uncertain as to whether formal patient education provided in addition to the standard information provided by doctors has any benefit to patients. Further well-designed randomised clinical trials are necessary. The overall quality of the evidence was very low.
This review included 16 randomised trials with a placebo control group, with over 900 children involved. The review found no evidence that single or multiple dose intravenous secretin is effective in improving the main problems seen in ASD, namely a lack of social interaction and communication and restrictive, repetitive behaviours and routines. As such, currently it should not be recommended or administered as a treatment for ASD. Further experimental assessment of secretin's effectiveness for ASD can only be justified if there is convincing new evidence that finds that secretin can influence brain function in a way that could benefit children with ASD or a link is proven between secretin and the known cause of ASD for some or all children.
We identified 44 studies comparing different antibiotics. Cefepime resulted in significantly higher mortality compared to all other antibiotics combined, at the end of patients' hospital stay or 30 days after entry into the study. The risk was 39% higher with cefepime, ranging from 4 to 86% increased risk. We did not find an explanation for this when looking into other outcomes reported in the primary studies. Piperacillin-tazobactam resulted in lower mortality than other antibiotics. The other antibiotics (ceftazidime, imipenem and meropenem) showed comparable efficacy, with a lower rate of antibiotic changes for imipenem or meropenem and a higher rate of severe diarrhea with these two antibiotics. We conclude that piperacillin-tazobactam might be the preferred antibiotic for the treatment of cancer patients with fever and neutropenia and that cefepime should not be used. Antibiotic selection (other than cefepime) depends on the individual patient and the type of bacteria prevalent in the specific hospital.
There were eight clinical trials with altogether 653 participants. Only six trials with altogether 587 participants gave information about the primary outcome measure for this review, which was change in a seven-point disability scale. Financial support came from Baxter Bioscience for one trial, research councils for two trials, the National Institutes of Health for one trial, and unstated sources for the others. According to moderate quality evidence, when we pooled the results of the six trials with the necessary information there was no significant difference in change in disability grade after four weeks. Also according to moderate quality evidence, there was no difference in the percentage of participants who died or were left disabled after one year. We considered the evidence about disability unreliable because of marked variations between the trials. In four small trials of oral corticosteroids, with 120 participants, there was significantly less improvement after four weeks with corticosteroids than without corticosteroids but we considered the evidence quality very low. By contrast, according to moderate quality evidence, in two large trials of intravenous (injected into a vein) corticosteroids with a combined total of 467 participants, there was a slight improvement in disability after four weeks, but the results allowed for the possibility of no effect. Corticosteroids were not associated with a significant increase in harm except that diabetes was significantly more common than with placebo or supportive treatment alone. Although high blood pressure is a known harmful effect of corticosteroids, high blood pressure was unexpectedly much less common in the corticosteroid-treated participants. The lack of benefit from corticosteroids is not understood but might be because the drugs have a harmful effect on muscles which counteracts the benefit from reducing inflammation in nerves. The review is assessed as up to date to January 2016.
This review includes 10 small and flawed trials that recruited a total of 388 people with chronic ankle instability. Limitations in the design, conduct and reporting of these trials meant that it was difficult to be certain that their results were valid. Three trials compared neuromuscular training with no training. These found a programme of neuromuscular training appears to provide short term improvement in functional stability. One trial testing the use of a special cycle pedal found that it did not make an important difference to function. However, none of these four trials followed-up patients after the end of treatment. Four trials compared different types of surgical intervention. There was insufficient evidence to strongly support any specific surgical procedure for treating chronic ankle instability. Two trials found that, after surgical reconstruction, early functional rehabilitation enabled patients to return to work and sports quicker than six weeks immobilisation.
Only amantadine has been tested in randomised clinical trials including participants with chronic hepatitis C. The main goal of these trials was to investigate whether amantadine as a single therapy or amantadine in combination with other antiviral therapies, compared with placebo or no intervention (with or without antiviral therapy), could increase the proportion of patients with virus eradication from the blood. This review evaluates whether amantadine versus other antiviral drugs has any beneficial or harmful effect in patients with chronic hepatitis C. The trials compared amantadine with ribavirin, mycophenolate mofetil, interferon-alpha, or interferon-gamma. The primary outcomes were the composite of all-cause mortality or liver-related morbidity and adverse events. This review includes six randomised clinical trials with a total of 581 patients. All the included trials were with high risk of bias. This review did not demonstrate any benefits or harms of amantadine on all-cause mortality or liver-related morbidity and on adverse events, but data were sparse. Compared with ribavirin, amantadine seemed to lead to more participants who fail to achieve sustained virological response (that is, undetectable hepatitis C virus RNA in serum by sensitivity testing six months after the end of treatment). This may be real or due to bias (systematic errors), but it does not seem to be due to play of chance (random errors), as trial sequential analysis confirmed the result. Compared with mycophenolate mofetil, amantadine seemed less effective in achieving end-of-treatment virological response. Compared with interferon-alpha or interferon-gamma, amantadine did not seem to offer benefits. Accordingly, the evidence from this review does not support the routine clinical use of amantadine. Therefore, it is probably better to examine the effects of other direct acting antivirals in the hepatitis C field than to conduct more randomised clinical trials on amantadine. We found no randomised clinical trials assessing other aminoadamantanes, for example rimantadine.
We found 23 studies, including a total of 2669 participants, which reported effects of psychological treatment compared to a control group without psychological treatment on pain intensity, use of pain medication, mental distress, mobility, or time to extubation after surgery. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. We do not know if psychological treatment reduces pain intensity, enhances mobility, or decreases intubation time after open heart surgery. This is because there were not enough data to answer some parts of our review question, because there were problems with the design of some studies, or because results were conflicting. We only found very low to moderate-quality evidence for these outcomes. We found moderate-quality evidence that psychological treatment could reduce mental distress. This means that we are moderately certain about the results because there were psychological treatments that clearly reduced distress whereas others did not. The evidence in our review is current to February 2017.
One hundred and eighty-five intervention studies of 12,210 individuals lasting four to 1100 days were included, which evaluated at least one of the effect measures. Participants were healthy or had elevated blood pressure. Longitudinal studies have shown that the effect of reduced salt intake on BP is stable after at maximum seven days and population studies have shown that very few people eat more than 14.5 g salt per day. Therefore, we also perfomed subgroup sub-analyses of 125 studies with a duration of at least seven days and a salt intake of maximum 14.5 g. Forty-four studies did not mention support. One hundred and twenty-two studies were supported by public foundations. Twelve studies were supported by the pharmaceutical industry and one study by an electronic company. Six studies were supported by food industry organisations. The mean dietary sodium intake was reduced from 11.5 g per day to 3.8 g per day. The reduction in SBP/DBP in people with normotension was about 1/0 mmHg, and in people with hypertension about 5.5/2.9 mmHg. In contrast, the effect on hormones and lipids were similar in people with normotension and hypertension. Renin increased 1.60 ng/mL/hour (55%); aldosterone increased 97.81 pg/mL (127%); adrenalin increased 7.55 pg/mL (14%); noradrenalin increased 63.56 pg/mL (27%); cholesterol increased 5.59 mg/dL (2.9%); triglyceride increased 7.04 mg/dL (6.3%). Only randomised controlled trials were included and the basic grade of evidence was therefore considered to be high, although the grade of evidence was downgraded in some of the smaller analyses. In general, the description of the randomisation procedure was insufficient, introducing a bias which could exaggerate the effects, but many of the studies were published in a period where it was not customary to report such descriptions. The majority of studies were open, but the outcomes of these did not differ from the outcomes of the double-blind studies. Almost all individual studies of participants with normal blood pressure (BP) show no significant effect of sodium reduction on BP, whereas a large number of studies in people with hypertension did show significant effect of sodium reduction on BP. Thus, there was a high grade of consistency between the outcomes of the individual studies and the outcomes of the meta-analyses. Sensitivity analyses of studies lasting at least one week (the time of maximal efficacy) confirmed the primary analyses. Finally, the impact of commercial interests on the outcomes was negligible.
Thousands of people with schizophrenia have participated in studies and therefore we are reasonably sure that it is a potent antipsychotic drug and as good as similar older drugs. Most people taking it do experience adverse effects, but this also applies to other older drugs. Not enough comparisons with newer generations of drugs have been undertaken to be sure of how trifluoperazine compares to them.
In this review, we evaluated 16 studies (involving 4759 participants) of healthcare workers or volunteers (a 'stroke liaison worker') providing education and social support (including counselling) and liaison with services. Overall, there do not appear to be any significant benefits for patients in terms of their perceived health, mood, activities or participation. Patients appeared to be more satisfied that someone had really listened to them, and carers appeared to be more satisfied with aspects of the care provided. It also appears that patients with mild to moderate disability may benefit from a reduction in disability and death as a result of the input from the stroke liaison worker. The reason for this is not yet clear and further research is required.
Four studies with 753 participants were included in this review. Three compared respite care to no respite care and one compared respite care to polarity therapy, a type of touch therapy. All studies included people with dementia and their caregivers. We were not able to pool the results of the studies as there were so few studies and they measured the outcomes in different ways. All the studies reported outcomes for the caregiver, but only one reported outcomes for the person with dementia. The three studies that compared respite care to no respite care found no evidence of any benefit of respite care for people with dementia or for their caregivers for any outcome, including rates of institutionalisation and caregiver burden. The study that compared respite care to polarity therapy found that polarity therapy decreased caregiver perceived stress but that there was no difference between polarity therapy and respite care for other measures of psychological health and other caregiver outcomes. A host of methodological problems were identified in the available trials. One study did not report data that could be analysed, the remaining three studies were very small and had a very short duration. Further methodologically sound research is needed before any firm conclusions can be drawn.
Key results: A single study showed some benefit of the inhaled ICS-LABA combination over high-dose ICS in terms of indices of clinical stability such as dyspnoea (shortness of breath), cough-free days and number of exacerbations but failed to show significant improvement in lung function or microbiology. No data are available on children with bronchiectasis or adults with bronchiectasis during an exacerbation phase. Until further evidence becomes available, we recommend that use of combined ICS-LABA should be individualised according to the presence or likelihood of co-existing asthma features and risks of medications. Quality of the evidence: This review is based on a single study, hence the quality of evidence is substantially limited. Bottom line: The decision to use combined ICS-LABA in bronchiectasis must be made for individual patients on the basis of the presence or absence of bronchial hyperreactivity, until further randomised controlled trials are conducted to answer this important question.
In this review, we found only one study that focused on the effects of healthcare professionals using email to communicate with each other. This study included 327 patients and 159 healthcare providers, and compared an email reminder for physicians with usual care. It found that healthcare professionals who received an email reminder were more likely to provide guideline-recommended osteoporosis treatment than those who did not, and this may or may not have improved patient care. We were unable to properly assess its impact on patient behaviours or actions as the results were mixed. The study did not measure how email affects health services, or whether email can cause harms. This evidence is current to August 2013. As there is a lack of evidence for the effects of healthcare professionals using email to communicate with each other, high-quality research is needed to evaluate the use of email for this purpose. Future research should look at the costs of using email and take into account ongoing changes in technology.
We searched the scientific literature for randomised controlled trials (experiments that randomly allocate participants to one of two or more treatment groups) looking at the effectiveness of education-based treatments compared with no education in people of all ages with CHD. We included nine new trials which involved 8215 people with coronary heart disease that compared patient education with no education. We included a total of 22 trials that studied 76,864 people with heart disease, most of whom had survived heart attack, and had undergone heart bypass surgery or angioplasty (a procedure which opens blocked vessels that supply blood to heart muscle). Sixteen studies reported sources of funding; six did not report funding sources. One study was funded by an industrial sponsor, four by health insurance companies and 11 by government or public sources. Findings of this update are similar to the last review version (2011). Patient education, as part of a cardiac rehabilitation programme, does not contribute to fewer deaths, further heart attacks, heart by-pass or angioplasty, or admission to hospital for heart-related problems. There is some evidence of fewer other heart-related events and improvements in health-related quality of life with education-based interventions. Individual causes of death were not reported, so we were unable to determine how many people in the studies died from heart-related causes or other causes of death. Although there is insufficient information at present to fully understand the benefits or harms of patient education for people with heart disease, our findings broadly support current guidelines that people with heart disease should receive comprehensive rehabilitation that includes education. Further research is needed to evaluate the most clinically and cost-effective ways of providing education for people with heart disease. Overall, evidence was assessed as very low to moderate quality.
Characteristics of the included studies. The search of the medical literature was done in March 2014. We found two randomised controlled trials (RCTs) with 106 participants comparing oocyte vitrification versus slow freezing. Neither study reported live births or adverse events as outcomes. One reported ongoing pregnancy and both reported clinical pregnancy. Key results. The clinical pregnancy rate was higher in the oocyte vitrification group than in the slow freezing group. The effect of vitrification compared to slow freezing on ongoing pregnancy rates was only reported in the one small study, with inconclusive findings. Quality of the evidence. The quality of the evidence was rated as moderate for clinical pregnancy and low for ongoing pregnancy. The evidence was limited by imprecision.
We found 51 studies, mostly from high-income countries and mostly describing women's perspectives. We assessed our level of confidence in each finding using the GRADE-CERQual approach. We had high or moderate confidence in many of our findings. Where we only had low or very low confidence in a finding, we have indicated this. Labour companions supported women in four different ways. Companions gave informational support by providing information about childbirth, bridging communication gaps between health workers and women, and facilitating non-pharmacological pain relief. Companions were advocates, which means they spoke up in support of the woman. Companions provided practical support, including encouraging women to move around, providing massage, and holding her hand. Finally, companions gave emotional support, using praise and reassurance to help women feel in control and confident, and providing a continuous physical presence. Women who wanted a companion present during labour and childbirth needed this person to be compassionate and trustworthy. Companionship helped women to have a positive birth experience. Women without a companion could perceive this as a negative birth experience. Women had mixed perspectives about wanting to have a male partner present (low confidence). Generally, men who were labour companions felt that their presence made a positive impact on both themselves (low confidence) and on the relationship with their partner and baby (low confidence), although some felt anxious witnessing labour pain (low confidence). Some male partners felt that they were not well integrated into the care team or decision-making. Doulas often met with women before birth to build rapport and manage expectations. Women could develop close bonds with their doulas (low confidence). Foreign-born women in high-income settings may appreciate support from community-based doulas to receive culturally-competent care (low confidence). Factors affecting implementation included health workers and women not recognising the benefits of companionship, lack of space and privacy, and fearing increased risk of infection (low confidence). Changing policies to allow companionship and addressing gaps between policy and practice were thought to be important (low confidence). Some providers were resistant to or not well trained on how to use companions, and this could lead to conflict. Lay companions were often not integrated into antenatal care, which may cause frustration (low confidence). We compared our findings from this synthesis to the companionship programmes/approaches assessed in Bohren’s review of effectiveness. We found that most of these programmes did not appear to address these key features of labour companionship. We searched for studies published before 9 September 2018.
This review found five poor to moderate quality studies, of which four with a total of 282 women provided data. There was not enough evidence to say if systematic desensitisation worked better than another treatment. Further studies including larger numbers of women are needed to show if systematic desensitisation if effective for the treatment of women with vaginismus.
The review included 16 randomised controlled trials (more than 1800 women) that compared these procedures for treating couples with non-tubal subfertility. Only three trials reported live birth. The evidence is current to September 2013. No trial reported its funding source, but one reported no conflict of interest, and one stated that it had received no commercial funding. No clear evidence suggests any difference between IUI and FSP with respect to their effectiveness and safety in the treatment of couples with non-tubal subfertility. However, a high level of uncertainty due to lack of data is evident in the findings. The overall quality of the evidence was rated as low for most outcomes, largely because of the small quantity of available data.
Overall, the trials were at high risk of bias (that is, there is a potential to arrive at wrong conclusions). This was because it was not clear how the randomisation was performed, whether the people assessing the outcomes were aware of the group to which the participants belonged, and whether all participants were included in the analysis. The overall quality of evidence was very low as the trials were at high risk of bias and there were few trials to assess whether only studies with negative results were published. There is very low quality evidence that surgical resection increases survival and decreases costs compared to palliative treatments for patients with locally advanced pancreatic cancer with involvement of veins. In selected patients pancreatic resection could be considered for patients with locally advanced pancreatic cancer who are willing to accept the potentially increased complications associated with the surgical procedure and when sufficient expertise is available. Further randomised controlled trials are necessary to obtain more precise results and to assess the quality of life of patients and the value for money of surgical removal versus other treatments for locally advanced pancreatic cancer.
A recent trial of protein containing synthetic surfactant compared to protein free synthetic surfactant suggests that these protein containing synthetic surfactants help prevent respiratory distress syndrome and may or may not lead to a decrease in lung injury (chronic lung disease). Other clinical outcomes were similar. Further studies will help refine recommendations concerning use of protein containing synthetic surfactants.
Flupenthixol was first made available in the UK in 1965 and it has been used to treat schizophrenia for nearly five decades. It is available both as a tablet and a long-acting injection. Having been investigated in numerous studies, flupenthixol was found to be effective and well tolerated by people with schizophrenia. The main side effects are shaking, restlessness or the inability to sit still, a dry mouth and some weight gain. Although this drug has been available for decades, few systematic reviews exist on flupenthixol. The effects of this drug in helping people cope with the symptoms of schizophrenia are not currently measured, quantified and known. The review could include only one small study, which was limited and 13 years old. The number as well as the quality of the study was low; for the main outcomes of interest the authors could not rate the quality of evidence at all, as the study did not report on the outcomes of interest for the 'Summary of findings' table. Flupenthixol was compared with chlorpromazine. There was no clear difference in efficacy, nor was there clear information on: increasing their use of services; people’s satisfaction with treatment; quality of life; or costs and cost effectiveness. Flupenthixol is widely available and inexpensive. It is perhaps understandable that it remains one of many drugs used for treating people with serious mental illnesses. This is because the use of flupenthixol is based more on clinical experience, and the decisions of psychiatrists are based on large scale research studies and evidence-based information. The effectiveness and benefits of flupenthixol over chlorpromazine remain largely unknown and incomplete. Large randomised trials could be helpful in increasing knowledge about this drug. This plain language summary has been written by Benjamin Gray, Service User Expert, Rethink Mental Illness.
One study (19 participants) met our inclusion criteria. It showed that high-flow nasal cannula therapy is well tolerated as a treatment for bronchiolitis. Oxygen saturations (blood oxygen levels) were better at eight and 12 hours in participants receiving high-flow nasal cannula therapy than in those receiving oxygen therapy via a head box, but were similar between groups at 24 hours, although this may have been due to higher oxygen flow rates in the high-flow nasal cannula group. There was no clear evidence of a difference between the two groups in the duration of oxygen therapy, length of hospitalisation and time to discharge. No adverse events were reported in either group. There is insufficient evidence to determine the effectiveness of high-flow nasal cannula therapy for treating bronchiolitis in infants. The included study provides some indication that HFNC therapy is feasible and well tolerated. However, our evidence is based on one low-quality, small study with uncertainty about the effects and some possibility of bias arising from the study methods. Further research is required to determine the role of high-flow nasal cannula therapy in the management of bronchiolitis in infants. The results of six ongoing studies identified will contribute to the evidence in future updates of this review. The evidence is current to May 2013.
We included 45 studies, and based on the criteria for a positive PET-CT scan, we performed two main analyses. In the 18 studies (2823 participants) in the Activity > background group, PET-CT was found to accurately identify 77.4% (95% CI 65.3 to 86.1) of the participants with NSCLC spread beyond the N1 nodes and 90.1% (95% CI 85.3 to 93.5) of the participants without spread beyond the N1 nodes. In the 12 studies (1656 participants) in the SUVmax of ≥ 2.5 group, PET-CT accurately identified 81.3% (95% CI 70.2 to 88.9) of the participants with spread beyond the N1 nodes and 79.4% (95% CI 70 to 86.5) of the participants without spread beyond the N1 nodes. However, the results varied a lot between the studies in each analysis, and the quality and size of the studies themselves, country of study origin, percentage of participants with adenocarcinoma, FDG dose, and type of PET-CT scanner influenced the results. We believe that the results of this review show that the accuracy of PET-CT is insufficient to allow management based on PET-CT alone.
We ran electronic searches up to January 2015 for trials randomising people with schizophrenia or schizophrenia-like disorders to receive music therapy or standard care. We found and checked 176 potential studies. Eighteen trials with a total of 1215 participants met the review requirements and provided useful data. The evidence currently available is of low to moderate quality. The results of these studies suggest that music therapy improves global state and may also improve mental state, functioning, and quality of life if a sufficient number of music therapy sessions are provided. Music therapy seems to help people with schizophrenia but further research is needed to confirm the positive effects found in this review. This research should especially address the long-term effects of music therapy, the quality of music therapy provided and measure outcomes relevant to music therapy.
Researchers have studied the ability of various drug treatments to prevent the development of chronic pain after surgery and this systematic review evaluated published studies in this field. Available studies suggest a modest effect of ketamine, compared to placebo, for prevention of chronic pain after surgery, however small study size could lead to an overestimation of this effect. Studies of other drugs such as gabapentin and pregabalin did not suggest the same preventative effect. Additional large studies using improved research methods are necessary to more clearly identify treatments that are beneficial for preventing chronic postsurgical pain.
This review of 17 trials found evidence that aciclovir is efficacious in the prevention and treatment of HSV infections, in terms of preventing clinical/culture positive HSV infections, reduction in healing time, duration of viral shedding and relief of pain. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that for prevention, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.
In June 2014 we searched for as many relevant medical studies as we could find that had a robust design (randomised controlled trials) that had compared hydrogel dressings with other treatments for pressure ulcers. We found 11 studies involving a total of 539 participants. From the results of these studies we could not tell whether hydrogel wound dressings heal pressure ulcers more quickly or slowly than other types of dressing or topical treatments. Generally, the studies we found were small and the results inconclusive. Some studies lacked information about how they were conducted and it was difficult to tell whether the results presented were robust. More research of better quality is needed before it can be determined whether hydrogel dressings are better or worse at healing pressure ulcers than other types of dressings or topical treatments.
In many countries in the industrialised world there has been a huge growth in the prescription of medication for people with mental health problems, taken orally as a tablet or by injection. Atypical and second generation antipsychotic drugs have become ever more popular, because they are thought to help people with mental health problems who do not respond quite so well to initial treatment. These newer drugs hold the promise of both reducing symptoms, such as hearing voices or seeing things, and reducing problematic side effects, such as sleepiness, weight gain, and shaking. However, there is little research and comparison of the ways in which drugs differ from one another. This review examines the effectiveness of aripiprazole with other new antipsychotics.  Originally the review included 12 research trials. After an update search carried out in November 2012, 162 trials were added. Most of these trials were from China and although new data were added to the review, overall conclusions did not change. The review now has five comparisons with aripiprazole being compared with clozapine, olanzapine, quetiapine, risperidone and ziprasidone. For people with schizophrenia it may be important to know that aripiprazole may not be as good or effective as olanzapine but that it has less side effects. Aripiprazole is similar in effectiveness to risperidone and somewhat better than ziprasidone. Aripiprazole had less side- effects than olanzapine and risperidone (such as weight gain, sleepiness, heart problems, shaking and increased cholesterol levels). Aripiprazole was not as good as ziprasidone for dealing with restlessness or people’s inability to sit still. Comparison with other antipsychotic drugs as a group showed that people preferred taking aripiprazole. However, people with schizophrenia as well as mental health professionals and policy makers should know that the evidence is limited and mostly of low or very low quality. More trials and research is required, including on outcomes such as: quality of life; the views of service users and carers; and patient preference. This plain language summary has been written by a consumer from Rethink Mental Illness, Benjamin Gray. Email: [email protected]
In this review, we assessed 29 studies that evaluated the effects of self management. Patients in these studies were followed for two to 24 months. Twenty-three studies had a control group that received usual care. A total of 3189 patients participated in these studies. In six studies, different components of self management were compared on a head-to-head basis. Content and duration of the self management programmes were diverse. Analysis of the studies revealed that self management training improved health-related quality of life in patients with COPD compared with usual care. Also, the number of patients with at least one hospital admission related to lung disease and other causes was reduced among those who participated in a self management intervention. These patients also experienced less shortness of breath. We found trials that compared different types of self management interventions versus each other. We had hoped that these trials would help us identify the most effective components of self management. However, all interventions were different, and we were unable to draw out the key themes. The studies assessed in this review were diverse. Self management programmes differed in content and duration. Also, types of participants differed across studies. Therefore, no clear recommendations on the most effective content of self management training can be made at this time.
Only two small randomised clinical trials on this topic were identified. The trials were not large enough in terms of sample size or length of follow up to allow changes in mortality to be adequately evaluated. Glucocorticosteroids were associated with improvement in serum markers of inflammation and liver histology, both of which were of uncertain clinical significance. Glucocorticosteroids were also associated with adverse events, including reduced bone mineral density. Further trials are necessary if the effectiveness of glucocorticosteroids is to be properly evaluated.
We studied whether a difference could be seen in the growth of children with persistent asthma who were using different doses of the same ICS molecule and the same delivery device. We found 22 eligible trials, but only 10 of them measured growth or other measures of interest. Overall, 3394 children included in the review combined 17 group comparisons (i.e. 17 pairs of groups of children with mild to moderate asthma using a particular dose and type of steroid in 10 trials). Trials used different ICS molecules (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) either on their own or in combination with a long-acting beta2-agonist (a drug used to open up the airways) and generally compared low doses of corticosteroids (50 to 100 μg) with low to medium (200 μg) doses of corticosteroids (converted in μg HFA-beclomethasone equivalent) over 12 to 52 weeks. We found a small but statistically significant group difference in growth over 12 months between these different doses clearly favouring the lower dose of ICS. The type of corticosteroid among newer molecules (ciclesonide, fluticasone, mometasone) did not seem to influence the impact on growth over one year. Differences in corticosteroid doses did not seem to affect the change in height, the gain in weight, the gain in body mass index and the maturation of bones. This review is based on a small number of trials that reported data and were conducted on children with mild to moderate asthma. Only 10 of 22 studies measured the few outcomes of interest for this review, and only four comparisons reported growth over 12 months. Our confidence in the quality of evidence is high for this outcome, however it is low to moderate for several other outcomes, depending on the number of trials reporting these outcomes. Moreover, a few outcomes were reported only by a single trial; as these findings have not been confirmed by other trials, we downgraded the evidence for these outcomes to low quality. An insufficient number of trials have compared the effect of a larger difference in dose, for example, between a high dose and a low dose of ICS and of other popular molecules such as budesonide and beclomethasone over a year or longer of treatment. We report an ICS dose–dependent reduction in growth velocity in prepubescent school-aged children with mild to moderate persistent asthma. The choice of ICS molecule (mometasone, ciclesonide or fluticasone) was not found to affect the level of growth velocity response over a year. The effect of corticosteroids on growth was not consistently reported: among 22 eligible trials, only four comparisons reported the effects of corticosteroids on growth over one year. In view of parents' and clinicians' concerns, lack of or incomplete reporting of growth is a matter of concern given the importance of the topic. We recommend that growth be systematically reported in all trials involving children taking ICS for three months or longer. Until further data comparing low versus high ICS dose and trials of longer duration are available, we recommend that the minimal effective ICS dose be used in all children with asthma.
To assess the efficacy of MBUs we systematically searched for any randomised trials of MBUs compared to standard care. We found no trials involving either mothers suffering from post partum psychosis or severe post natal depression. Anecdotal results from a 1961 trial did suggest a beneficial effect, but non-randomised data from over 40 years ago is difficult to apply to today's care. Such lack of data is of concern as MBUs are expensive to set up and run. If they are to be the 'gold standard' of care for mothers and their babies, their effectiveness needs to validated. Good quality, relevant research is urgently needed.
The evidence in this review is current to November 2013. We included five studies with a total of 266 participants. All participants were adult stroke survivors who lived in the community or a care home. Programmes to improve community ambulation consisted of walking practice in a variety of settings and environments in the community (three studies), or an activity indoors that mimicked community walking (three studies). Three studies were funded by government agencies, and two had no funding. The term 'participation' refers to the ability of a person to engage in activities that are meaningful to them, such as leisure activities, paid or volunteer work, or socialising with others. For the primary outcome of participation we could not be sure whether the intervention improved participation compared with control (two studies). When considering how fast a person walks, it is unclear if the speed of walking may increase with a community ambulation intervention ( four studies). Based on the included studies, the effect of the intervention on the ability to walk, how far people could walk in six minutes or their confidence in walking is unclear. There is currently insufficient evidence to establish the effect of community ambulation interventions or to support a change in clinical practice. No adverse effects of the interventions were reported in any of the included studies. We considered the quality of the evidence to be low across the studies for both the participation and walking speed outcomes. There were some study design considerations which led to the low score, such as who knew what group the participants were in, and the number of people who dropped out of the studies. Also, we included a small number of studies in this review, which limits how the results can be interpreted. More research is needed in this area.
In November 2017, we searched for clinical trials where ketorolac was used to treat pain after surgery in children. We found 13 studies, enrolling 920 children, that met our requirements for the review. The studies were quite different in their design, the dose of ketorolac, the timing (during or after surgery) and number of doses given, the type of surgery, and to what ketorolac was compared (either a placebo (a dummy treatment, such as a bag of fluid) or another drug). There was not enough information for a statistical analysis of the assessments in which we were most interested, that is, the number of children with at least 50% pain relief; or the average pain intensity (a measure of a patient's pain that asks the patient to rate how much pain they have, often on a scale of 0 for 'no pain' to 10 for 'worst pain imaginable'). Four studies individually reported that ketorolac was better at reducing pain intensity than placebo, but the studies were small and had various design issues. There was more information for other assessments, such as the number of children who needed rescue medication (additional pain medication that is given if the study medication is not helping the person's pain sufficiently), and how much of this rescue medication was used. Fewer children needed rescue medication in the ketorolac group than those who received placebo, although the result was not statistically different. During the four hours after they received study medications, children receiving ketorolac needed slightly less rescue pain medication than those who had received placebo. There was not enough information about ketorolac in direct comparisons with other medications. There was also not enough information in the studies for us to make a good assessment of side effects and serious side effects when ketorolac was used in this setting. Serious side effects in those receiving ketorolac included bleeding, but it didn't occur often enough for us to make any firm conclusions. Very few children dropped out of the studies because of side effects. This is normal in studies where participants are only in the study for a short period of time. We rated the quality of the evidence as very low, due to methodological issues with many of the studies, differences in study designs, and low overall numbers of children enrolled. Very low-quality evidence means that we are very uncertain about the results.
we searched medical databases and found one study for inclusion in this review. Preterm infants born before 32 weeks' gestation (32 weeks from the first day of the woman's last period (menstruation) to the current date) who had clamping of the umbilical cord delayed for 60 seconds after birth were selected at random to enter a group of babies who received breathing support and a group of babies who did not receive breathing support. The breathing support was given after birth of the baby and before the cord was clamped. Breathing support was the use of CPAP for infants breathing on their own or applying intermittent airwaypressureto expand the lungs in babies not breathing well on their own. Most of the study infants (83%) were delivered by caesarean section. the single study included in the review did not provide sufficient evidence either for or against the use of breathing support before cord clamping. the quality of evidence was low, mainly because more infants need to be studied for definite conclusions.
This review aimed to find out whether there is good evidence that any of these work. We searched for good quality studies that involved adult patients (18 or older) who had experienced hiccups for 48 hours or more. Our conclusion is that there is insufficient evidence to recommend a particular treatment for hiccups. There is a need for randomised controlled studies to identify which treatments might be effective or harmful in treating persistent hiccups.
We included three randomised controlled studies with a total of 128 participants in this review. The duration of zinc supplementation ranged between four and 12 weeks. No study reported on our patient-important key outcomes (new onset of type 2 diabetes mellitus, side effects, health-related quality of life, all-cause mortality, diabetic complications, socioeconomic effects). The effects of zinc supplementation are uncertain regarding insulin resistance and lipid levels in the blood (mainly cholesterol and triglycerides). The overall quality of the included studies was unclear because study authors did not provide important information for us to judge how the studies were performed (unclear risk of bias in most cases). In addition, the number of studies and participants is low and the study authors did not investigate important outcomes such as new onset of type 2 diabetes mellitus or side effects of zinc supplementation. This evidence is up to date as of March 2015.
This review found that it is highly effective even in low doses. The effect does appear to increase with higher doses, but these improvements are small. This drug is associated with symptoms such a thrush, sore throat and hoarseness and these get worse with higher doses. In people with severe asthma who need oral steroid tablets to control their asthma, it can reduce the dose of oral steroids they need and improve their asthma at the same time. However, high or very high doses are needed for this effect. The drug appears to work in children and adults.
We included eight studies with a total of 353 boys and girls, who ranged in age from 1 month to 13 years. These studies had been published up to June 2015. Three studies compared nerve block with sham block. Three studies compared nerve block with injected analgesics, and two studies compared nerve block with local anaesthesia. The children who received the infraorbital nerve block (with lignocaine or bupivacaine) had less pain and more time between finishing surgery and needing more analgesics. These children also had less need for analgesics than those who received the sham block. The children who received the infraorbital nerve block also had less pain and were able to eat sooner than those who received injected (intravenous) analgesics. The nerve block did not appear to alter heart rate, breath rate, and blood pressure. Five out of eight studies found no unwanted side effects after the nerve blocks; the other three studies did not mention side effects. The overall quality of the evidence was low or very low due to the small number of children included in the studies and differences between the studies (heterogeneity) regarding the types of intervention, the observation time, and the forms of measuring and describing the outcomes. Further studies with larger numbers of children are needed.
We searched scientific databases for studies comparing TT versus a placebo (an inactive or pretend treatment) or no treatment in people with Trypanosoma cruzi infection. The search is current to February 2014. We identified 13 studies comparing the outcomes of 4229 people after receiving TT or placebo. Five of these studies were from Argentina, five from Brazil, one from Venezuela, one from Chile and one from Bolivia. Receiving TT was associated with a 50% to 90% smaller chance of having circulating antibodies or parasitic material, as compared with non-treated people. However, the results on progression towards Chagas disease or death indicate smaller benefits. Furthermore, the results were also statistically inconclusive, did not rule out potential harm and had substantial variation across studies conducted in different countries or testing different drugs. About one in five individuals treated abandoned the treatment and one in 40 treated individuals had a severe reaction (needing hospitalisation, additional treatments or interruption of this treatment). We conclude that although TT may reduce the progression of Chagas disease, better quality studies are warranted before its use can be generally recommended for chronically infected individuals. New data should bring more certainty of the efficacy of TT and provide a precise evaluation of the balance between benefits and harms. Because of the variations across studies, these studies should include populations from more regions and test newer drugs. Only 25% of these data came from good-quality studies. Although most studies were published since 2000, all studies tested drugs developed in the 1960s.
Overall, the trials suggested an improvement in the symptoms of leg pain, oedema and pruritus with horse chestnut seed extract when taken as capsules over two to 16 weeks. Six placebo-controlled studies (543 participants) reported a clear reduction of leg pain when the herbal extract was compared with placebo. Similar results were reported for oedema, leg volume, leg circumference and pruritis. The other studies which compared the extract with rutosides (four trials), pycnogenol (one trial) or compression stockings (two trials) reported no significant differences between the therapies for leg pain or a symptom score that included leg pain. The herbal extract was equivalent to rutosides, pycnogenol and compression on the other symptoms with the exception that it was inferior to pycnogenol on oedema. The adverse events reported (14 trials) were mild and infrequent. They included gastrointestinal complaints, dizziness, nausea, headache and pruritus, from six studies.
The evidence is current as of December 2017. We searched for studies that randomly allocated people with aPL antibodies and without any previous thrombotic event to different treatments, including anticoagulants, antiplatelet drugs, or both. We identified nine studies involving 1044 participants. The studies took place in several different countries. One study was multicentred and had a variety of funding sources. In two studies aspirin was compared with placebo (dummy treatment). Four studies compared an anticoagulant with or without aspirin with aspirin alone. The remaining studies compared combinations of antiplatelet agents, anticoagulants, other treatments, or two different doses of the same drug. The majority of the studies concerned women with aPL antibodies and a history of pregnancy failure. One study included non-pregnancy-related cases, and one study included pregnancy-related cases and other patients with positive results for aPL antibodies. We summarised the effects of the treatments using the following comparisons: aspirin only versus placebo, anticoagulant only or with aspirin versus aspirin only, aspirin with anticoagulant versus placebo or other treatment. We found no clear differences in the number of individuals with thrombotic events in the compared groups. One study revealed an increased risk of minor bleeding (such as nasal bleeding or intensified menstruation) in participants receiving aspirin and anticoagulant. All other analyses did not show any meaningful differences in the number of participants with bleeding. None of the studies reported on risk of death or quality of life. We found no clear difference between the groups in any of the comparisons for unwanted effects other than bleeding, where this information was reported; the more common of these effects included mild gastrointestinal symptoms in the aspirin group and allergic reactions in the aspirin with anticoagulant group. We assessed none of the studies as at low risk of bias because of methodological concerns or reporting of the results. We judged the overall quality of evidence to be low to moderate, it was downgraded due to unclear or high risk of bias, small number of studies and imprecise results.
After a wide search, we identified 13 randomised studies that included 85 participants with McArdle disease. This is an update of a review first published in 2004. We found no new trials at this update. The review found no benefit compared with placebo with the following treatments: D-ribose, glucagon, verapamil, vitamin B6, oral branched chain amino acids, dantrolene sodium, high-dose creatine and ramipril. Low dose creatine and ramipril produced minimal benefit for patients who also have the D/D angiotensin converting enzyme (ACE) phenotype. Taking low dose creatine supplements had a minor benefit in improving exercise tolerance in a small number of people with the condition. Taking a sugary drink before planned strenuous exercise can improve performance but this treatment is not practical for day-to-day living. A diet rich in carbohydrate may be superior to a diet rich in protein. Adverse effects were reported in four studies. Oral ribose caused symptoms suggestive of a low blood sugar including light-headedness, hunger and diarrhoea. One study of branched chain amino acids resulted in a deterioration in participants. Dantrolene was reported to cause a number of side-effects including tiredness, sleepiness, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause any side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of muscle pain. The quality of these studies was low due to the small number of participants; the largest number in one trial was 19 and one trial had only one participant. The evidence is current to August 2014.
The review found 260 studies which had recruited over 43 thousand people undergoing abdominal surgery. The studies had some limitations in relation to the number of people who remained in the studies and the possibility that the results were affected because some of the researchers in the studies knew which people had received antibiotics before surgery. However, when the results were analysed effect of prophylactic antibiotics was consistently beneficial meaning that these limitations were unlikely to have had a major impact on the nature of the overall results. Abdominal surgical wound infection in patients having operations on the large intestine occurs in about 40% of patients if antibiotics are not given. This risk can be greatly diminished by the administration of antibiotics prophylactically before surgery. The antibiotic(s) given usuallly needs to cover different types of bacteria some of which need oxygen (aerobic bacteria) and others which do not need oxygen (anaerobic bacteria).. They are usually given via a canula injected into a vein, though there is evidence that a combination of oral and intravenous antibiotics may provide more protection. This last finding raises a problem in that current clinical practice is to avoid mechanical cleansing of the colon because it is not thought to be necessary before surgery (and not popular with patients). Studies that found a benefit to oral antibiotics were done at a time when mechanical cleansing of the colon was routinely done. In the light of current practice regarding mechanical cleansing before surgery of the colon, the benefit of oral antibiotics is uncertain.
In July 2015, we searched scientific databases for clinical trials in which the effect of the end-of-life care pathway was compared with a control group that received usual care, or with trials comparing one end-of-life care pathway with another end-of-life care pathway. Participants were patients, carers and families who received care guided by an end-of-life care pathway. There were no restrictions on age of the patient, diagnosis or setting (hospital, home, nursing home). In the current review we found one Italian study, in which information about 232 patients who were dying was provided by their informal carers (friends or family). Only 34% of the participants were cared for in accordance with the pathway. Breathlessness was better controlled for patients on the Liverpool Care Pathway compared to patients not on the pathway, but this is based on evidence from one small trial. The study did not report on important outcomes such as the severity of other physical or psychological symptoms or quality of life, or if there were any side effects associated with using the end-of-life care pathway. Nor were there questions about satisfaction with care, costs of the intervention, or quality of communication between carers and healthcare providers. We judged the included study to be of very low quality due to potential biases, including: not being able to prevent participants from knowing which group they were in (usual care or the care pathway group); the large number of carers who were initially enrolled, but who did not respond to follow-up questionnaires (this was particularly true for carers of patients in the wards where the care pathway was not used (control wards)); the low proportion of patients who actually received the care pathway (intervention) as planned; and that the study only included cancer patients in Italian hospitals; therefore, results might not apply to patients with other diseases.
A search was performed of the literature in May 2013 for studies comparing the two techniques and 11 randomised controlled trials were identified which included a total of 1228 participants. These trials included participants with age-related cataract and were conducted in Europe, South America and the Far East. We evaluated these for any biases that may have affected the data, extracted data according to pre-determined criteria and performed analyses of the pooled data from all studies where possible. There were few studies that reported outcomes which met our pre-defined criteria. The studies were generally at unclear risk of bias due to poorly reported trial methods and the overall quality of the evidence for different outcomes ranged from moderate to very low. Phacoemulsification gave superior results at both three and 12-month time points. Complications were higher in the ECCE group than the phacoemulsification group. However, two out of three studies that reported costs indicated that ECCE was cheaper than phacoemulsification. In summary, on the basis of the few studies that reported outcomes that we could include in our analysis, visual outcomes were better with phacoemulsification and complications were lower with this technique. However, ECCE was cheaper and in lower income countries ECCE may therefore have a role in maximising the number of people that can be treated with limited resources.
We examined research published up to October 2019. We included studies which by chance decided whether people were asked to drink more water (to produce at least 2 litres of urine) or were given no special instructions. We found no studies of people who had never had kidney stones. We found one study, performed in 220 people who had calcium-containing stones in the past, but were stone-free when they started the study. The average age was approximately 41 years, and two-thirds of participants were men. We found that drinking more water may reduce the risk of stones coming back. It may also prolong the time it takes for stones to come back. We found no evidence of unwanted effects. The certainty of evidence for both outcomes for which we found evidence was low. This means that the true results may be quite different.
We included 38 studies (11,181 women), reporting three types of diagnoses from the frozen section test. 1. Cancer, which occurred in an average of 29% of women. 2. Borderline tumour, which occurred in 8% of women. 3. Benign mass. In a hypothetical group of 1000 patients where 290 have cancer and 80 have a borderline tumour, 261 women would receive a correct diagnosis of a cancer and 706 women would be correctly diagnosed without a cancer based on a frozen section result. However, 4 women would be incorrectly diagnosed as having a cancer where none existed (false positive), and 29 women with cancer would be missed and potentially need further treatment (false negative). If surgeons used a frozen section result of either a cancer or a borderline tumour to diagnose cancer, 280 women would be correctly diagnosed with a cancer and 635 women would be correctly diagnosed without a cancer. However, 75 women would be incorrectly diagnosed as having a cancer, and 10 women with cancer would be missed on the initial test and found to have a cancer after surgery. If the frozen section result reported the mass as benign or malignant, the final diagnosis would remain the same in, on average, 94% and 99% of the cases, respectively. In cases where the frozen section diagnosis was a borderline tumour, there is a chance that the final diagnosis would turn out to be a cancer in, on average, 21% of women. Where the frozen section diagnosis is a borderline tumour, the diagnosis is less accurate than for benign or malignant tumours. Surgeons may choose to perform additional surgery in this group of women at the time of their initial surgery in order to reduce the need for a second operation if the final diagnosis turns out to be a cancer, as it would on average in one out of five of these women.
This review examined whether providing iron supplementation is beneficial for preterm and low birth weight infants. The potential benefits included improvements in the level of red blood cells and stored iron in their blood. In the longer term, it was thought that iron supplementation might improve the babies' growth and development. We identified 25 randomised controlled trials (RCTs) which were relevant to this topic. We concluded that the long term benefits of iron supplementation for preterm and low birth weight babies remain uncertain. Regarding red blood cell and iron levels, it was found that in the first year of life, after two months of age, iron supplementation may result in slightly higher iron stores and red blood cell levels, and lower rates of iron deficiency anaemia. However, there was a lot of variability between different studies. More RCTs are needed, using well defined patient groups.
According to several studies RFA is technically feasible and safe for the treatment of CRLMs, however little is known about its efficacy in terms of overall survival (OS), disease free survival (DFS) and local recurrence. The aim of this review was to see if the treatment of CRLMs with RFA provides more benefit in terms of overall survival, disease free survival and local recurrence. This review include 18 studies (10 observational studies, 7 CCTs and an additional 1 RCT) comparing radiofrequency ablation with any other treatment. The heterogeneity regarding interventions, comparisons and outcomes rendered the data unusable and unsuitable for drawing conclusions. There is insufficient evidence to recommend the use of radiofrequency ablation for a radical treatment of liver metastases from colorectal cancer. High quality randomised clinical trials are required to answer on the potential benefit and harms associated with the use of radiofrequency ablation in the treatment of liver metastases from colorectal cancer.
Six randomised controlled studies of the effect of oxatomide were identified. All studies compared oxatomide with placebo. Two studies showed significant improvement with oxatomide as judged subjectively by the doctor. There was significant difference shown between oxatomide and placebo on objective outcomes (outcomes that are not influenced by people's opinions such as lung function or the amount of regular asthma medication taken by participants during the course of the study). Adverse effects were the only outcome able to be combined in a meta-analysis, and these were significantly more likely with oxatomide than with placebo treatment.
Three eligible studies with a total of 58 participants were included in this review. One study was conducted in the UK, one in Australia and one had multicentre sites in the UK and US. These studies varied significantly in interventions, methodology and reported outcomes. One study used 2% CsA in maize oil, and two used a commercial emulsion of 0.05% CsA. Of these three studies, two showed a beneficial effect of topical CsA in controlling signs of AKC, and one did not find evidence of this improvement. One study showed a beneficial effect of topical CsA in controlling symptoms of AKC, but the other two did not find evidence of this improvement. Only two studies analysed the effect of topical CsA in reducing topical steroid use; one showed a significant reduction in topical steroid use with CsA, but the other could not find evidence of this improvement. The data suggest that topical CsA may provide clinical and symptomatic relief in AKC and may help to reduce topical steroid use in patients with steroid-dependent or steroid-resistant AKC. Moreover, no serious adverse events were detected. However, this review has identified a need for more randomised controlled trials to provide further reliable evidence on the efficacy and safety of topical treatment with CsA eyedrops for patients with AKC. These trials should include larger samples of patients with AKC, and their follow-up periods should be long enough to draw conclusions on the long-term efficacy and safety of this therapy.
We included two trials for a total of 182 newborn infants comparing antithrombin with placebo (sugar or albumin solution). The use of antithrombin does not reduce the risks of bleeding in the brain, mortality or any other relevant outcomes in very preterm neonates when compared to placebo. However, the data collected are too limited to draw definitive conclusions on the use of antithrombin in the prevention of intraventricular hemorrhage (i.e. bleeding in the brain). The results of this systematic review are consistent with either a benefit or a detrimental effect of antithrombin and do not provide a definitive answer to the review question.
Injuries are the leading cause of childhood death in industrialised countries. People living in disadvantaged circumstances are at greater risk of injury than those who are more advantaged. This review examined whether home safety education and providing safety equipment reduced injuries and increased safety behaviours and safety equipment use. It also looked at whether home safety education was more or less effective in disadvantaged families. The review authors found 98 studies involving 2,605,044 participants which reported many different safety behaviours, but relatively few studies included information on injuries. The authors found that home safety interventions provided in the home may reduce injury rates, but more research is needed to confirm this finding. The results often varied between studies but, overall, families who received home safety interventions were more likely to have a safe hot tap water temperature, a working smoke alarm, a fire escape plan, fitted stair gates, socket covers on unused sockets, syrup of ipecac, poison control centre numbers accessible, and to store medicines and cleaning products out of reach of children. The authors found that home safety education was equally effective in the families whose children were at greater risk of injury.
The evidence is current to June 2014. The review included 18 studies with a total of 1250 women who had myomectomy for uterine fibroids. All studies compared an intervention to reduce bleeding during myomectomy with either a placebo or no such treatment. The data available suggest that vaginal insertion of misoprostol and infiltration of vasopressin into the uterine muscle are effective in reducing bleeding during myomectomy. Limited data available also suggest that chemical dissection (such as with mesna), vaginal insertion of dinoprostone, a gelatin-thrombin matrix, tranexamic acid, infusion of vitamin C (ascorbic acid) during surgery, infiltration of a mixture of bupivacaine and epinephrine into the uterine muscles, the use of fibrin sealant patch (a surgical patch that improves blood clotting) or a tourniquet around the cervix or around both the cervix and the infundibulopelvic ligamentmay be effective in reducing bleeding during myomectomy. We found limited information on the harms (adverse effects) of the different interventions. There is moderate-quality evidence that misoprostol reduces blood loss by between 70.24 ml and 125.52 ml; with a laparotomy vasopressin reduces blood loss by between 392.51 and 507.49 ml during myomectomy, and by between 121.73 ml and 172.17 ml during laparoscopic myomectomy. There is low-quality evidence for the rest of the interventions (chemical dissection, dinoprostone, gelatin-thrombin matrix, tranexamic acid, vitamin C, mixture of bupivacaine and epinephrine, a fibrin sealant patch and the two types of tourniquet).
We conducted a Cochrane systematic review of 53 well-designed experimental studies that examined the effectiveness of school-based universal programs for the prevention of alcohol misuse in young people. The studies were divided into two major groups based on the nature of the prevention program: 1) programs targeting specifically prevention or reduction of alcohol misuse and 2) generic programs with wider focus for prevention (e.g., other drug use/abuse, antisocial behavior). In the review we found studies that showed no effects of the preventive program, as well as studies that demonstrated statistically significant effects. There was no easily discernible pattern in program characteristics that would distinguish studies with positive results from those with no effects. Most commonly observed positive effects across programs were for drunkenness and binge drinking. In conclusion, current evidence suggests that certain generic psychosocial and developmental prevention programs can be effective and could be considered as policy and practice options. These include the Life Skills Training Program, the Unplugged program, and the Good Behaviour Game.
We looked for trials of oral protein calorie supplements compared to usual treatment or no alternative treatment where the children took the supplements for at least one month. The review included four trials with 187 children; in three of these the children had cystic fibrosis and in one they had cancer. Studies lasted from three months to one year. We recorded the results and judged whether the trials were at risk of being biased based on the design or the way it was run. We looked at outcomes such as weight and height, calorie intake, behaviour and also side effects. One study (with 58 children) showed increases in the total calories consumed at both six and 12 months. None of the other outcomes we looked at showed any difference between treatments. This is an updated version of the review, which found no conclusive evidence to support the use of oral protein supplements. We suggest that at least one high quality trial be conducted.Therefore, we suggest that these products are used sparingly and with caution. Overall the included studies had a low risk of bias, except for two studies in which it was possible that the organisers knew which treatment group in which the children would be placed. These issues are unlikely to change the results as knowing which treatment one receives is unlikely to affect the results of body measurements (e.g. weight, height outcomes). All planned outcomes were reported on, with the exception of one study that did not report on eating behaviour and lipase intake which were measured. The quality of the results for the eating behaviour assessment was questionable and many of the children did not return the food diaries from which the lipase intake could be calculated.
We carried out searches for studies that compared medical abortion (using pills) or surgical abortion provided by either mid-level providers or doctors. We also wrote to researchers to find more studies. The studies could compare how safe the abortions were or how effective they were (whether they actually worked). The evidence we found is up to date as of the 15th of August 2014. We found eight studies with a total of 22,018 participants. Five studies compared surgical abortion provided by doctors or mid-level providers and three studies compared medical abortion provided by doctors or mid-level providers. Of the five surgical abortion studies only one had a high-quality study design. Of the three medical abortion studies, two had a high-quality study design. Three of these studies were carried out in America, two in India, one in was carried out in both South Africa and Vietnam the remaining two were from Sweden and Nepal. The results from the analyses of the medical abortion studies showed that there does not seem to be an advantage when these are provided by doctors. The results from most of the analyses of the surgical abortion studies showed that we cannot be sure that there is a difference in how safe and how effective mid-level providers are compared to doctors. One analysis of three low-quality studies of surgical abortion showed that there was more chance of the abortion being ineffective if it was provided by mid-level providers. Most of the studies did not show a difference between mid-level providers and doctors in how safe the abortions were and how well they worked. Training mid-level providers to give medical or surgical abortions could reduce the number of deaths and the disability caused by unsafe abortion. Studies in the future should focus on what types of mid-level providers can provide safe and effective abortions. They should also look at whether mid-level providers are as safe and effective as doctors for providing abortions in rural developing country settings.
We included eight studies on preventive antibiotic therapy, with a total of 4488 people with stroke: 2230 participants were randomised to preventive antibiotic therapy, and 2258 to control. The mean age of participants in the preventive antibiotics group was 74.2 years, and in the control group 74.8 years. In both groups, the percentage of men was 52%. Study interventions differed in all eight studies; in two studies, trialists selected the (type of) antibiotic according to local antibiotic policy, with the aim of treating pneumonia. Preventive antibiotic treatment did not reduce the risk of dependency or death. However, preventive antibiotic therapy did significantly reduce the occurrence of 'overall' infections from 26% to 19%. Regarding type of infection, findings were highly significant for urinary tract infections (4% vs 10%) but showed no effect on pneumonia (10% vs 11%). No major side effects of preventive antibiotic therapy were reported. It has become possible to draw first 'overall' conclusions on the net effect of preventive antibiotic therapy in stroke; however, the decision of whether to use preventive antibiotic therapy in acute stroke should be reached with care. Studies were heterogeneous, and despite the large numbers of participants, results from a total of eight studies are limited. In two of these studies, risk of bias was considered to be high for three out of six criteria. Overall, reviewers considered the quality of evidence for the main outcomes of this review - looking at 'any' preventive antibiotic therapy, in 'any' dose, at any length of treatment - as high to moderate.
The evidence is current to 28 June 2019. We included 63 studies with 7768 adults who were undergoing heart surgery, including coronary artery bypass graft and valve replacement surgery. Studies were mostly randomized controlled studies, and six were quasi-randomized (participants were allocated to groups by methods such as using hospital record numbers or dates of birth). The types of beta-blockers were: propranolol, metoprolol, sotalol, esmolol, landiolol, acebutolol, timolol, carvedilol, nadolol, and atenolol. These beta-blockers were compared with either a placebo (disguised to look like a beta-blocker but containing no medicine) or with standard care. Beta-blockers were started before surgery, during surgery or at the latest by the end of the first day after surgery. The length of time beta-blockers were given varied between studies. In most studies, at least some of the people were already taking beta-blockers, which would be expected for people who had conditions that needed heart surgery. Key results Beta-blockers probably make little or no difference to the number of people who die (29 studies, 4099 participants) or have a heart attack (25 studies, 3946 participants) within 30 days of surgery. This was supported by low-certainty evidence. Few studies reported on people who had a stroke, and we were uncertain whether or not beta-blockers reduced strokes because the certainty of the evidence was very low (5 studies, 1471 participants). Beta-blockers may reduce atrial fibrillation, which is an irregular heartbeat starting in the atrial chambers of the heart that increases the risk of stroke if untreated (40 studies, 5650 participants; low-certainty evidence). Beta-blockers may also reduce ventricular arrhythmias, which are potentially life-threatening irregular heartbeat rhythms originating in the main chambers of the heart, and which may need immediate medical treatment (12 studies, 2296 participants). We found that beta-blockers may make little or no difference to whether people experience a very low heart rate or very low blood pressure. We were uncertain whether beta-blockers made a difference to the number of deaths up to a year after surgery (3 studies, 511 participants), to death because of the heart (4 studies, 320 participants), or to people who had heart failure (3 studies, 311 participants). The certainty of this evidence was very low. People who took beta-blockers had a shorter hospital stay by about half a day (14 studies, 2450 participants; low-certainty evidence). No studies assessed whether people on beta-blockers had a better quality of life after heart surgery. Certainty of the evidence The certainty of the evidence in this review was mostly low. We found that many studies reported methods that we believed could influence the results. For example, many studies did not use a placebo-control and the doctors might, therefore, have treated people differently in each group. We were unable to explain some of the differences that we found in the data for atrial fibrillation. We also needed to have evidence from a larger number of participants to be very confident in our findings. Conclusion Beta-blockers may be beneficial for people who are undergoing cardiac surgery because they may reduce the number of people who experience atrial fibrillation and ventricular arrhythmias. Beta-blockers may make little or no difference to the other outcomes in this review, including death, heart attacks or stroke.
We searched the literature up to 19 June 2015 and found four studies (N = 238 participants) for this review. The studies evaluated four different types of educational interventions, all targeting adolescents with different clinical conditions. All sought to improve knowledge and self-management skills of adolescents in preparation for transition to adult care. Three of the transitional-care programmes found that the intervention may slightly improve transitional readiness in young people, enabling them to better self-manage and adjust to using adult health services. One transitional-care programme that evaluated a two-day workshop for young people with spina bifida found little or no difference in measures of transitional readiness. Transitional-care programmes may slightly improve a young persons knowledge of their condition and their own appropriate use of health services. Transitional-care programmes led to little or no difference in health status, quality of life or well-being, or rates of transfer from child to adult health services. While there is a wide range of transition programmes that are being developed in different countries, often within particular clinical specialties, this review only identified four small studies that provided low certainty evidence about educational interventions targeting participating adolescents, and no studies of interventions that targeted the organisation of care (for example, joint clinics or provision of a key worker). Other limitations with the evidence are the small number of adolescents recruited, the limited number of clinical conditions studied, the short follow up (12 months or less), and the fact that only two of the included studies reported on the primary outcome (that is, condition-specific clinical outcomes). Despite the challenges in designing studies that can test these types of interventions, such as evaluating a complex intervention, a stronger evidence base is needed to inform the development of these services.
We included four trials in this review, comprising 245 participants, ranging in age from 22 to 92 years. Three trials measured physical activity outcomes after the treatment period. Trials were conducted in hospital and community settings. All participants were able to communicate and provide informed consent, and all were able to walk at least five steps without supervision or assistance. The experimental groups in the trials received feedback at least daily on the number of steps taken. We searched for studies up to 3 March 2018. We found that the use of wearable activity monitors to provide feedback on physical activity did not increase physical activity levels in people with stroke. No conclusions could be drawn regarding the influence of stroke severity, walking ability, stroke survivor age, or time poststroke on the outcomes. The four included studies were conducted in different settings, and used different outcome measures, which limited the ability to combine data. No study reported whether the use of physical activity monitors was harmful. More research is needed to determine if they are effective. Using the GRADE approach, the quality of the evidence was low to very low, due to the small number of studies, small sample sizes, and because no study was able to blind the participants or the therapists delivering the intervention (they were aware that a device was being used and aware of the feedback that was being provided by the device).
The evidence on which this review is based was up-to-date as of 16 April 2013. Nine studies were included in this review. A total of 366 adult participants took part in these trials, with an average of 40 participants per trial, and an age range from 12 to 77 years. The causes of dry mouth were radiotherapy for oral cancers in four trials, Sjögren's syndrome in three trials, medication-related in one trial, and in the remaining trial participants had a range of causes of dry mouth. The included studies were divided into three groups, according the interventions evaluated. 1. Five small studies with a total 153 participants evaluated acupuncture. 2. Three studies evaluated electrostimulation devices. 3. One study evaluated a power toothbrush. The five studies evaluating the effects of acupuncture in people who had dry mouth were generally of poor quality. There was no evidence of a difference in dry mouth symptoms, but there was some evidence of a small increase in saliva production which persisted for a year after the end of the acupuncture treatment. There may not have been enough people included in the trials to show a difference in dry mouth, or it may have been that both the real acupuncture and the 'placebo' acupuncture had some beneficial effect. Acupuncture was associated with more adverse effects (tiny bruises and tiredness which were mild and temporary). The studies evaluating the effects of electrostimulation devices were poorly conducted and reported, and provided insufficient evidence to determine the effects of these devices on either dry mouth or saliva production. The single small study of a powered versus a manual toothbrush also found no difference for either dry mouth or saliva production. None of the included studies reported the outcomes of duration of effectiveness, quality of life, patient satisfaction, or oral health assessment. These studies were generally of poor quality (low and very low).
This review included five studies in painful diabetic neuropathy (1863 participants) and one in fibromyalgia (159 participants). In people with painful diabetic neuropathy, lacosamide had only a modest effect, with a specific effect due to its use in 1 person in 10. This is a minor effect and may be an over-estimate due to use of the last observation carried forward method for analysis. There was insufficient information in fibromyalgia to draw any conclusions about the effect of lacosamide. There was no significant difference between lacosamide and placebo for participants with any, or a serious, adverse event, but there were significantly more adverse event withdrawals with lacosamide. Regulatory authorities have not licensed lacosamide for treating pain based on evidence presently available.
We included 14 studies that involved a total of 931 teenagers and adults. The studies investigated the effects of using laser irradiation provided by the orthodontist, vibratory devices, changing chewing patterns (patients chewing gum or wafers), brain wave music, cognitive behavioural therapy, and text messages to support people after braces were fitted. The main outcome measured was the intensity of pain over the short term as reported by patients. We found insufficient evidence to assess the effectiveness of the interventions, although the available low-quality evidence suggested that laser irradiation may help to control short-term orthodontic pain. None of the studies considered side effects of the treatments. We identified relatively few studies, some of which used flawed methods or were not well reported. More research to look at the possible merits of non-drug methods of pain control would be helpful. Future studies should measure pain over longer time periods and should measure side effects and costs. The quality of the evidence on the effectiveness of non-drug ways to ease orthodontic pain was low to very low, so we are not able to rely on the findings.
We searched the scientific literature for studies of anticoagulants in people with cancer. The evidence is current to 14 August 2017. We included 19 eligible trials. We selected 19 trials including 9650 participants with cancer. Most trials included participants with various types of cancer, especially small cell lung cancer, non-small cell lung cancer, and pancreatic cancer. All studies were conducted in the outpatient setting. The results suggest that the effect of injectable blood thinners on survival is uncertain, but if anything of small size. Also the results suggest that injectable blood thinners reduce the risk of blood clots by about half and possibly increase the risk of major bleeding and minor bleeding by 4 more per 1000 and 17 more per 1000, respectively. The effect on quality of life is uncertain. We judged the certainty of evidence to be high for symptomatic VTE and minor bleeding, and moderate for mortality, major bleeding and quality of life. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence, as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
The review found 16 trials which involved 1643 children. Most simple behavioural treatments were only studied in single small trials which makes the evidence less reliable. Simple treatments such as rewarding dry nights (e.g. with star charts), lifting and waking and bladder training appeared to be more effective than no treatment but they are not as effective when compared with other treatments known to work, such as enuresis alarm therapy and drug therapy. There does not appear to be one simple behavioural therapy that is more effective than another. On the other hand, simple treatments do not have any side effects or safety concerns. Therefore, simple methods could be tried as first line therapy before considering alarms or drugs for this common childhood condition.
We found 19 relevant studies involving 907 people. We were able to combine the results of 13 of these studies including 660 participants (395 traumatic brain injury, 234 stroke, 31 other acquired brain injury). Only two of the studies (82 people) reported the outcome in which we were most interested (a general measure of executive function). We found no evidence that cognitive rehabilitation interventions were helpful for people with executive dysfunction for any other outcomes. We recommend that more research is carried out to determine whether cognitive rehabilitation can improve executive function after stroke and brain injury.
We found six small trials of unclear quality answering these two questions. We found data from four trials on 171 children comparing anticholinergics with beta2-agonists. Children on anticholinergics alone were significantly more likely to experience treatment failure than those on beta2-agonists (odds ratio (OR) 2.27; 95% CI 1.08 to 4.75). We also found data from four trials on 173 children comparing children on anticholinergics alone with children on anticholinergics plus beta2-agonists. In this case, treatment failure was more likely in children taking anticholinergics only than if they were combined with beta2-agonists (OR 2.65; 95% CI 1.2 to 5.88). We were only able to combine data for treatment failure and hospitalisation. In summary, we found that inhaled anticholinergics used on their own are less effective than inhaled beta2-agonists used alone or in combination with anticholinergics. Inhaled anticholinergics seem safe, with no significant side effects apparent.
We searched medical databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) investigating male subfertility. We found 10 randomised controlled trials, all comparing different treatments for couples with male subfertility, with a total of 757 couples. The studies evaluated the following treatment options: timed intercourse (TI; where sex occurred at a recommended time in the menstrual cycle) (with or without OH), IUI (with or without OH), IVF and ICSI. The evidence was current to April 2015. We were mainly interested in how many women had live births and OHSS. We found no evidence of a difference in live birth or pregnancy rates between treatments. We also found no evidence of a difference between any of the groups in rates of adverse effects (multiple pregnancy, miscarriage). Available data on OHSS was too limited for us to draw any conclusions. Most of the evidence was of low or very low quality. The main limitations were failure to describe study methods, small sample sizes and inconsistency in how trials were conducted. Evidence was available for only six of the 14 comparisons that we evaluated. More research is needed.
In medical literature searches completed to January 2017, we identified and included one trial with 112 newborns comparing clonidine with placebo. We did not identify funding by industry for the included trial. Clonidine did not reduce death, duration of mechanical ventilation, or duration of stay in the intensive care unit. Sedation and pain scale values were lower among newborns receiving clonidine. Owing to the small number of newborns included in the single included trial, we are uncertain as to whether clonidine is effective or safe in providing analgesia and sedation for mechanically ventilated neonates.
Since there are several reviews describing the effects of different types of financial incentives, it is important to bring this together in an overview to examine which are best at changing healthcare professionals' behaviours and what happens to patients. We therefore conducted an overview of systematic reviews that evaluated the impact of financial incentives on healthcare professional behaviour and patient outcomes. We searched a wide range of electronic databases from when they started up to December 2008. We included systematic reviews of studies evaluating the effectiveness of any type of financial incentive. We grouped financial incentives into five groups: payment for working for a specified time period; payment for each service, episode or visit; payment for providing care for a patient or specific population; payment for providing a pre-specified level or providing a change in activity or quality of care; and mixed or other systems. We summarised data using vote counting. We identified four reviews reporting on 32 studies. Two reviews were of moderate quality and two were of high quality. The studies that the reviews reported on were of low to moderate quality. Payment for working for a specified time period was generally ineffective. Payment for each service, episode or visit was generally effective, as were payment for providing care for a patient or specific population and payment for providing a pre-specified level or providing a change in activity or quality of care; mixed and other systems were of mixed effectiveness. When looking at the effect of financial incentives overall across different outcomes, they were of mixed effectiveness on consultation or visit rates; generally effective in improving processes of care, referrals and admissions, and prescribing costs; and generally ineffective in improving compliance with guidelines outcomes. On the basis of these findings, we concluded that financial incentives may be effective in changing healthcare professional practice. The evidence has serious methodological limitations and is also very limited in its completeness and generalisability. We found no evidence that financial incentives can improve patient outcomes.
Nine studies were included in the review and evaluated eight different treatment modalities. In one small study of short duration (4 months), it was shown that the use of locally applied antibiotics in addition to the deep manual cleaning of the diseased implants decreased the depth of the pockets around the implants by an additional 0.6 mm in patients affected by severe forms of peri-implantitis. In another small study of 4-year duration, it was shown that placing an animal-derived bone substitute with a resorbable barrier decreased the depth of the pockets by an additional 1.4 mm than synthetic bone. The majority of trials testing more complex and expensive therapies did not show any statistically or clinically significant advantages over the deep mechanical cleaning around the affected implants. In conclusion, at present, there is too little evidence to determine which is the most effective way to treat peri-implantitis. This is not to say that currently used interventions are not effective.
We conducted a Cochrane systematic review of 20 randomised controlled trials that examined the effectiveness of universal multi-component programs for the prevention of alcohol misuse in young people. Multi-component prevention programs are defined as those prevention efforts that deliver interventions in multiple settings, for example in both school and family settings, typically combining school curricula with a parenting intervention. A majority of the studies included in this review reported positive effects of multi-component programs for the prevention of alcohol misuse in young people, with effects persisting into the medium- and longer-term. But a notable proportion of trials reported no statistically significant effects. In seven studies we were able to assess the impact of single versus multiple components, and only 1 out of the 7 studies clearly showed a benefit of components delivered in more than one setting. In conclusion, there is some evidence that multi-component interventions for alcohol misuse prevention in young people can be effective. However, there is little evidence that interventions with multiple components are more effective than interventions with single components.
For this updated review we found a total of 12 studies with 872 participants, most with high risk of bias. Four trials studied the efficacy of electrical stimulation (313 participants), three trials studied exercises (199 participants), and five studies combined some form of physical therapy and compared with acupuncture (360 participants). There is evidence from a single study of moderate quality that exercises are beneficial to people with chronic facial palsy when compared with controls and from another low quality study that it is possible that facial exercises could help to reduce synkinesis (a complication of Bell's palsy), and the time to recover. There is insufficient evidence to decide whether electrical stimulation works, to identify risks of these treatments or to assess whether the addition of acupuncture to facial exercises or other physical therapy could produce improvement. In conclusion, tailored facial exercises can help to improve facial function, mainly for people with moderate paralysis and chronic cases, and early facial exercise may reduce recovery time and long term paralysis in acute cases, but the evidence for this is of poor quality. More trials are needed to assess the effects of facial exercises and any risks.
This review examined the effectiveness of FP when given at different doses for treating asthma in children and adults. High doses (800 to 1000 microgram per day) led to small improvements in measures of airway opening compared to low doses (50 to 100 microgram per day) in people with mild to moderate asthma. High dose FP did not lead to clear improvements in symptoms over the lower dose and increased the risk of a hoarse voice and fungal mouth infections. In people with severe asthma, very high doses FP (2000 microgram per day) appeared to allow more people on oral steroids to stop or reduce their dose of oral steroid tablets compared to lower doses of FP (1000 to 1500 microgram per day).
We identified 21 studies that provided information on a total of 1676 people including 1628 adults and 48 children. The evidence was current to 30th September 2013. Studies were conducted in people with medical reasons such as pneumonia and other infections for needing admission to ICU, people admitted following trauma, and people admitted after heart or other forms of surgery. As well, various commercially available computerized weaning systems were studied. We found that computerized weaning systems resulted in a reduced weaning duration as well as reduced overall time on the ventilator and stay in an ICU. The average time required for a person to be weaned off the ventilator was reduced by 30%. The overall time on the ventilator was reduced by 10% and the length of stay in ICU by 8%. Not all studies demonstrated these reductions. Studies conducted only in people admitted to ICU following surgery did not demonstrate reductions in weaning, overall time on a ventilator or ICU stay. Because of differences in the methods and results of some studies included in this review, further large scale research is warranted. There is also a need for more studies that examine the effect of computerized weaning systems in children.
Twenty-six RCTs involving 3388 participants were identified. The majority of participants in all the studies were female (83% in the studies reporting sex distribution). The mean age was 40 years. The duration of follow up was between two to five years in eleven trials. In high dose ('block-replace') versus low dose ('titration') studies the duration of therapy was six months in two studies, 18 months in four studies and 12 months in the remaining trials. The main outcome was the relapse rate of hyperthyroidism over one year after completion of drug treatment and this was the primary outcome in all the studies assessed. There were no deaths reported in any of the studies. None of the studies detailed incidence of hypothyroidism, changes in weight during the course of therapy, health-related quality of life, ophthalmopathy progression or economic outcomes. The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the low dose regimen is 12 to 18 months. The low dose regimen had fewer adverse effects than the high dose regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. Studies using immunosuppressive agents need further validation of safety and efficacy in controlled trials among different populations. Data regarding side effects and number of participants withdrawn from therapy due to side effects were available in seven studies. The number of participants reporting rashes was significantly higher in the high versus low dose group (10% versus 6%). The number of participants withdrawing due to side effects were also significantly higher in the high versus low dose group (16% versus 9%).
We conducted a systematic review, comprehensively searching databases and other materials to identify randomised controlled trials which involved past or present consumers of mental health services employed as providers of mental healthcare services for adult clients. To be included, studies had to make one of two comparisons: 1) consumer-providers versus professionals employed to do the same role within a mental health service, or 2) mental health services with and without consumer-providers as an adjunct to the service. We found 11 randomised controlled trials involving approximately 2796 people. The quality of the evidence is moderate to low; it was unclear in many cases whether steps were taken to minimise bias, both in the way that participants were allocated to groups, and in how the outcomes were assessed and reported. Five of the 11 trials involving 581 people compared consumer-providers to professionals who occupied similar roles within mental health services (case management roles (4 trials), and facilitating group therapy (1 trial)). There were no significant differences between the two groups, in terms of client (care recipient) quality of life, mental health symptoms, satisfaction, use of mental health services, or on the numbers of people withdrawing from the study. People receiving care from past or present users of mental health services used crisis and emergency services slightly less than those receiving care from professional staff. Past or present consumers who provided mental health services did so differently than professionals; they spent more time face-to-face with clients, and less time in the office, on the telephone, with clients' friends and family, or at provider agencies. Six of the 11 trials, involving 2215 people, compared mental health services with or without the addition of consumer-providers. There were no significant differences in quality of life, empowerment, function and social relations, in client satisfaction, attendance rates, hospital use, or in the numbers of people withdrawing from the study, between groups with consumer-providers as an adjunct to professional care and those receiving usual care by health professionals alone. None of these six studies reported on clients' mental health symptoms. None of the studies reported on adverse outcomes (harms) for clients, or on the costs of providing the services. Overall, we concluded that employing past or present consumers of mental health services as providers of mental health services achieves psychosocial, mental health symptom and service use outcomes that are no better or worse than those achieved by professional staff in providing care. There is no evidence that the involvement of consumer-providers is harmful. More high-quality and well-reported randomised trials are needed, particularly to evaluate mental health outcomes, adverse outcomes for clients, the potential benefits and harms to the consumer-providers themselves (including a need to return to treatment), and whether it is cost-effective to employ them. Future researchers should include a clear description of the consumer-provider role and relevant training for the role so that it can be readily implemented, and should investigate consumer-providers in settings outside the United States.
This review found no evidence for routine use of opioids for newborns on breathing machines. Although relief of pain was variable, opioids were no better or worse for babies (in terms of death, strokes, future development, duration of ventilation or hospital stay) than other drugs or placebo. Further research is needed.
We included nine trials involving 1371 participants in the review. In general, no strong evidence was found to support the effectiveness of this approach, but it was shown to be effective in some contexts. In smoking cessation interventions the effect of showing and explaining artery scanning images (to assess the risk of cardiovascular disease) was found to be more effective than not communicating images. In other outcomes, the effects were mixed. There was no evidence of significant harmful effects of this approach, although this was not well reported. A main limitation of the review is the small number of studies in this area and the great differences between them in terms of the precise nature of the interventions and the populations being studied. This makes drawing broad conclusions difficult.
We found five randomised controlled trials (RCTs) that studied a total of 833 participants; one was a very small pilot study of seven participants. Four studies involved patients with AVGs; there was only one study of AVFs. The outcomes were measured over a period of six or 12 months. There were reservations about the overall quality of all the studies, making us moderately to highly uncertain about the evidence. In AVF patients, we are moderately certain that fish oil supplements do not prevent blockage nor do they cause additional harm but the evidence only comes from one study. In AVG patients, we are very uncertain of the evidence for preventing blockage or causing serious harm, but there may be an increased risk of mild digestive side-effects such as a sensation of bloatedness, gas or a fishy aftertaste. There is limited high quality data on the benefits of omega-3 fish oil supplementation for preventing HD blockage in kidney failure patients. We did not find strong evidence that omega-3 fish oil supplements could prevent blockage of HD vascular access or that it increases the risk of serious and non-serious side-effects. All the evidence for preventing blockages come from just one or two studies, so more and better quality studies are needed.
The review authors searched the medical literature up to 7 January 2014, and identified seven relevant medical trials, with a total of 403 participants. Six trials compared the use of phototherapy with standard care only; one trial compared it with standard care plus sham phototherapy. Only one trial included a third treatment group that investigated another type of phototherapy. Two trials reported the time taken for pressure ulcers to heal completely, and these showed an improvement in healing time for people in the phototherapy group who received treatment with ultraviolet light. However, this result should be interpreted with caution, as these were small, poor quality trials, at unclear risk of bias (i.e. with potentially misleading results), and the findings may have been due to chance. The other trials reported either conflicting results or various measures/time points among trials, which meant that we could not conclude whether or not phototherapy is effective for treating pressure ulcers. Two trials reported incidence of harmful (adverse) effects and noted no significant differences between the phototherapy and standard treatment groups. Four trials provided funding information, two from industry funding, the others from an institutional grant. No studies reported on quality of life, length of hospital stay, pain or cost. This review identified only a few, small studies provided with insufficient evidence to support the use of phototherapy as a routine treatment for pressure ulcers. More trials will need to be conducted before it can be established whether this treatment works and is safe.
The review included five studies with a total of 386 people with sickle cell disease aged between four and 53 years. Two studies (306 people) compared intravenous magnesium to a placebo (in this case saline (salty water)) in people admitted to hospital as an emergency because of pain and lasted until they were discharged (less than four weeks). Two of the three longer-term studies compared oral magnesium pidolate with placebo and the third study compared hydroxyurea and magnesium pidolate to each other and to placebo but we have only included the results of the comparison of magnesium pidolate to placebo). Not all the studies reported on our outcomes and we could not analyse data from most of the studies. We did find that in the people admitted to hospital as emergency cases, intravenous magnesium did not reduce pain levels, could not shorten the length of time spent in hospital and did not improve their quality of life compared to placebo. However, more people given magnesium experienced warmth where the needle was inserted than those people who were given placebo. Oral magnesium pidolate, given over a longer period, did not reduce the severity of painful episodes and had no measurable effect on properties of sickled red cells (e.g. magnesium levels in the blood). Oral magnesium appeared to be safe and well-tolerated with only mild side effects (diarrhoea and headache). Further research is needed to compare the short-term and long-term benefits of magnesium treatment and its side effects. The quality of evidence for intravenous magnesium and oral magnesium in treating sickle cell disease was moderate for pain when using short-term intravenous magnesium and for levels of magnesium in the blood when taking longer-term oral magnesium supplements. The quality of evidence was low for all other outcomes we measured. All of the included studies of oral or intravenous magnesium for treating sickle cell disease had some aspects that could undermine the reliability of their results. Therefore, we have some uncertainty of these findings and further research may provide evidence that could change our conclusions.
The purpose of this review was to assess how effective cyclobenzaprine is at reducing pain and improving sleep in patients with MP. We searched extensively through scientific publications and found two trials, with a total of 79 participants. These tested cyclobenzaprine against another drug called clonazepam, and fake medication (placebo), or against injections of a local anesthetic called lidocaine. A total of 35 of the 79 participants in the two trials were given cyclobenzaprine. Cyclobenzaprine was slightly better than clonazepam and placebo at reducing jaw pain, but was no better at improving sleep quality. The results from the other trial were not scientifically reliable because of the small number of participants involved, but lidocaine injections seemed to reduce pain slightly better than cyclobenzaprine pills. Despite this result, it is likely that, because it is uncomfortable to receive any form of injection, people who suffer from MP will prefer to be treated with cyclobenzaprine pills. There were no life-threatening adverse events associated with any of the medications studied. Further studies are needed to show whether cyclobenzaprine really works for treating MP, but at the moment doctors cannot say whether it is really useful.
The review author searched the medical literature to find out if aminosteroids help people with traumatic brain injury when given within seven days of the injury. The author looked for randomised controlled trials in which one group of patients received a treatment (aminosteroids) while a similar group received non-active treatment (placebo) in addition to standard care. To reduce possible bias, each patient is randomly assigned to a group. The author found two such studies, which used the aminosteroid tirilazad mesylate, but the results of one of the studies were not available at the time of review. The completed study involved 1131 patients. The results of this study showed no benefit from the aminosteroid. The aminosteroid group did not have more side effects than the placebo group but aminosteroids are fairly new drugs that may have unknown less common side effects. More research is needed on the use of aminosteroids to treat traumatic brain injury but currently there is no evidence to recommend their use.
The researchers identified three studies that included a total of 165 patients. One study (67 patients) compared oral methotrexate (12.5 mg/week) to placebo (e.g. a sugar pill or fake medicine), one study (26 patients) compared oral methotrexate (15 mg/week) and sulfasalazine (3 g/day) to sulfasalazine alone, and one study (72 patients in total; of which, 34 had ulcerative colitis ) compared oral methotrexate (15 mg/week) to 6-mercaptopurine (1.5 mg/kg/day) or 5-aminosalicylic acid (3 g/day). Two studies were judged to be of very low quality and the placebo-controlled study was judged to be of high quality. There was no difference between the methotrexate and placebo treatment groups for the number of people who maintained remission at nine months. This suggests that, when used at this low dose (12.5 mg/week) methotrexate does not maintain remission in patients with inactive ulcerative colitis. However, this result is uncertain due to the small number of people who were assessed There was no difference between the combination therapy (methotrexate plus sulfasalazine) and sulfasalazine treatment groups for the number of people who maintained remission at 12 months. This result is uncertain due to poor study design and the low number of participants. The other, small study showed no differences between methotrexate and the other treatments (6-mercaptopurine and 5-aminosalicylic acid) in the proportion of participants who were able to maintain remission. These results are uncertain due to poor study design and the low number of participants. The side effects reported in the studies included leucopenia (a decrease in the number of white blood cells), migraine, rash, nausea and dyspepsia (indigestion), mild alopecia (hair loss), mild increase in levels of an enzyme found in the liver (aspartate aminotransferase), a collection of pus in the abdominal tissue (peritoneal abscess), abnormally low levels of the protein albumin in the blood (hypoalbuminemia), and pneumonia. At present, the results from medical trials do not support the use of low dose oral methotrexate (12.5 mg to 15 mg/week) for maintenance of remission in people with inactive ulcerative colitis. It is not known whether a higher dose of oral methotrexate, or giving methotrexate by a different route (e.g. by injection), would be effective for maintenance of remission in people with inactive ulcerative colitis. In future, researchers should consider organizing a study with a larger number of participants who receive a higher dose of methotrexate (15 to 25 mg/week). Future studies should also investigate methotrexate given by injection. The results of such studies may resolve the uncertainty surrounding the use of methotrexate as maintenance therapy in people with inactive ulcerative colitis.
We included two randomized studies, in six published reports, with 431 participants with locally advanced esophageal cancer. We searched biomedical databases, clinical trial registries, conference proceedings, and reference lists up to 7 February 2017 for studies. The quality of evidence ranged from very low to high, depending on the outcome being assessed, because the trials were small and at unclear or high risk of bias (a systematic error or deviation from the truth that affects the results, favouring one treatment over another). We found evidence that adding surgery reduced the risk of the cancer recurring at the primary site, but did not improve overall survival. Moreover, there were more treatment-related deaths in the group of participants who underwent surgery.
This review includes three randomised controlled trials with a total of 131 participants and two of them only included children. Two of the trials compared supplements to dietary advice and one compared supplements to no advice. The trials lasted between three months and one year. Key results There were no major differences between people receiving supplements or just dietary advice for any nutritional or growth measurements. This was also true for measures of body composition, lung function, adverse effects on the digestive system or people's levels of activity. Advice and monitoring appear to be enough to manage the diet of moderately malnourished children. Future trials should look into the use of calorie supplements for acute weight loss or long-term care for adults with cystic fibrosis. Quality of the evidence One of the trials appeared to be well run and the risk of bias was low for all the aspects of trial design that we assessed; so we do not think any bias will influence the results in a negative way. In the other two trials, we were not sure if the people taking part could guess which treatment group they were in. In one of these two trials, we further thought it was likely that the person recruiting them to the trial knew which group the participant would be in. In the second of these trials, the people in the group receiving supplements appeared to be generally in better clinical condition at the start of the trial than those who didn't receive any supplements or advice. These factors affect our confidence in the results from these trials. We judged the quality of the evidence for the changes in weight and height to be moderate, but judged the quality of the evidence for the changes in total calories, total fat and total protein intake as low since results are applicable only to children aged between 2 and 15 years; also many post-treatment diet diaries were not returned to the investigators. Evidence for the rate of adverse events in the treatment groups was extremely limited and judged to be of very low quality.
We conducted our most recent search for studies in March 2018 and combined with an earlier search selected 29 clinical studies reporting the evaluation of PCR tests prospectively in cohorts of people at high risk of IA. None of the companies involved in the diagnosis of invasive fungal diseases funded any of the studies included in the review. Most studies were at low risk of bias and low concern regarding applicability. However, differences in the reference standard may have contributed to differences we found in the distribution of cases as being classified as IA or not. Several PCR techniques were used in the studies. Pooling the data from the studies showed that sensitivity and specificity of PCR for the diagnosis of IA varied (from 59% to 79.2% and from 79% to 95.2%, respectively) depending on the interpretative criteria used to define a test as positive. When used as a diagnostic criterion for IA in a population of 100 people with a disease prevalence of 16.3% (overall mean prevalence), a single PCR positive test would have missed three people with the disease, and falsely classified 17 people as having the disease, who would be treated unnecessarily or referred for further tests. A requirement of two positive tests as a diagnostic criterion in a population with the same disease prevalence would miss nine people with the disease and falsely classify four people as having the disease. These numbers should be interpreted with caution because the reference standard is based on the degree of certainty of diagnosis and is rarely proven so cannot provide consistent assessment of cases as being IA or not. Overall, PCR shows moderate diagnostic accuracy when used as a screening test for IA in high-risk patient groups. Importantly, when the rate of sensitivity is low, the sensitivity of the tests means that a negative result allows the diagnosis to be excluded with confidence except when the patient is receiving certain antifungal drugs. With the low prevalence of the disease, a high negative predictive value such that a negative test allows the diagnosis to be excluded.
The authors of this study reviewed the medical literature to ascertain the best antibiotic combination for the treatment of this condition. Four eligible studies were identified and only two of these studies were found to be suitable for analysis. Both these studies were performed before 1988. The two studies included 62 infants with NEC and compared one antibiotic regimen to another. There was no difference between the two groups. The authors concluded that there was insufficient evidence to recommend a particular antibiotic regimen for NEC.
Evidence from this review of 10 trials involving 1967 patients undergoing 2157 operations now suggests a benefit from using routine patch angioplasty during carotid endarterectomy. About 20% of strokes result from narrowing of the carotid artery (the main artery supplying blood to the brain). Carotid endarterectomy is an operation that involves opening the carotid artery to remove this narrowing and, therefore, reduce the risk of stroke. However, there is a 2% to 10% risk of the operation itself causing a stroke. Some surgeons advocate the incorporation of a patch made out of either synthetic material or the patient's own vein, into the arterial closure. This may help to reduce the risk of the artery being narrowed during suture placement and may, therefore, reduce the risk of recurrent blockage and consequent stroke or death or both. However, use of a patch may increase surgical difficulty and operation length. Furthermore, thin-walled vein patches may rupture with potentially fatal consequences and synthetic materials are vulnerable to infection.
An updated search for relevant randomised controlled trials was run in October 2014, and again, in December 2016 and found one new study. Five studies have now been found that meet the review inclusion criteria. The included studies are all randomised, and investigate the effects of giving different doses of chlorpromazine to people with schizophrenia. The total number of participants was 585. Chlorpromazine showed different effects at varying doses. Based on weak evidence, the effects on people’s mental health at low dosage and medium dosage are much the same. However, there are more side effects at medium dose. There is more improvement in people’s mental health at high dose compared to low dose. However, side effects are much more numerous and debilitating at high dose. In the past fifty years, low dose has been the favoured amount to use with patients. This change has come about gradually and is based on everyday experience and consensus rather than hard scientific evidence. Chlorpromazine is low-cost and widely available. Despite its many side effects, chlorpromazine is likely to remain a benchmark or ‘gold standard’ drug and one of the most widely used treatments for schizophrenia worldwide. All trials in the review are hospital- based and all but one date from 20 years ago. There are a limited number of studies of limited quality and these are poorly reported and short term. Further research and trials on chlorpromazine dose are justified. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/
This review sets on to determine the efficacy and adverse events of different neoadjuvant therapies (drug given before) versus adjuvant therapies (drug given after) compared to surgery alone, or surgery and placebo or supportive therapy when given to improve relapse and survival rates for operable hepatocellular carcinoma. A total of 12 randomised trials were identified, totaling 843 patients. The size of the randomised clinical trials ranged from 30 to 155 patients. Nine of the twelve trials reported no survival benefit from adjuvant therapy. Two trials reported a significant difference for survival and four studies for disease-free survival for the treatment group, but the results of one of the trials on both its groups were very poor when compared to other trials. Two of the trials that did not report any absolute survival advantage reported statistically significant differences in disease-free survival. The highest toxicity rate was in a trial using oral 1-hexylcarbamoyl 5- fluorouracil which resulted in 12 out of 38 patients being withdrawn from the trial because of adverse events. In conclusion, this review found insufficient evidence to show that adjuvant and neo-adjuvant therapy increase survival from hepatocellular carcinoma, but there is limited evidence to suggest that neoadjuvant or adjuvant therapy may be useful for disease-free survival.
We searched for evidence in April 2017 and found two randomised controlled trials, conducted in outpatient departments of the same two hospitals in the USA, between 1993 and 2001. One trial was sponsored by a drug company. The trials randomised a total of 514 pregnant women (347 women analysed), at an average gestational age of 22 weeks. Both trials had a follow-up of 14 days. We were unable to pool the results because the trials used different comparisons. One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral), and the other trial assessed a higher dose of ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include data from the spectinomycin group because this medication is no longer produced. We found no clear difference in the rate of cure of gonococcal infection (both genital and unrelated to the genital organs) for the different treatment groups, which was in the order of 89% to 96% (very low-quality evidence). Trials did not report on the incidence of obstetric complications, disseminated gonococcal infection in the mother, or ophthalmia neonatorum in the baby. They provided little information on side effects of the antibiotic regimens. One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not report numbers or severity. Hyperberbilurrubinemia (where the baby has too much bilirubin in the blood) was more frequent in newborns whose mothers were exposed to ceftriaxone. There was no clear difference between groups for neonatal malformation. We found high levels of cure of gonococcal infection in pregnancy with the given antibiotic regimens, but here was not enough evidence to support one particular regimen over another. Despite high levels of cure, our confidence in the results of this review is very low because both included trials were small, did not blind women to which treatment they received, and had a high number of withdrawals (28% and 41%), meaning they were at high risk of bias. Therefore, there is a need for high-quality trials to be conducted to assess the clinical effectiveness and potential harms of antibiotics for treating gonorrhoea in pregnancy women.
In this review of randomized controlled trials, a commercially available inactivated vaccine given in two doses was shown to provide disease protection for at least one year after vaccination, but with some adverse events. Disease protection by two vaccines, widely used in China but presently commercially unavailable, has not been investigated in randomized controlled trials. Further research is needed on all currently used as well as newly developed vaccines.
We found 22 research studies involving 695 participants, which reported on the efficacy of interventions related to theory of mind. The evidence is current to 7th August 2013. Despite all studies using a high-quality basic methodology (the randomised controlled trial), there was concern over poor study design and reporting in some aspects. While there is some evidence that theory of mind, or related skills, can be taught to people with ASD, there is currently poor quality  evidence that these skills can be maintained, generalised to other settings, or that teaching theory of mind has an impact on developmentally-linked abilities. For example, it was rare for a taught skill to generalise to a new context, such as sharing attention with a new adult who was not the therapist during the intervention. New skills were not necessarily maintained over time. This evidence could imply that the theory of mind model has little relevance for educational and clinical practice in ASD. Further research using longitudinal methods, better outcome measures, and higher standards of reporting is needed to throw light on the issues. This is particularly important as the specific details of the theory of mind model continue to evolve.
We searched the scientific literature for randomised controlled trials (experiments that randomly allocate participants to one of two or more treatment groups) looking at the effectiveness of exercise-based treatments compared with no exercise in people of all ages with CHD. The search is current to July 2014. This latest update identified 16 trials (3872 participants). We included a total of 63 trials that studied 14,486 people with CHD, predominantly heart attack survivors and those who had undergone heart bypass surgery or angioplasty (a procedure which widens narrowed or obstructed arteries or veins). The findings of this update are consistent with the previous (2011) version of this Cochrane review and show important benefits of exercise-based cardiac rehabilitation that include a reduction in the risk of death due to a cardiovascular cause and hospital admission and improvements in health-related quality of life, compared with not undertaking exercise. There was a considerable variation across studies in the reporting of health-related quality of life outcome. A small body of economic evidence was identified indicating exercise-based cardiac rehabilitation to be cost-effective. Further evidence is needed to understand the effect of exercise training in people with CHD who are higher risk and in those with established angina (chest pain). Although the reporting of methods has improved in recent trials, lack of reporting made it difficult to assess the overall methodological quality and risk of possible bias of the evidence.
The review identified two randomised controlled trials of aromatherapy. One trial involving 513 women compared one of Roman chamomile, clary sage, frankincense, lavender or mandarin essentials oils with standard care. The aromatherapy was applied using acupressure points, taper, compress, footbath, massage or a birthing pool. The second trial involved 22 women randomised to bathe for at least an hour in water with either essential oil of ginger or lemongrass added. All women received routine care and had access to pain relief. The trials found no difference between groups for pain intensity, assisted vaginal birth, caesarean section or the use of pharmacological pain relief (epidural). Overall, there is insufficient evidence from randomised controlled trials about the benefits of aromatherapy on pain management in labour. More research is needed.
Foot ulcers not only lead to physical disability and loss of quality of life, but also to economic burden (healthcare costs, industrial disability). The aim is therefore to prevent foot ulcers occurring, for example, by showing patients with diabetes how to look after their feet or by prompting doctors to check their patients' feet more often. The results of single prevention strategies alone have so far been disappointing, therefore in clinical practice, preventive interventions directed at patients, healthcare providers and/or the structure of health care are often combined. In this review of trials of complex, preventive interventions, we found insufficient evidence that these combined approaches can be effective in reducing foot problems.
In the present review we assessed the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with all other antidepressants in the acute-phase treatment of major depression. Fifty-nine randomised controlled trials (about 10,000 participants) were included in the review. The review showed evidence of differences in efficacy, acceptability and tolerability between sertraline and other antidepressants, with meta-analyses highlighting a trend in favour of sertraline over other antidepressants, both in terms of efficacy and acceptability, in a homogeneous sample of clinical trials, using conservative statistical methods. The included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians, in particular, patients and their carers' attitudes to treatment, their ability to return to work and resume normal social functioning, were not reported in the included studies. Nevertheless, based on currently available evidence, results from this review suggest that sertraline might be a strong candidate as the initial choice of antidepressant in people with acute major depression.
This updated review included 16 new studies involving 25,819 participants, resulting in a total of 42 studies including 33,840 with stroke or TIA whose average age ranged from 60 to 74.3 years. Most studies took place in primary care or community settings. Sixteen studies involved educational or behavioural interventions for participants and 26 studies mostly involved organisational interventions. Most interventions lasted for between three and 12 months, with follow-up from three months up to three years. Changes to healthcare services that looked at patient education or behaviour only, without any alterations in the organisation of patient care, showed no clear evidence of improvements in risk factors for stroke. Changes in the organisation of healthcare services resulted in improvements in blood pressure control. The effects of these interventions on changes in blood fats, blood sugar, body weight, or use of medicines were not conclusive. We identified 24 ongoing studies suggesting that research in this area is increasing. The available evidence was assessed as moderate- or low-quality because of variations in methods used and results reported.
We examined the scientific literature up to May 2015. We identified six randomised controlled trials (studies where people were allocated at random to one of two or more treatment or control conditions) involving 607 people who were dependent on pharmaceutical opioids. The people in the study were 77% male and had an average age of 31.6 years. The average duration of the studies comparing different opioid maintenance treatments (three studies that compared methadone to buprenorphine) was 24 weeks, and the average duration of studies comparing a maintenance treatment (three studies with buprenorphine maintenance) to detoxification or psychological treatment was 10 weeks. Five of the six studies were conducted in the US, with one study from Iran. We looked at opioid use and leaving treatment early. Five of the studies were funded by the National Institute of Health (USA), with one study not reporting the funding source. Four studies reported that a drug company provided the medicine. We found that there is probably little or no difference between how well methadone and buprenorphine worked to keep people in treatment, to reduce opioid use, or side effects. We found that buprenorphine probably keeps more people in treatment, may reduce use of opioids, and has fewer side effects compared to detoxification or psychological treatment alone. Overall, the evidence was of low to moderate quality. All studies put people into treatment groups randomly, but the participants and researchers knew which medication the participants were taking, which could bias the results and lower the quality of the evidence. Some of the studies had reasonable numbers of people who did not finish the study in both treatment groups, which means there are some missing results, but the number of people with missing results was similar in both treatment groups of the study for most studies. Most of the studies were similar in design and results were collected in a way that allowed them to compare opioid use and number of people completing the study.
Cochrane Schizophrenia's Information Specialist ran an electronic search in January 2016, searching their specialised register for trials that randomised people with schizophrenia to receive either chlorpromazine or clotiapine. The search identified six reports. We inspected these reports and found four trials, published between 1974 and 2003, randomising 276 participants that could be included in the review. The four included trials were poorly conducted and did not report data for clinically important change in global or mental state, or cost of care. Improvement in overall mental state was reported and participants receiving clotiapine had better improvement scores than those receiving chlorpromazine. However the trials also reported data for improvement in the negative symptoms, no difference between the two treatments was found. Clotiapine did not cause more movement disorders than chlorpromazine, and similar numbers of participants left the trials early. There is some very low-quality evidence that favours clotiapine over chlorpromazine for improving overall mental state. For other outcomes, including adverse effects, there is no evidence of a difference between these two antipsychotics. However these data are very difficult to draw conclusions from, only four small trials provided data and these were poorly conducted. We cannot draw conclusions on the comparative effectiveness of chlorpromazine versus clotiapine from such data.
This review summarises trials evaluating the effects of dihydroartemisinin-piperaquine (DHA-P) compared to other artemisinin-based combination therapies recommended by the World Health Organization. After searching for relevant trials up to July 2013, we included 27 randomized controlled trials, enrolling 16,382 adults and children and conducted between 2002 and 2010. What is uncomplicated malaria and how might dihydroartemisinin-piperaquine work Uncomplicated malaria is the mild form of malaria which usually causes a fever, with or without headache, tiredness, muscle pains, abdominal pains, nausea, and vomiting. If left untreated, uncomplicated malaria can develop into severe malaria with kidney failure, breathing difficulties, fitting, unconsciousness, and eventually death. DHA-P is one of five artemisinin-based combination therapies the World Health Organization currently recommends to treat malaria. These combinations contain an artemisinin component (such as dihydroartemisinin) which works very quickly to clear the malaria parasite from the person's blood, and a longer acting drug (such as piperaquine) which clears the remaining parasites from the blood and may prevent new infections with malaria for several weeks. What the research says DHA-P versus artemether lumefantrine In studies of people living in Africa, both DHA-P and artemether-lumefantrine are very effective at treating malaria (high quality evidence). However, DHA-P cures slightly more patients than artemether-lumefantrine, and it also prevents further malaria infections for longer after treatment (high quality evidence). DHA-P and artemether-lumefantrine probably have similar side effects (moderate quality evidence). DHA-P versus artesunate plus mefloquine In studies of people living in Asia, DHA-P is as effective as artesunate plus mefloquine at treating malaria (moderate quality evidence). Artesunate plus mefloquine probably causes more nausea, vomiting, dizziness, sleeplessness, and palpitations than DHA-P (moderate quality evidence). Overall, in some people, DHA-P has been seen to cause short term changes in electrocardiographs tracing the conduction of the heart rhythm (low quality evidence), but these small changes on the electrocardiograph resolved within one week without serious consequences.
We found 43 studies including more than 30,000 people with COPD. More studies used fluticasone (26 studies; 21,247 people) than budesonide (17 studies; 10,150 people). A higher proportion of people in the studies were male (around 70%), and their COPD was generally classed as severe. The last search for studies to include in the review was done in September 2013. We compared each drug against controls and assessed separately the results of studies that compared ICS versus placebo, and an ICS/LABA combination versus LABA alone. We also conducted an indirect comparison of budesonide and fluticasone based on their effects against placebo, to explore whether one drug was safer than the other. Fluticasone increased 'serious' pneumonias (requiring hospital admission). Over 18 months, 18 more people of every 1000 treated with fluticasone were admitted to hospital for pneumonia. Budesonide also increased pneumonias that were classed as 'serious'. Over nine months, six more hospital admissions were reported for every 1000 individuals treated with budesonide. A lower dose of budesonide (320 mcg) was associated with fewer serious pneumonias than a higher dose (640 mcg). No more deaths overall were reported in the ICS groups compared with controls, and deaths related to pneumonia were too rare to tell either way. When we compared fluticasone and budesonide versus each other, the difference between them was not clear enough to tell whether one was safer (for pneumonia, requiring a hospital stay, general adverse events and death). The risk of any pneumonia event (i.e. less serious cases that could be treated without going to hospital) was higher with fluticasone than with budesonide. Evidence was rated to be of high or moderate quality for most outcomes. When an outcome is rated of high quality, further research is very unlikely to change our confidence in the estimate of effect, but moderate ratings reflect some uncertainty in the findings. Results from the budesonide studies were generally less clear because they were based on fewer people, and the studies were shorter. Budesonide and fluticasone, delivered alone or in combination with LABA, can increase serious pneumonias that result in hospitalisation of people. Neither has been shown to affect the chance of dying compared with not taking ICS. Comparison of the two drugs revealed no difference in serious pneumonias or risk of death. Fluticasone was associated with a higher risk of any pneumonia (i.e. cases that could be treated in the community) than budesonide, but potential differences in the definition used by the respective drug manufacturers reduced our confidence in this finding. These concerns need to be balanced with the known benefits of ICS (e.g. fewer exacerbations, improved lung function and quality of life). Researchers should remain aware of the risks associated with ICS and should make sure that pneumonia is properly diagnosed in studies.
Four studies with a total of 136 participants were included. Two studies compared the use of plugs versus no plugs. The involuntary loss of stool was effectively blocked (pseudo-continence) in six (38%) participants who continued to use the plugs, at least in the short-term. One study compared two sizes of the same brand of plug; due to the high dropout in this study and the incomplete data, no results concerning this comparison are available. In one study a comparison of two different brands of plug was made. Loss of plug was reported by 7 patients (30%) with a polyurethane (PU) plug and by 15 patients (65%) with the polyvinyl-alcohol (PVA) plug. Overall satisfaction, defined as patients' opinion that the plug was good to very good, was reported more often for the PU plug (n = 17) than for the PVA plug (n = 8). In all included studies there was considerable dropout; in total 48 participants (35%) dropped out before the end of the study for varying reasons. Data presented are thus subject to potential bias, and only tentative conclusions are possible. The available data suggest that anal plugs can be difficult to tolerate. However, if they are tolerated they can be helpful in preventing incontinence. Plugs could then be useful in a selected group of people either as a substitute for other forms of management or as an adjuvant treatment option. Plugs come in different designs and sizes; the review showed that the selection of the type of plug can impact on its performance.
This review is based on 16 studies (1565 participants) that tried out different methods to help people to use drops as prescribed. All the studies took place in industrialised countries (Belgium, Denmark, France, Greece, Iceland, Japan, Sweden, Switzerland, UK and USA) and recruited participants in outpatient clinics. The following interventions were included: simplifying drop routines, reminder devices, automated telephone service, providing information about glaucoma and offering advice regarding day to day issues with eye care. Those studies which combined the provision of information about glaucoma and eye drops with other interventions, such as helping people to fit instillation of eye drops into their daily routine, appear to be more successful. Unfortunately, not all of these studies were of high quality and, therefore, until more evidence is available we cannot recommend any particular method. Good quality research is needed in this area in order to develop a better understanding of patients' individual needs and to help us provide more effective eye care services.
Twelve trials (1241 patients) assessing several antibiotic prophylaxis regimens versus no intervention or placebo were analysed, showing that antibiotic prophylaxis successfully reduced the incidence of bacterial infections. Antibiotic prophylaxis was also associated with a reduction in mortality, mortality from bacterial infections, rebleeding rate, and days of hospitalisation. The prophylactic treatment was not associated with important adverse effects. Five trials (650 patients) assessed one antibiotic regimen compared with another. All antibiotic regimens provided similar benefits and none seemed superior. Thus, to this point there is no evidence to recommend one specific antibiotic regimen over the other. All trials analysed were subject to bias; thus, results should be interpreted carefully.
This Cochrane Review is current to July 2018. We searched online databases for all studies (specifically randomised controlled trials) that compared surgical treatment with non-operative treatment in adults with patellar tendinopathy. We found two studies; they compared open surgical removal to eccentric exercises (one study involving 40 people) and arthroscopic surgery to sclerosing injections (these scar and block the blood vessels supplying nerve fibres to the diseased tendon) (one study involving 56 people). The studies were performed in an outpatient setting in two countries (Norway and Sweden). The majority of people in the studies were male, with a mean age ranging from 27 to 31 years, and mean symptom duration of 24 to 33 months. Trials were conducted without funding (financial support) from industry (medical or device companies), but some authors from the one study received funding from pharmaceutical companies in addition to research funding from non-industry sources. Compared with eccentric exercises, open surgery offered little benefit at 12 months (results for individual outcomes as follows). Pain (lower scores mean less pain) Improved by 4% (ranging from 4% worse to 12% better) or by 0.4 points on a scale of zero to 10 points. People who had surgery rated their pain as 1.3 points. People who had eccentric exercises rated their pain as 1.7 points. Global assessment of success (those who reported no pain at 12 months) 10% fewer people had no pain (ranging from 38% less to 18% more), or 10 fewer people out of 100. Twenty-five out of 100 people had no pain with surgery. Thirty-five out of 100 people had no pain with eccentric exercises. Withdrawals No participants in either group withdrew from the study. The study did not report on quality-of-life improvements or adverse events (including tendon ruptures). Compared with sclerosing injections, arthroscopic (keyhole) surgery offered some reduction in pain and improvement in participant global assessment of success at 12 months (results for individual outcomes as follows; further studies are likely to change these results). Pain (lower scores mean less pain) Improved by 28% (ranging from 15% to 42% better) or by 28 points on a scale of zero to 100 points. People who had surgery rated their pain as 12.8 points. People who had sclerosing injection rated their pain as 41.1 points. Global assessment of success (participant-reported success, higher score is better) Improved by 34% (ranging from 19% to 49% better) or by 33.9 points on a scale of zero to 100 points. People who had surgery rated their pain as 86.8 points. People who had sclerosing injection rated their pain as 52.9 points. Withdrawals One person from each group (4%) withdrew from the study for reasons unrelated to the treatment. The study did not report on quality-of-life improvements, functional score improvements or adverse events (including tendon ruptures). We decided the evidence was low-certainty due to flaws in the design of the studies that may over-estimate benefits of treatment. For example, people involved in the study were aware of which treatment they were receiving, the studies selectively reported some results but not others, and there was imprecision in the results due to the small number of participants and trials. Therefore, we are uncertain if surgery has any benefits over eccentric exercises or sclerosing injections for treating patellar tendinopathy in adults. Further studies are likely to change the results.
Searches to 21 September 2015 identified 23 studies in which 3301 patients were treated with MPA (all studies used MMF) or AZA. Methodological quality of the studies was limited, e.g. only in two RCTs was the study medication administered in a blinded fashion. MMF was more effective than AZA for reducing the risk of graft loss (by approximately 20%) and acute rejection (by approximately 30%). No difference in mortality was observed. Moreover, graft function appeared to be similar in both treatments. When drugs are given to suppress the immune system, this can result in serious side effects such as infections and malignancies. The data on adverse events was limited by relatively short follow up in the studies as some of these side effects occur after several years of treatment. Furthermore, the studies did not focus on these harms and did not use harmonised diagnostic criteria. The incidence of cytomegalovirus infections did not differ between MMF and AZA, but there was a 1.7-fold increased risk for the more severe, tissue-invasive cytomegalovirus disease in MMF-treated patients. Information on malignancies was reported only in five studies; therefore no robust conclusions can be drawn. Gastrointestinal side effects (e.g. nausea, diarrhoea) were more common with MMF-treatment, whereas bone marrow suppression (e.g. thrombocytopenia) and elevated liver enzymes were observed more frequently in AZA treated patients. In general, evidence for efficacy outcomes is of high quality and can be seen as considerably robust, but there is less certainty on aspects of safety. Therefore, caregivers should balance potential benefits and harms of MMF and AZA according to individual patient's risks and preferences. Physicians need to individualise the decision between these agents as components of the immunosuppressive regimen.
We found two studies involving a total of 49 women. One was a six-week study comparing yoga to a waiting list (delayed treatment) in women with either stress or urgency urinary incontinence. The other was an eight-week study comparing yoga to mindfulness-based stress reduction (MBSR) in women with urgency urinary incontinence. We also identified an ongoing study involving 50 women that aims to compare yoga with stretching; we will include this study when the results are reported. The trial comparing yoga to a waiting list did not report the number of women reporting cure but did report on symptoms, condition-specific quality of life and adverse effects. While this comparison generally favoured the yoga intervention, we are uncertain whether yoga improves urinary incontinence due to the very low certainty of the evidence. There was no difference between groups in the number of women reporting an adverse event and no serious adverse events were reported, but we are uncertain whether yoga increases harms as the certainty of the evidence is very low. The trial comparing yoga to MBSR reported on symptoms and condition-specific quality of life but did not report the number of women reporting cure. While this comparison generally favoured the MBSR intervention, we are uncertain whether yoga improves urinary incontinence due to the very low certainty of the evidence. There was no information on adverse events. We did not find any information on the value for money of yoga for urinary incontinence. Although we identified some evidence on yoga treatment for treating urinary incontinence in women, the included studies were very small and there were issues with the way they were conducted, which limits our confidence in the results. Due to the nature of the treatments, the participants and staff of the trial comparing yoga to a waiting list were aware of which groups the participants were assigned and it is possible that the women in the yoga group reported some benefits because they expected yoga to be helpful. The trial comparing yoga to MBSR did not intend to test yoga as a treatment for incontinence. Instead, the trial tested MBSR as a treatment and used yoga classes to ensure that women in the comparison group received attention from the study staff. In addition, the trial comparing yoga to MBSR did not collect outcomes on all women and it is possible that the women who reported outcomes had either better or worse results than the women who did not report outcomes. There is currently insufficient good-quality evidence to judge whether yoga is useful for women with urinary incontinence.
We searched scientific databases for clinical trials comparing the antiepileptic medication, topiramate, with placebo (a pretend treatment) or another antiepileptic drug in people with JME. We wanted to evaluate how well topiramate worked and if it had any side effects. The evidence is current to July 2018. We included and analyzed three randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 83 participants. Based on the information in these trials, it seems that topiramate is better tolerated than valproate, but is no more effective than valproate. Topiramate seemed to work better than placebo, but this result was based on a small number of included people. The quality of the evidence from the studies was very low and the results should be interpreted with caution. More randomized controlled trials with large numbers of participants are required to test how effective and well tolerated topiramate is in people with JME. Future trials should be well-designed and double-blinded (where neither the participant nor the researcher know which treatment has been given until after the results have been collected). This review does not provide sufficient evidence to support topiramate for the treatment of people with JME.
We searched important medical databases for clinical trials assessing the benefits and harms of nivolumab in adults with HL. Two review authors independently screened, summarised and analysed the results. In addition, we tested the computer software RobotReviewer to extract data. Our search led to the inclusion of three studies involving 283 participants and 14 ongoing trials. The evidence provided is current to May 2018. Two studies with 260 participants evaluated survival. After six months, all participants were alive in one trial (17 participants). One trial reported quality of life for a subgroup of participants using a questionnaire but not all follow-up data were available. Although it seemed that the participants answering the questionnaire might have had a benefit, it was unclear whether this applied to all the participants. The studies also reported tumour control and tumour response, but with different results, depending on the treatment and how many previous treatments participants had received before nivolumab was given. As nivolumab is given until the disease progresses (gets worse) or until unacceptable side effects occur, people receive the drug for a long time. Therefore, reporting of side effects is related to the time the person received the medicine, with potentially more side effects with longer usage. The most commonly reported side effects were fatigue (tiredness), diarrhoea (loose stools), infusion reactions (during or shortly after giving the medicine by a vein) and rash. Only one study reported medicine-related serious side effects. They occurred rarely (infusion reactions and lung disease). Deaths related to the medicine were not reported. Due to the study design and varied type of participants with different numbers of previous treatments and various treatment options, the reliability of the evidence was low to very low. This systematic review evaluated the benefits and harms of nivolumab in adults with HL. Data on survival, quality of life, tumour response and side effects were available from small trials only. The three trials included only people different previous treatment options, very often also with a previous stem cell transplantation. In one trial, all participants were alive after six months. Quality of life data were not reported for all the included participants; moreover, data after a long period of treatment were not available for all evaluated participants, therefore meaningful conclusions were not possible. Serious side effects occurred rarely. Currently, data are too sparse to make a clear statement on nivolumab for people with relapsed or refractory HL except for those who had received several treatments before. As there are currently 14 ongoing trials evaluating nivolumab, of which two are well designed, it is possible that an update of this review will be published in the near future and that this update will show different results to those reported here.
This systematic review evaluates the effects of various herbal preparations (including single herbs or mixtures of different herbs) for treating people with type 2 diabetes. The review shows that some herbal medicines lower blood sugar and relieving symptoms in patients with diabetes. However, the methodological quality of the clinical trials evaluating these herbs is generally poor. The analyses also indicate that trials with positive findings are more likely to be associated with exaggerated effects. However, the trials did not report significant adverse effects. In conclusion, herbal medicines should not be recommended for routine use in diabetic patients of type 2 diabetes until we get scientifically sound trials. Testing the herbs in larger, well-designed trials is needed in order to establish the necessary evidence for their use.
We included 27 studies, with 1596 adults and children from 12 countries. Of these, 19 studies compared EPO with a placebo (dummy) treatment, and 8 used BO compared with placebo. We looked for evidence of overall improvement in eczema and in quality of life. All 27 studies evaluated overall improvement of eczema, but only 2 studies of EPO measured improvement in quality of life. There was no statistically significant advantage demonstrated for either EPO or BO compared to placebo. In summary, we did not find evidence that eczema improved by taking these products any more than it did by taking placebo. There was some evidence of mild and temporary side-effects for participants with either product or placebo, which were mainly mild, and included temporary headache and upset stomach or diarrhoea. With EPO there is an anticoagulant (blood-thinning) effect when taking these products. There is a warning with the blood thinner warfarin (Coumadin®) that taking EPO can increase bleeding. One report warns that if EPO is taken for a prolonged period of time (more than one year), there is a potential risk of inflammation, thrombosis, and immunosuppression due to slow accumulation of EPO in the tissues. Another reports a single case in which EPO was thought to have produced harms. We found no clinical evidence of such harm in these short-term trials. This systematic review found no evidence that either BO or EPO are effective in treatment of eczema. Both of these products and the placebos used in the studies had similar mild, temporary side-effects, which were mainly gastrointestinal.
This review aimed to determine the effectiveness and toxicity of gemcitabine by looking at the evidence published from randomised clinical trials. Patients receiving gemcitabine combined with cisplatin had a similar overall survival but less toxicity when compared to the well-established chemotherapeutic treatment of MVAC (methotrexate, vinblastine, doxorubicin, cisplatin). This suggests that gemcitabine plus cisplatin may be considered an alternative chemotherapy schedule to MVAC for advanced bladder cancer but the evidence is limited to one trial only. For patients who have poor kidney function or poor performance status the combination of gemcitabine plus carboplatin may be considered.
Both psychological therapy and pharmacotherapy have been used to treat PTSD and guidelines suggest that a combination of both may mean people recover from PTSD more effectively. Four trials including 124 participants were included in this review. One of these trials (n =24) was on children and adolescents. The trials all used SSRIs and prolonged exposure or a cognitive behavioural intervention. Only two trials reported on total PTSD symptoms but the data could not be combined. In this review, there are too few studies to be able to draw conclusions about whether a combination of psychological therapy and pharmacotherapy result in better outcomes for patients than either of these treatments alone.
The current review includes 39 trials with a total of 3509 participants and confirms its efficacy compared to placebo or no treatment. This finding is important, because the efficacy of antidepressants has recently been questioned. However, the review also demonstrated that amitriptyline produces a number of side effects such as vision problems, constipation and sedation. It is a limitation of this review that many studies have been poorly reported, which might have led to bias.
This review of the published literature found that patients who had their wounds closed with stitches healed faster and returned to work earlier than patients whose wounds were left unstitched and allowed to heal "naturally". However, the review also found that patients who had their wounds closed with stitches were more likely to get the disease again compared to those who did not have their wounds closed by stitches. This means that each type of surgical treatment has its advantages and disadvantages, and that the decision about which type of surgical wound to select should also be guided by the patient's own desired goals for treatment. The review also found that if a decision had been made to close the wound with stitches, then the best way to reduce the risk of the disease coming back and reduce other complications (such as infection), was to use a wound technique where the line of stitches was moved away from between the buttocks. Therefore one definitive recommendation from this systematic review is that where a decision has been made to close the sinus wound using stitches, this wound should not lie in the central area of the buttocks.
The review authors found one randomised controlled trial with 92 participants that considered fludarabine was superior to the alkylating agents-containing regimen for pretreated/relapsed patients with Waldenstrom's macroglobulinaemia.
We searched for trials that compared usual care with intensive insulin treatment (trying to keep blood sugar levels within the normal range of 4 to 7.5 mmol/L) after stroke. We found 11 trials involving 1583 participants. Trying to keep the blood sugar level within a tight range immediately after a stroke did not improve the outcomes of neurological deficit and dependency. It did, however, significantly increase the chance of experiencing very low blood sugar levels (hypoglycaemia), which can be harmful and can cause brain damage and death. On balance, the trials did not show any benefit from intensive control of blood sugar levels after stroke.
We looked at 52 randomised controlled trials (studies where people were allocated at random to one of two or more treatment or control groups) in this review. On average, the interventions lasted about 16 weeks, while investigators followed up participants for 6 to 12 months. The studies examined different kinds of psychosocial interventions: cognitive behavioural therapy (19 studies), contingency management (25 studies), motivational interviewing (5 studies), interpersonal therapy (3 studies), psychodynamic therapy (1 study) and 12-step facilitation (4 studies). Forty-one studies took place in the United States, four in Spain, three in Australia, two in Switzerland and two in the UK. We included a total of 6923 participants with an average age of 36 years. The proportion of males is 63%. The comparisons made were: any psychosocial versus no intervention (32 studies), any psychosocial versus treatment as usual (6 studies), and one psychosocial intervention versus an alternative psychosocial intervention (13 studies). Five of the included studies did not provide any useful data for inclusion in statistical synthesis. We found that, compared to no intervention, any psychosocial intervention probably improves treatment adherence and may increase abstinence at the end of treatment; however, people may not be able to stay clean several months after the end of treatment. Finally, we found that people undergoing specific psychosocial interventions stay clean for a longer time without using stimulants. However, the vast majority of the studies we looked at assessed a specific psychosocial treatment added to treatment as usual or compared it to another specific psychosocial or pharmacological treatment. So, control groups were not really untreated. This could have led to an underestimation of the true effect of the psychosocial interventions. We found that, when compared to TAU, any psychosocial treatment probably improves adherence but may not improve abstinence at the end of treatment nor help participants to stay clean for a longer time. We could not draw any conclusions on which is the most effective psychosocial treatment based on direct comparisons. Most of the studies took place in the United States, and this could limit the generalisability of the findings, because the effects of psychosocial treatments could be strongly influenced by the social context and ethnicity. None of the studies reported harms related to psychosocial interventions. The quality of evidence was moderate for adherence to treatment but low for abstinence.
We identified seven randomised controlled trials (studies in which the participants were divided between treatment groups through random method) (most recent search August 2018). Six studies compared balneotherapy versus no treatment, and one study compared balneotherapy versus a medicine called melilotus officinalis. The studies used different types of balneotherapy and different treatment times. For the balneotherapy versus no treatment comparison there probably is no improvement in favour of balneotherapy in disease severity signs and symptoms score (moderate-certainty evidence). Balneotherapy probably improves health-related quality of life and pain (moderate-certainty evidence). There probably is no improvement in favour of balneotherapy for leg ulcers (moderate-certainty evidence). There is no clear effect related to oedema (swelling caused when fluid leaks out of the body's tiny blood vessels) between balneotherapy and no treatment (very low-certainty evidence). Balneotherapy probably reduces skin pigmentation changes (low-certainty evidence). None of the studies reported any serious adverse events. There were fewer side effects (infection and blood clots in the legs) in people receiving balneotherapy compared to no treatment. When comparing balneotherapy with melilotus officinalis, there were insufficient data to detect clear differences between the two treatments for pain and oedema in the single small study. There were no data available for the other outcomes of interest such as disease severity signs and symptoms score, quality of life, leg ulcers and skin pigmentation. The certainty of the evidence was affected by the small number of trials with few participants and the impossibility of blinding of participants and physicians conducting the balneotherapy treatment, which could have led to bias.
This review identified 17 randomized studies that addressed whether more aggressive attempts to lower blood glucose levels prevent people from developing neuropathy. Seven of these studies were conducted in people with type 1 diabetes, eight in type 2 diabetes, and two in both types. However, only two studies in type 1 diabetes including 1228 participants and four studies in type 2 diabetes including 6669 participants investigated our primary outcome. In type 1 diabetes, there was a significant effect of more aggressive therapies in preventing neuropathy compared with standard treatment. In type 2 diabetes, more aggressive therapy was also beneficial in preventing symptoms and signs of clinical neuropathy, but the result was not statistically significant as measured by the primary method selected for this review. However, there was a significant positive effect on the amount of nerve damage measured with electrical nerve conduction tests and a special machine to measure the threshold of detection of vibration in both types of diabetes. Overall, the evidence indicates that more aggressive treatments of sugar levels delay the onset of neuropathy in both types of diabetes. No other treatments have proven effective to date. However, the beneficial effect has to be balanced against the significantly increased risk of dangerously low blood sugar levels that can occur in both types of diabetes and which can lead to brain injury amongst other issues.
The evidence is current to 17 April 2018. Of the 3840 records screened, we identified only one unpublished study that met our inclusion criteria. The intervention focused on women living in Ukraine with HIV undergoing medical abortion at home. The quality of evidence was low, but found that medical abortion was successful with no major complications experienced among women living with HIV. The results from this review do not provide enough evidence to determine if differences exist in abortion outcomes for women living with HIV, but also no evidence was found showing that abortion is unsafe in this population. As it is important for all women to have access to safe abortion to combat the public health threat of high rates of maternal deaths, healthcare providers should not be deterred from providing access to safe abortion to their patients living with HIV.
We found a total of 16 studies. They included mostly men, older than 60 years of age, with moderate, to severe urinary symptoms. Most studies were funded by the companies that make these drugs. Compared to placebo, phosphodiesterase inhibitors may make urinary symptoms a little better and reduce bother, but may also cause more unwanted drug effects. There is probably no difference between phosphodiesterase inhibitors and alpha-blockers when it comes to improving urinary symptoms, and there may be no difference with regards to how bothersome symptoms are, or unwanted drug effects. Taking a phosphodiesterase inhibitor with an alpha-blocker may improve urinary symptoms slightly more than taking alpha-blockers alone. We found no evidence regarding urinary bother. However, combination treatment probably causes a lot more unwanted drug effects. Taking a phosphodiesterase inhibitor with an alpha-blocker may improve urinary symptoms slightly more than taking a phosphodiesterase inhibitor alone. We found no evidence regarding bother or unwanted drug effects. In the short term (up to 12 weeks), the combination of a phosphodiesterase inhibitor with a 5-alpha reductase inhibitor probably makes urinary symptoms a little better compared to taking a 5-alpha reductase inhibitor alone, but the effect may be too small to notice. We found no evidence on bother, nor on rates of unwanted drug effects. When taken longer (13 to 26 weeks), combination treatment probably also improves urinary symptoms slightly to a degree that may not be noticeable. We found no evidence regarding urinary bother. Unwanted drug effects may be similar. We found no evidence for other combination treatments or comparing different phosphodiesterase inhibitors. Most studies investigated only short-term use of these drugs (up to 12 weeks); therefore, long-term effects are largely unknown. We mostly rated the quality of evidence as moderate or low, meaning that we are somewhat or quite unsure of the true results. The real effects may be similar or quite different.
This review examines the extent to which parenting programmes (relatively brief and structured interventions that are aimed at changing parenting practices) are effective in treating physically abusive or neglectful parenting. A total of seven studies of mixed quality were included in the review. The findings show that there is insufficient evidence to support the use of parenting programmes to reduce physical abuse or neglect (i.e. using objective assessments of abuse such as reports of child abuse; children on the children protection register etc). There is, however, limited evidence to show that some parenting programmes may be effective in improving some outcomes that are associated with physically abusive parenting. There is an urgent need for further rigorous evaluation of the effectiveness of parenting programmes that are specifically designed to treat physical abuse and neglect, either independently or as part of broader packages of care.
We included all studies (randomised controlled trials) comparing one type of medicine against another, or against an inactive medicine (placebo). We carefully looked at study results and tried to assess those that would be important to doctors, nurses and parents. We found a lot of differences between studies, and the small numbers of children included in the studies, the short follow-up provided and differing outcomes made combining the data (meta-analysis) in a meaningful way difficult. Overall as a result of the small numbers of children recruited to these studies, we could not be certain whether medicines improve symptoms. We found little evidence to suggest that medicines for babies younger than one year work, especially for functional reflux; mixed evidence has been found on whether Gaviscon Infant®  helps, and for infants with reflux disease (changes on pH studies or on endoscopy), medicines like omeprazole and lansoprazole are likely to help. In older children, proton pump inhibitors and histamine antagonists work better to improve symptoms, endoscopy appearances and pH probe findings, but we were unable to perform a meta-analysis, or to assess further whether one medicine was superior to another. Overall available evidence was of moderate to low quality, depending on the medicine in question. We have made suggestions as to how future studies could be designed to provide better answers regarding which treatments are best for babies and children with reflux or reflux disease.
We identified three randomised controlled trials that compared tacrolimus with cyclosporin in patients who had received lung transplants. We found no difference in survival or rejection of the donated lungs with the drugs in lung transplant recipients. Tacrolimus seemed better in preventing serious inflammatory lung and airways diseases (bronchiolitis obliterans syndrome and lymphocytic bronchitis), and high blood pressure. Diabetes may occur more often in patients treated with tacrolimus compared with cyclosporin-treated patients. More patients who received tacrolimus continued treatment compared with those treated with cyclosporin. However, these observations should be viewed cautiously because all three trials were flawed in design, the ways they were conducted, and in random errors. There were very few trials found that compared tacrolimus and cyclosporin after lung transplantation, and the numbers of patients and events were low. Better-designed and conducted studies are needed to inform clinical decisions for people who receive lung transplants.
We did a computer search for studies of birth control pills with two phases versus pills with one phase. We also wrote to researchers and manufacturers to find other trials. We included randomized trials in any language. We found only one trial that looked at one-phase versus two-phase birth control pills. The study authors did not report all their methods. Many of the women dropped out of the trial, and the authors did not give the reasons. The pills did not differ in any major ways, including bleeding patterns and the numbers of women who stopped using the pills. This review did not find enough evidence to say if two-phase pills worked any better than one-phase types for birth control, bleeding patterns, or staying on the pill. The one trial report had method problems and lacked data on pregnancies. Therefore, one-phase pills are the better choice, since we have much more evidence for such pills and two-phase pills have no clear reason for use.
For the original review, we found six studies with 1342 participants. For this update we searched up to December 2014, but found no additional studies. Ibuprofen 400 mg plus high doses of codeine (25.6 mg to 60 mg) provided effective pain relief for over 6 in 10 (64%) of participants, compared with just under 2 in 10 (18%) of participants with placebo (high quality evidence). Adverse events occurred at similar rates with the ibuprofen/codeine combination and placebo in these single dose studies (moderate quality evidence). No serious adverse events or withdrawals due to adverse events occurred with the combination. It is important not to exceed the recommended dose for this combination painkiller.
This review considered the efficacy, acceptability and adverse effects of olanzapine in long-term treatment of bipolar disorder in comparison with placebo or other active drug comparisons. Five trials (1165 participants) met the inclusion criteria and are included in the review. Based on a limited amount of information, olanzapine may prevent further mood episodes (especially manic relapse) in patients who responded to olanzapine during an index manic or mixed episode and who have not previously had a satisfactory response to lithium or valproate. The olanzapine group had significantly fewer patients suffering from insomnia than the placebo group, but a significantly larger number of people suffering from weight gain. When compared with lithium, olanzapine caused more weight gain and depressive symptoms but fewer insomnia and nausea symptoms and a lower rate of manic worsening. However, considering the lack of clear findings of this review, conclusions on efficacy and acceptability of olanzapine compared to placebo, lithium or valproate cannot be made with any degree of confidence
We identified two trials involving 154 minimally verbal children who had ASD (aged 32 months to 11 years). The studies randomly divided participants into those that received a communication intervention and a control group that did not receive the intervention but received treatment as usual in the community. Both studies focused primarily on communication outcomes (verbal and non-verbal). One of the studies also collected information on social communication. Neither study collected information on adverse events, other communication skills, quality of life or behavioural outcomes. One study looked at an alternative and augmentative communication (ACC) intervention (Picture Exchange Communication System; PECS), which teachers gave the children in school. This intervention was conducted over five months and involved teacher training and consultation. PECS is a staged approach where children are taught to exchange a single picture of a desired item or action to another person who then responds to the request. The system progresses toward putting pictures together in sentences and using these sentences in a variety of ways such as commenting and answering questions. This study included 84 participants (73 boys) aged 4 to 11 years and was funded by the Three Guineas Trust. The other study looked at a verbally based intervention (focused playtime intervention; FPI), which is a home-based parent education programme that aims to promote coordinated play with toys between parents and their children. This study included 70 participants (64 boys) aged 32 months to 82 months and was funded by a Clinical and Patient Educators Association grant (HD35470) from the National Institute of Child Health and Human Development, the MIND Institute Research Program, and a Professional Staff Congress-City University of New York grant. There is limited evidence that verbally based and AAC interventions improve spoken and non-verbal communication in minimally verbal children with ASD. Both studies included in this review reported gains in aspects of verbal or non-verbal communication (or both) for some children immediately after the intervention. Neither of the interventions resulted in improvements in verbal or non-verbal communication that were maintained over time for most children. We rated the overall quality of the evidence as very low because we only found two eligible studies, and they involved few participants. Furthermore, both studies had some methodological limitations that increased their risk of bias. There is currently limited evidence that verbally based and ACC interventions improve expressive communication skills in minimally verbal children with ASD aged 32 months to 11 years. Additional trials that use communication interventions and compare the effects of these interventions to a control group are urgently required to build the evidence base.
Trials have tried giving chemotherapy (drugs) after these standard treatments to find out whether it can help people to live longer. This review found that giving chemotherapy after either radiotherapy or supportive care did seem to help patients live longer. Giving chemotherapy after radiotherapy to 1000 patients would mean that an extra 40 patients would be expected to be alive 2 years later, than if the chemotherapy was not given. Giving chemotherapy after supportive care to 1000 patients would mean that 100 more would be expected to be alive 2 years later, than if the chemotherapy was not given. Chemotherapy after surgery may also help patients live longer although the evidence to support this is less clear.
This review aimed to evaluate the existing literature to see if rutosides were useful for treating PTS. We also investigated whether there were any side effects from the treatment. We searched all existing databases for trials relating to the use of rutosides for the treatment of PTS following DVT (current until 21 August 2018). Two review authors independently assessed the trials for inclusion and extracted results in line with our prescribed criteria. We found three suitable trials, with a total of 233 patients, and six unsuitable trials that were not included in the review. The studies were small and undertaken very differently meaning they could not be combined. The studies used different comparisons with rutosides (placebo (inactive product), compression stockings alone or combined with rutosides, or hidrosmina (a venoactive drug, which acts on the vascular system). They also used different doses of rutosides (900 mg/day to 2000 mg/day). We found no clear evidence from any of the trials that treatment with rutosides improved symptoms and signs of PTS; or that there was any difference in side effects. Occurrence of leg ulceration was not reported in any of the included studies. Overall quality of evidence, using the GRADE approach, was low mainly due to the lack of both participant and researcher blinding. This means both investigators and participants knew what drug they were getting and this can effect the results. The quality of the evidence was further limited as only three small studies contributed to the review findings. A subjective scoring system was used to obtain the symptoms of PTS so it was important that the assessors were blinded to the intervention.
Green tea has a long history of many uses, one of which is helping overweight people to lose weight and to maintain weight loss. Believed to be able to increase a person's energy output, green tea weight loss preparations are extracts of green tea that contain a higher concentration of ingredients (catechins and caffeine) than the typical green tea beverage prepared from a tea bag and boiling water. This review looked at 15 weight loss studies and three studies measuring weight maintenance where some form of a green tea preparation was given to one group and results compared to a group receiving a control. Neither group knew whether they were receiving the green tea preparation or the control. A total of 1945 participants completed the studies, ranging in length from 12 to 13 weeks. In summary, the loss in weight in adults who had taken a green tea preparation was statistically not significant, was very small and is not likely to be clinically important. Similar results were found in studies that used other ways to measure loss in weight (body mass index, waist circumference). Studies examining the effect of green tea preparations on weight maintenance did not show any benefit compared to the use of a control preparation. Most adverse effects, such as nausea, constipation, abdominal discomfort and increased blood pressure, were judged to be mild to moderate and to be unrelated to the green tea or control intervention. No deaths were reported, although adverse events required hospitalisation. One study attempted to look at health-related quality of life by asking participants about their attitudes towards eating. Nine studies tracked participants' compliance with green tea preparations. Studies did not include any information about the effects of green tea preparations on morbidity, costs or patient satisfaction.
We included two studies with a total of 40 people (35 from one study and five from a second study). Of these people, 21 participated in exercise training and 19 did not participate in exercise training. All people were men and they were between 55 and 86 years old. Both exercise training programmes included cycling and walking and one programme also included strength training exercises. In both studies, training lasted for eight weeks with people attending two to three sessions per week. Immediately following exercise training, people walked an average of 53.81 metres further in a six-minute walk test than those who did not complete exercise training. Six months following exercise training, people walked 52.68 metres further in a six-minute walk test than those who did not complete exercise training. These improvements in exercise capacity were similar for people with dust-related interstitial lung disease and people with asbestos related pleural disease. Quality of life also improved more in people who exercised compared to those who did not. No one reported experiencing any unwanted effects due to exercise training. The quality of evidence was very low because there were only two studies and 40 people. Therefore, it is likely that these findings will change with more studies in the future. We need bigger studies that can confirm the findings of this Cochrane review.
This review examined 19 studies with 1496 participants to see whether there is a difference in effectiveness between conventional and newer antibiotics. This review found no differences. Adverse effects in both approaches were similar, except for diarrhoea, which was more common in the cephalosporin group. Only three studies dealt with adults; the remaining studies recruited participants aged 15 years and younger. Therefore, we believe that the results probably pertain more to children. Conventional and newer antibiotics seem reasonable options for initial, immediate treatment. The choice may depend on availability, affordability and local policies.
Researchers from the Cochrane Collaboration examined the evidence available up to August 5, 2013. Fourteen studies tested six herbal medications and included 2050 adults with non-specific acute or chronic LBP. Two oral herbal medications,Harpagophytum procumbens(devil's claw) andSalix alba(white willow bark), were compared to placebo (fake or sham pills) or to rofecoxib (Vioxx®). Three topical creams, plasters, or gels,Capsicum frutescens(cayenne),Symphytum officinaleL. (comfrey), andSolidago chilensis(Brazilian arnica), were compared to placebo creams or plasters and a homeopathic gel. One essential oil, lavender, was compared to no treatment. The average age of people included in the trials was 52 years and studies usually lasted three weeks. Devil's claw, in a standardized daily dose of 50 mg or 100 mg harpagoside, may reduce pain more than placebo; a standardized daily dose of 60 mg reduced pain about the same as a daily dose of 12.5 mg of Vioxx®. While willow bark, in a standardized daily dose of 120 mg and 240 mg of salicin reduced pain more than placebo; a standardized daily dose of 240 mg reduced pain about the same as a daily dose of 12.5 mg of Vioxx® (a non-steroidal, anti-inflammatory drug). Cayenne was tested in several forms: in plaster form, it reduced pain more than placebo and about the same as the homeopathic gel Spiroflor SLR. Two other ointment-based medications,S. officinaleandS. chilensisappeared to reduce perception of pain more than placebo creams. Lavender essential oil applied by acupressure appeared effective in reducing pain and improving flexibility compared to conventional treatment. Adverse effects were reported, but appeared to be primarily confined to mild, transient gastrointestinal complaints or skin irritations. Most included trials were at low risk of bias and the quality of the evidence was mainly very low to moderate. A moderate grade of evidence was only found forC. frutescens. Trials only tested the effects of short term use (up to six weeks). Authors of eight of the included trials had a potential conflict of interest and four other authors did not disclose conflicts of interest. Vioxx® has been withdrawn from the market because of adverse effects, so all three substances should be compared to readily-available pain medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, for relative effectiveness and safety. Low to moderate quality evidence shows that four herbal medicines may reduce pain in acute and chronic LBP in the short-term and have few side effects. There is no evidence yet that any of these substances are safe or efficacious for long-term use. Large, well-designed trials are needed to further test the efficacy of these interventions.
This review was carried out in order to assess the effect of the various processes of peer review on the quality of funded research. Only ten studies were included and described in the review. We were unable to find comparative studies assessing the actual effect of peer review procedures on the quality of the funded researchThere is little empirical evidence on the effects of grant giving peer review. Experimental studies assessing the effects of grant giving peer-review on importance, relevance, usefulness, soundness of methods, soundness of ethics, completeness and accuracy of funded research are urgently needed. Practices aimed to control and evaluate the potentially negative effects of peer review should be implemented meanwhile.
We included seven studies (1202 participants), in which the participants were allocated at random (by chance alone) to receive one of several clinical interventions, where Daikenchuto was compared with any other medicine, placebo, or no treatment. The searches were performed 3 July 2017. We evaluated: time from completion of abdominal surgery to first flatus, time to first bowel movement, time to resumption of regular solid food intake, adverse events related to Daikenchuto, patient satisfaction, re-interventions for postoperative ileus before leaving hospital, and length of hospital stay. Overall, there were a small number of participants included in each analysis. We could not fully investigate time from surgery to first flatus, to first bowel movement, or to resumption of regular solid food intake, any medicine-related adverse events, patient satisfaction, any re-interventions for postoperative ileus before leaving hospital, or length of hospital stay. We considered the quality of evidence for all presented outcomes as moderate to very low. Based upon our findings, it was uncertain whether Daikenchuto accelerated post-surgical bowel motility in persons undergoing abdominal surgery, and thus, unclear whether Daikenchuto reduced postoperative ileus.
We searched scientific databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) that compared Morita therapy with treatments with medicines or other psychological therapies (e.g. talking therapies), no treatment or wait list control (where people are waiting to receive a treatment) of adults with anxiety disorders. The evidence was current to December 2014. We found seven small Chinese studies with 449 participants to include in the review. Six of the seven studies provided useable data for us to analyse; they assessed Morita therapy for generalised anxiety disorder (a long-term illness that causes people to feel anxious about a wide range of situations and issues; one study), social phobia (a persistent fear about social situations and being around people; two studies) and obsessive-compulsive disorder (where a person has obsessive thoughts and repetitive behaviours; three studies). However, these studies were small, imprecise and contained considerable risks of bias, so we were unable to draw conclusions on the effectiveness of Morita therapy in the treatment of anxiety disorders. The review highlighted the need for high-quality studies to assess the efficacy of Morita therapy on anxiety disorders.
Our review included 17 small trials, involving a total of 366 participants. Study quality was low. Fourteen trials compared cold-water immersion applied after exercise with 'passive' treatment involving rest or no treatment. The temperature, duration and frequency of cold-water immersion varied between the different trials as did the exercises and settings. There was some evidence that cold-water immersion reduces muscle soreness at 24, 48, 72 and even at 96 hours after exercise compared with 'passive' treatment. Limited evidence from four trials indicated that participants considered that cold-water immersion improved recovery/reduced fatigue immediately afterwards. Most of the trials did not consider complications relating to cold-water immersion and so we cannot say whether these are a problem. There were only limited data available for other comparisons of cold-water immersion versus warm or contrasting (alternative warm/cold) water immersion, light jogging, and compression stockings. None of these showed important differences between the interventions being compared. While the evidence shows that cold-water immersion reduces delayed onset muscle soreness after exercise, the optimum method of cold-water immersion and its safety are not clear.
This review of three trials failed to identify a difference between azithromycin and benzathine penicillin G for early syphilis in the odds of cure rate, with the result being too imprecise to confidently rule out the superiority of either treatment option. Although gastrointestinal adverse effects were more common in the participants on azithromycin, than in those given benzathine penicillin G, the difference with benzathine penicillin did not reach statistical significance. More research is required in this area.
Trials of opiates compared to sedatives or other non-pharmacological treatments have generally been of poor quality. Individual trials have reported that using an opiate compared to phenobarbitone may reduce the incidence of seizures, duration of treatment and nursery admission rate. However, no overall effect was found on treatment failure rate. When compared to diazepam, opiates reduced the incidence of treatment failure. Opiates such as morphine or dilute tincture of opium should probably be used as initial treatment for opiate withdrawal in newborn infants.
Eleven randomised controlled trials were included in the review, none of which were of high quality. A large number of trials were excluded, mainly because of their non-randomised designs. There appeared to be a short-term effect of approximately 50% hair reduction with alexandrite and diode lasers up to six months after treatment, whereas there was little evidence for an effect with intense pulsed light, neodymium:YAG or ruby lasers. Long-term hair removal was not recorded for any treatment. Infrequently reported adverse effects were pain, skin redness, swelling, burned hairs and pigmentary changes.
We examined the research published up to 12 September 2012 and we identified 10 studies for inclusion in this systematic review. In eight studies all people with fever were treated with antimalarial drugs by community health workers and in two studies community health workers were trained to confirm malaria in people using RDTs. Home- or community-based strategies probably increase the number of people with fever that receive an effective antimalarial within 24 hours (moderate quality evidence). They probably reduce the number of deaths in areas where malaria is common and there is poor access to health services (moderate quality evidence) but to date this has only been demonstrated in one study from a rural setting in Ethiopia. We do not know whether they reduce the number of people requiring admission to hospital (very low quality evidence), or the number of people with evidence of malaria infection in their blood (very low quality evidence). Home- or community-based programmes may have little or no effect on the number of people with anaemia (low quality evidence). None of the included studies reported on adverse effects of using home- or community-based programmes for treating malaria. Use of RDTs instead of clinical diagnosis in home- or community-based programmes for treating malaria probably reduces the overuse of antimalarials drugs (moderate quality evidence) and may have little or no difference upon the number of childhood deaths (low quality evidence), the number of children with evidence of malaria infection in their blood (low quality evidence), or the need for children to be admitted to hospital (low quality evidence) compared to use of clinical diagnosis.
Seventeen randomised controlled trials involving over 3,300 people were included in the review. One study comparing sclerotherapy to compression stockings in pregnancy found that sclerotherapy improved symptoms and cosmetic appearance. There was no overall benefit from using alternative agents to STD (four trials), or any evidence that a foam is superior to liquid (two trials). Adding local anaesthetic to the sclerosing agent did reduce the pain of injection in one study. Neither the type, nor duration of elastic compression (seven studies) or type of pressure pad (one study) after sclerotherapy had any clear effect on the effectiveness of sclerotherapy, on varicose vein recurrence rates, cosmetic appearance or symptomatic improvement, or on complications. Many of the included studies took place in the 1980s and there is very limited evidence on which to assess the merits of sclerotherapy for treatment of varicose veins or comparing graduated compression stockings to sclerotherapy. There were no controlled trials comparing sclerotherapy for thread veins with either laser treatment or simple observation; hypertonic dextrose had similar efficacy in terms of sclerosis to STD in one study.
We searched the medical literature up to March 2016 for all randomised trials that compared any medicine used for treating sleep problems in people with dementia with a fake medicine (placebo). We found six trials (326 participants) that investigated three medicines: melatonin (four trials), trazodone (one trial), and ramelteon (one trial). The ramelteon trial and one melatonin trial were commercially funded; the other trials had non-commercial funding sources. Limited information was available for the ramelteon trial, and it came from the trial's sponsor. Overall, the evidence was of low quality, meaning that further research is very likely to affect the results. Participants in the melatonin and trazodone trials almost all had moderate to severe dementia, while those in the ramelteon trial had mild to moderate dementia. The four melatonin trials had a total of 222 participants. From the evidence we found, we could be moderately confident that melatonin did not improve sleep in patients with dementia due to Alzheimer's disease. No serious harms were reported. The trazodone trial had 30 participants. Because it was so small, we could only have limited confidence in its results. It showed that a low dose of the sedative anti-depressant trazodone, 50 mg, given at night for two weeks, increased the total time spent asleep each night by an average of 43 minutes. This medicine improved sleep efficiency (the percentage of time in bed spent sleeping), but had no effect on the time spent awake after falling asleep, or on the number of times the participants woke up at night. No serious harms were reported. The ramelteon trial had 74 participants. The limited information available did not provide any evidence that ramelteon was better than placebo. There were no serious harms caused by ramelteon. The trials did not report on some of the outcomes which interested us, including quality of life and the impact on carers. Although we searched for them, we were unable to find any trials of other sleeping medications that are commonly prescribed to people with dementia. All of the participants had dementia due to Alzheimer's disease, although sleep problems are also common in other forms of dementia. We concluded that there is very little evidence to guide decisions about medicines for sleeping problems in dementia. Any medicine used should be used cautiously, with a careful assessment of how well it works, and its side effects in individual patients. More trials are needed to inform medical practice, with a particular need for trials investigating medicines that are commonly used for sleep problems in dementia. It is essential that trials include careful assessment of side effects.
In this updated review, we identified 26 randomised controlled trials (represented by 6070 participants) that assessed the effects of SMT in patients with chronic low-back pain. Treatment was delivered by a variety of practitioners, including chiropractors, manual therapists and osteopaths. Only nine trials were considered to have a low risk of bias. In other words, results in which we could put some confidence. The results of this review demonstrate that SMT appears to be as effective as other common therapies prescribed for chronic low-back pain, such as, exercise therapy, standard medical care or physiotherapy. However, it is less clear how it compares to inert interventions or sham (placebo) treatment because there are only a few studies, typically with a high risk of bias, which investigated these factors. Approximately two-thirds of the studies had a high risk of bias, which means we cannot be completely confident with their results. Furthermore, no serious complications were observed with SMT. In summary, SMT appears to be no better or worse than other existing therapies for patients with chronic low-back pain.
A total of 262 infants born preterm have been enrolled in two studies of early versus late administration of EPO to prevent blood transfusions. There were no demonstrable benefits of early versus late administration of EPO with regards to reduction in the use of red blood cell transfusions, number of transfusions, the amount of red cells transfused or number of donor exposures per infant. However, the use of early EPO compared with late EPO administration increases the risk of retinopathy of prematurity, a serious complication in babies born before term. Currently, there is a lack of evidence that either treatment confers any substantial benefits with regard to any donor blood exposure, as many infants enrolled in both studies were exposed to donor blood prior to study entry, and early EPO increases the risk of retinopathy of prematurity. Neither early nor late administration of EPO is recommended.
We reviewed original research papers for evidence on the accuracy of physical tests for shoulder impingement or associated damage, in people whose symptoms and/or history suggest any of these disorders. To find the research papers, we searched the main electronic databases of medical and allied literature up to 2010. Two review authors screened assessed the quality of each research paper and extracted important information. If multiple research papers reported using the same test for the same condition, we intended to combine their results to gain a more precise estimate of the test's accuracy. We included 33 research papers. These related to studies of 4002 shoulders in 3852 patients. None of the studies exclusively looked at patients from primary care, though two recruited some of their patients from primary care. The majority of studies used arthroscopic surgery as the reference standard. There were 170 different target condition/index test combinations but only six instances where the same test was used in the same way, and for the same reason, in two studies. For this reason combining results was not appropriate. We concluded that there is insufficient evidence upon which to base selection of physical tests for shoulder impingement, and potentially related conditions, in primary care.
In this review, we systematically searched published and unpublished accounts of interventions that had been rigorously tested . We found three eligible independently conducted randomised controlled trials testing three different interventions. All three were conducted in the United States, amongst a total of 615 homeless, male and female youth. Due to the varied delivery of interventions, outcome measurement and reporting, we were unable to aggregate outcomes to estimate summary of effect measures. The significant risk of bias associated with the three included studies and their heterogeneity necessitate caution in interpreting the effectiveness of interventions to modify sexual risk behaviour for preventing HIV in homeless youth. While studies among homeless youth are highly challenging, future trials should comply with rigorous methodology in design, delivery, outcome measurement and reporting as well as consider the changing facets of homeless youth when designing HIV prevention tools.
We reviewed the literature to determine the benefits and harms of antihypertensive treatment in people with diabetes who did not have signs of kidney disease. We found 26 studies involving 61,264 participants that compared antihypertensive drugs with placebo (an neutral agent with no therapeutic benefits or harms), no treatment, and other antihypertensive drugs. A family of drugs called ACEi (angiotensin-converting enzyme inhibitors) has been shown to prevent new onset of kidney disease and reduce the numbers of deaths in people with diabetes who have normal levels of albumin in their urine compared with placebo or calcium channel blocking drugs. We found no significant effect from angiotensin receptor blocker (ARB) drugs on either development of ESKD or death. Subgroup analyses that suggested similar benefits from ARB for people with type 2 diabetes who were at high risk of heart disease or should be interpreted cautiously. Direct comparison of ACEi and ARB in this population showed no difference in preventing DKD. The benefits of ACEi are consistent, and ACEi could be the first choice intervention for primary prevention of DKD.
This review of 10 studies evaluated six different drugs. The only drug for which there was any evidence of benefit was piracetam, but the evidence of benefit was weak and there were concerns about its safety. It was not possible to conclude whether piracetam was more effective than speech and language therapy in treating aphasia after stroke. More research is needed into the effects of piracetam on aphasia, and its safety, before it can be recommended for routine use.
This update of the review of available clinical trials found that the risk of developing active TB was reduced when people infected with both HIV and TB used isoniazid. Isoniazid for latent TB is usually taken for six to 12 months, but more research is still needed to show optimal duration of treatment, the best treatment regime for people with HIV, and especially the best regimen in combination with HIV drugs.
We searched databases for studies which were randomised controlled trials (RCTs) of computer/Internet-based interventions which aimed to improve sexual health. We included trials of computer-based interventions delivered to people of any age, gender, sexual orientation, ethnicity or nationality. The review evaluated 15 RCTs involving 3917 participants. Results showed that computer-based interventions have a moderate effect in improving people's knowledge about sexual health in comparison to minimal interventions such as ‘usual practice' or a leaflet. We also found a small effect on safer sex self-efficacy (a person's belief in their capacity to carry out a specific action), a small effect on safer-sex intentions, and also an effect on sexual behaviour (such as condom use for sexual intercourse). We found that computer-based interventions seem better than face-to-face interventions at improving sexual health knowledge, but there were insufficient data to analyse other outcomes. No studies measured potential harms (apart from reporting any deterioration in outcomes). Interactive computer-based interventions for sexual health promotion are feasible in a variety of settings. They are effective tools for learning about sexual health, and they also improve self-efficacy, intention and sexual behaviour, but more research is needed to establish whether computer-based interventions can change outcomes such as sexually transmitted infections and pregnancy, to understand how interventions might work, and to assess whether they are cost-effective.
We found 19 randomised controlled trials that looked at the effect of antibiotic prophylaxis on post-abortal upper genital tract infection amongst women requesting induced abortion in the first trimester of pregnancy. We looked at the effect of any antibiotic prophylaxis regimen on the outcome. Overall, the risk of post-abortal upper genital tract infection in women receiving antibiotics was 59% that of women who received placebo. There were, however, differences between the trial results over and above what would be expected by chance alone. It should be noted that, if the infection is caused by a sexually transmitted organism, antibiotic prophylaxis will not protect the woman from becoming re-infected if her sexual partner has not been treated. None of the trials was done in lower or middle income countries, which is where the risk of post-abortal complications is highest. Further trials are needed to determine whether combinations of antibiotics can prevent more infections than single antibiotics, or whether antibiotic prophylaxis should be restricted to women with positive results of screening tests before the abortion.
This review examined the effects of the high-potency antipsychotic fluphenazine compared with those of low-potency antipsychotics. A search for randomised trials comparing these types of drugs was carried out in 2010. The review includes seven studies with 1567 participants. Pooled data from two of these trials did not show a clear difference in effectiveness between fluphenazine and low-potency antipsychotics. However, evidence showed fluphenazine produced more movement disorders than low-potency antipsychotics, whereas the low-potency drugs were more likely to cause dizziness, drowsiness and sedation, a dry mouth, nausea and sometimes even vomiting. The number of included studies was low and the quality of evidence provided was moderate. Therefore, further good quality studies would be needed to draw firm conclusions about the relative effectiveness of fluphenazine compared to low-potency antipsychotics. Important information on service use, going into hospital again (rehospitalisation), costs and quality of life was missing and not reported. This plain language summary was written by a consumer Ben Gray from RETHINK mental illness.
The researchers extensively searched the literature up to 17 October 2018 and found three studies (93 participants) that met the inclusion criteria. One ongoing study was also identified. All of the studies were small in size and had some quality issues. One small study (21 participants) compared eight weeks of treatment with cannabis cigarettes containing 115 mg of D9-tetrahydrocannabinol (THC) to placebo cigarettes containing cannabis with the THC removed in participants with active Crohn's disease who had failed at least one medical treatment. Although no difference in clinical remission rates was observed, more participants in the cannabis group had improvement in their Crohn's disease symptoms than participants in the placebo group. More side effects were observed in the cannabis cigarette group compared to placebo. These side effects were considered to be mild in nature and included sleepiness, nausea, difficulty with concentration, memory loss, confusion and dizziness. Participants in the cannabis cigarette group reported improvements in pain, appetite and satisfaction with treatment. One small study (22 participants) compared cannabis oil (10 mg of cannabidiol twice daily) to placebo oil (i.e. olive oil) in participants with active Crohn's disease who had failed at least one medical treatment. No difference in clinical remission rates was observed. There was no difference in serious side effects. Serious side effects included worsening Crohn's disease in one participant in each group. One small study (50 participants) compared cannabis oil (composed of 15% cannabidiol and 4% THC) to placebo oil in participants with active Crohn's disease. Positive differences in quality of life and the Crohn's disease activity index were observed. The effects of cannabis and cannabis oil on Crohn's disease are uncertain. No firm conclusions regarding the benefits and harms (e.g. side effects) of cannabis and cannabis oil in adults with Crohn's disease can be drawn. The effects of cannabis and cannabis oil in people with Crohn's disease in remission have not been investigated. Further studies with larger numbers of participants are required to assess the potential benefits and harms of cannabis in Crohn's disease. Future studies should assess the effects of cannabis in people with active and inactive Crohn's disease. Different doses of cannabis and formulations (e.g. cannabis oil or pills) should be investigated.
Two trials to date have assessed use of dextrose gel to reverse low blood glucose levels while the baby remains in the mother's care; these studies included a total of 312 infants. Investigators rubbed dextrose gel into the inside of the infant's cheek; they provided a normal feed for 157 of these infants and placebo gel plus a normal feed, or a normal feed alone, for 155 infants.Key results:Results suggest that dextrose gel is effective in keeping mothers and infants together and improving the rate of full breast feeding after discharge from hospital. Researchers reported no adverse effects when dextrose gel was given to infants and no effects on development at two years of age. The review is limited by lack of data for the important outcomes of effectiveness of treatment for individual episodes of low blood glucose levels and effects on brain injury. Further research is required to address these important questions. Dextrose gel applied to the inside of the cheek is a simple and safe treatment for initial care of infants with low blood glucose levels. Overall the quality of the evidence was moderate to very low. Reasons for downgrading the quality of evidence included imprecision (variation in data), publication bias (evidence based on data from a single trial; one publication in abstract format only), insufficient detail to allow a judgement about risk of bias and/or high levels of disagreement for a particular outcome.
In this review we aimed to determine whether there is evidence for the effectiveness of inhaled sodium cromoglycate as maintenance treatment in children with chronic asthma. Most of the studies were carried out in small groups of patients. Furthermore, we suspect that not all studies undertaken have been published. The results show that there is insufficient evidence to be sure about the beneficial effect of sodium cromoglycate compared to placebo. However, for several outcome measures the results favoured sodium cromoglycate.
We included three randomised controlled trials involving a total of 230 women. These studies compared lidocaine poured into the abdominal cavity with a placebo, or other treatments, such as an injection of morphine (also known as an opioid) into the muscle, or combination of lidocaine and morphine. All studies took place in Thailand. The evidence described here are from studies published before 31 July, 2017. Pouring lidocaine into the abdominal cavity during a mini-laparotomy tubal ligation before fallopian tubes were tied after delivery may offer better pain control than a placebo or morphine injection, although the evidence regarding adverse effects is uncertain. Women who received a combination of morphine injection and lidocaine poured into the abdominal cavity showed no clear difference in pain with those who received lidocaine alone. An injection of morphine into the muscle alone did not reduce pain more than a placebo. The certainty of evidence regarding the effectiveness of these interventions was low due to risk of bias and imprecision of results. The certainty of evidence regarding the safety of the interventions was very low because of risk of bias and imprecision.
This review found only two eligible clinical trials which had been carried out in the last 10 years and both were of bodyworn absorbent products. These trials included all the product designs and took place in nursing homes and in the community (i.e. involving people living in their own homes); both were carried out in the UK. There is evidence that different designs are better for men and women. Of the disposable designs diapers are the most cost-effective for men for both day and night. Women prefer disposable pull-ups, but they are expensive and disposable inserts are a cost-effective alternative (except for women at night in nursing homes where disposable diapers are better). Washable diapers are inexpensive but have limited acceptability, confined mainly to some men at night. There were not enough people in the trials to draw any conclusions about which designs are best for faecal incontinence or about which particular design was better or worse for skin health. Using combinations of designs (different designs for day/night or for staying in/going out) may be more effective and less expensive than using one design all the time.
There were only three studies available and all three were small and at high risk of bias. We therefore judged the quality of the evidence to be very low, which means that we are uncertain how reliable the evidence is. Two very different studies compared anabolic steroid versus control (no anabolic steroid or placebo). One study conducted in the hospital ward compared weekly anabolic steroid injections versus placebo injections in 29 "frail elderly females". This study found no evidence that anabolic steroid resulted in better function, as measured by numbers discharged to a higher level of care or dead, or the time to mobilisation. The second study compared steroid injections given every three weeks for six months plus daily protein supplementation versus daily protein supplementation alone in 40 "lean elderly women". This study provided some evidence that anabolic steroids may result in better function, but they may also make no difference or result in worse function. Neither study found a difference in the incidence of individual adverse events in the two groups. Two studies compared anabolic steroids combined with another nutritional intervention ('steroid plus') versus control (no 'steroid plus'). One study compared anabolic steroid injections every three weeks for 12 months in combination with daily supplement of vitamin D and calcium versus calcium only in 63 women who were living independently at home. The other study compared anabolic steroid injections every three weeks for six months and daily protein supplementation versus control in 40 "lean elderly women". Both studies found some evidence of better function in the steroid plus group. Pooled mortality data from the two studies showed no difference between the two groups at one year. Similarly, there was no evidence of between-group differences in individual adverse events. Three participants in the steroid group of one study reported side effects of hoarseness and increased facial hair. The other study reported better quality of life in the steroid plus group. None of the studies reported on patient acceptability of the intervention. The quality of the evidence was very low, meaning that we are very uncertain about the direction and size of effect. Thus we are unable to say if anabolic steroids, either separately or in combination with nutritional supplements, improve recovery after hip fracture surgery in older people. Given that the results available point to the potential for more promising outcomes with a combined anabolic steroid and nutritional supplement intervention, we suggest that future research should focus on evaluating this combination.
We included 83 systematic reviews with evidence about whether or not the intervention was able to reduce pregnant women's chance of having a preterm birth or a baby death. Seventy of these reviews had information about preterm birth. We categorised the evidence we found as: clear benefit or harm; no effect; possible benefit or harm; or unknown effect. Clear benefit We were confident that the following interventions were able to help specific populations of pregnant women avoid giving birth early: midwife-led continuity models of care versus other models of care for all women; screening for lower genital tract infections; and zinc supplementation for pregnant women without systemic illness. Cervical stitch (cerclage) was of benefit only for women at high risk of preterm birth and with singleton pregnancy. Clear harm We found no treatment that increased women’s chance of giving birth preterm. Possible benefit The following interventions may have helped some groups of pregnant women avoid preterm birth, but we have less confidence in these results: group antenatal care for all pregnant women; antibiotics for pregnant women with asymptomatic bacteriuria; pharmacological interventions for smoking cessation; and vitamin D supplements alone for women without health problems. Possible harm We found two interventions that may have made things worse for some pregnant women: intramuscular progesterone for women at high risk of preterm birth with multiple pregnancy; and taking vitamin D supplements, calcium and other minerals for pregnant women without health problems. Clear benefit We were confident in evidence for midwife-led continuity models of care for all pregnant women; and for fetal and umbilical Doppler for high-risk pregnant women; these interventions appeared to reduce women's chance of experiencing baby death. Clear harm We found no intervention that increased women’s risk of baby death. Possible benefit We found a possible benefit with cervical stitch (cerclage) for women with singleton pregnancy and high risk of preterm birth. Possible harm One review reported possible harm associated with having fewer antenatal visits, even for pregnant women at low risk of pregnancy problems. The pregnant women in this review already received limited antenatal care. Unknown benefit or harm For pregnant women at high risk of preterm birth for any reason including multiple pregnancy, home uterine monitoring was of unknown benefit or harm. For high-risk pregnant women with multiple pregnancy: bedrest, prophylactic oral betamimetics, vaginal progesterone and cervical cerclage were all of unknown benefit or harm. There is valuable information in the Cochrane Library relevant to women, doctors, midwives and researchers interested in preventing early birth. We have summarised the results of systematic reviews to describe how well different strategies work to prevent early birth and baby death. We organised our information in clear figures with graphic icons to represent how confident we were in the results and to point readers toward promising treatments for specific groups of pregnant women. Our overview found no up-to-date information in the Cochrane Library for the important treatments of cervical pessary, vaginal progesterone or cervical assessment with ultrasound. We found no high-quality evidence relevant to women at high risk of preterm birth due to multiple pregnancy. It remains important for pregnant women and their healthcare providers to carefully consider whether specific strategies to prevent preterm birth will be of benefit for individual women, or for specific populations of women.
This review found that a single dose administered rectally was effective in relieving migraine headache pain and functional disability. Pain was reduced from moderate or severe to no pain by two hours in approximately 2 in 5 people (41%) taking sumatriptan 25 mg, compared with about 1 in 6 (17%) taking placebo. Pain was reduced from moderate or severe to no worse than mild pain by two hours in roughly 2 in 3 people (71%) taking sumatriptan 25 mg, compared with approximately 1 in 3 (30%) taking placebo. In addition to relieving headache pain, sumatriptan 25 mg also relieved functional disability by two hours in about 2 in 5 people (41%), compared with about 1 in 6 (16%) taking placebo. There was not enough evidence to draw any conclusions about the incidence of adverse events or to compare rectal sumatriptan directly with any other active comparators.
Miscarriage is the premature, or loss of a fetus, up to 23 weeks of pregnancy. Some women suffer from anxiety and depression after miscarriage which may be part of their grief following the loss. Psychological follow-up might detect those women who are at risk of psychological complications following miscarriage. This review of six studies, involving 1001 women, found that there is insufficient evidence from randomised controlled trials to recommend any method of psychological follow-up. Timing of the counselling interventions varied from one week following miscarriage up to 11 weeks. In all studies the interventions were delivered by different professional groups including a midwife, psychologists and nurses. Measurements of the outcomes were made from one month to 12 months after miscarriage in the different studies, which highlights the uncertainty surrounding the rate of psychological recovery following miscarriage. The two larger studies included a complex combination of interventions and outcome measures so that any potentially significant effects may have been diluted. Further robust research is needed to determine if any recognised psychological follow-up is effective is hastening psychological recovery following miscarriage.
The present review shows that there are few studies comparing alternative modes of exercise training to the standard of supervised walking exercise. The review authors identified five studies that randomised a total of 135 participants. The alternative modes of exercise therapy included cycling, strength training, and upper-arm ergometry. Comparing these alternative modes of exercise with supervised walking exercise showed no clear evidence of a difference in maximum or pain-free walking distance between the groups. Quality of life measures showed significant improvements in both groups; however, we could not make a direct comparison because of limited data. This review shows that alternative modes of exercise therapy seem to yield similar results to supervised walking therapy. Therefore, they may be considered useful when supervised walking exercise is not an option for the patient. However, more randomised controlled trials are needed to make a meaningful comparison between the different modes of exercise therapy.
This review identified 14 randomised controlled trials of radiotherapy for wet AMD. Most of these trials showed effects (not always significant) that favoured treatment with radiotherapy to prevent vision loss. However, overall this review does not provide convincing evidence that radiotherapy is an effective treatment for wet AMD, in part because the results of different trials were inconsistent, but also because it is possible that the treatment effects could be explained by the fact that it was not possible to mask the participants, and people measuring outcome, to the treatment group. The incidence of adverse effects reported in these trials was low - nobody developed any radiation-specific side effects although in three trials higher rates of cataract were reported in the radiotherapy group.
We searched the literature until November 2013. We included in the review 69 trials that randomly assigned 7863 participants . Participants were hospitalized with urinary tract, intra-abdominal, skin and soft tissue infections, pneumonia and infections of unknown source. One set of studies compared a broad-spectrum beta lactam versus a different, generally narrower-spectrum beta lactam combined with an aminoglycoside (47 studies). No clear difference in all-cause deaths was observed, but treatment failures were fewer with single beta lactam antibiotic treatment. A significant survival advantage was seen with single therapy in studies that involved infections of unknown source. The other studies compared one beta lactam versus the same beta lactam combined with an aminoglycoside antibiotic (22 studies). In these trials, no differences between single and combination antibiotic treatments were seen. Overall, adverse event rates did not differ between the study groups, but renal damage was more frequent with the combination therapy. Combination therapy did not prevent the development of secondary infection. The review authors concluded that beta lactam-aminoglycoside combination therapy does not provide an advantage over beta lactams alone. Furthermore, combination therapy was associated with an increased risk of renal damage. The limited number of trials comparing the same beta lactam in both study arms and the fact that more than a third of the studies did not report on all-cause deaths may limit these conclusions. The subgroup of Pseudomonas aeruginosa infections was underpowered to examine effects.
We found four studies with a total of 746 adult men and women undergoing abdominal surgery for removal of cancer. All studies were reanalyses of previously conducted trials, which means that none of the included studies was actually designed to investigate tumour recurrence. All patients underwent primary cancer surgery, which means that surgery on cancer metastases was not included. A total of 354 participants received general anaesthesia and 392 participants received a general anaesthesia along with an epidural anaesthesia. Epidural anaesthesia is a certain type of regional anaesthesia by which a numbing medication is injected continuously via a catheter into the epidural space. The epidural space serves as the outermost surrounding of the spinal cord. Numbing medication injected into the epidural space causes certain parts of the belly area to go numb and be insensitive to pain. Study participants were followed for at least 7.8 years after they had undergone cancer surgery. We did not find a benefit for either study group on cancer recurrence or survival. Because of incomplete reporting and the low number of reported adverse events, we cannot estimate possible differences in adverse effects between the different anaesthesia techniques used. The quality of the evidence for outcomes was graded low for overall survival and very low for progression-free survival and time to tumour progression. The main limitations of the evidence we identified were that the results could have been influenced by the background treatments given to people who participated in the trials.
No randomised controlled trials have examined this topic. Randomised controlled trials are the best studies for finding out whether one treatment is better or worse than another because they ensure that similar types of people are receiving the treatments being assessed. In the absence of randomised controlled trials, we sought information from non-randomised studies. We identified 12 non-randomised studies that compared laparoscopic versus open distal pancreatectomy in a total of 1576 patients. One of these studies did not provide results in a useable way. Thus, we included 11 studies in which a total of 1506 patients underwent distal pancreatectomy. Some 353 patients underwent laparoscopic distal pancreatectomy, and 1153 patients underwent open distal pancreatectomy. In all studies, historical information was collected from hospital records (retrospective studies). In general, historical information is less reliable than newly collected (prospective) information and findings of randomised controlled trials. Differences in short-term deaths, long-term deaths, percentage of people with major complications, percentage of people with a pancreatic fistula (abnormal communication between the pancreas and other organs or the skin), recurrence of cancer at final time of follow-up of participants, percentage of people with any complications and percentage of patients in whom cancer was not completely removed were imprecise. Average length of hospital stay was shorter in the laparoscopic group than in the open group by about two days. However, this is not relevant until we can be sure that cancer cures are similar between laparoscopic surgery and open surgery. No studies have reported quality of life at any point in time, short-term recurrence of cancer, time to return to normal activity, time to return to work or blood transfusion requirements. The quality of the evidence was very low, mainly because it was not clear whether similar types of participants received laparoscopic and open distal pancreatectomy. In many studies, people with less extensive cancer received laparoscopic surgery, and those with more extensive cancer received open surgery. This makes study findings unreliable. Well-designed randomised controlled trials are necessary if we are to obtain good quality evidence on this topic.
We included seven small studies with a total of 384 people with non-specific LBP of varying durations. Three studies (168 people) separately showed that LLLT was more effective at reducing pain in the short-term (less than three months), and intermediate-term (six months) than sham (fake) laser. However, the strength and number of treatments were varied and the amount of the pain reduction was small. Three studies (102 people) separately reported that LLLT with exercise was not better than exercise alone or exercise plus sham in short-term pain reduction. One study (56 people) showed that LLLT was more effective than sham at reducing disability in the short term. Three studies (102 people) compared LLLT plus exercise with exercise plus sham or exercise alone and did not show significant reduction in disability. Two studies (90 people) separately reported that LLLT was not more effective at reducing disability than exercise alone or exercise plus sham in the short-term. Based on these small trials, with different populations, LLLT doses and comparison groups, there are insufficient data to either support or refute the effectiveness of LLLT for the treatment of LBP. We were unable to determine optimal dose, application techniques or length of treatment with the available evidence. Larger trials that look specifically at these questions are required.
This review examined five randomised controlled trials, comprising a total of 208 participants with basilar skull fracture, which compared those who received preventive antibiotic therapy with those who did not receive antibiotics, to establish how many participants developed meningitis. The evidence is current to June 2014. The available data did not support the use of prophylactic antibiotics, as there is no proven benefit of such therapy. There was a possible adverse effect of increased susceptibility to infection with more pathogenic (disease-causing) organisms. We suggest that research is needed to address this question, as there are too few studies available on this subject and they have overall design shortcomings and small combined numbers of participants studied. We ranked the evidence as being of moderate quality because it is based on randomised data, although with some methodological limitations in design that caused us to downgrade the quality of the trials.
We identified 11 new trials on interventions for women in September 2015. We excluded one trial that was included in the earlier version of this review because it assessed treatment for preventing sexual dysfunction and was no longer relevant to this review. Interventions differed in their content and how the researchers measured benefit. Eight of the interventions involved psychological support such as counselling on sexual matters, or peer support. One of the others was of a testosterone cream, another tested a vaginal pH-balanced gel and the other was of pelvic floor exercise. The findings from six of the trials are weak because they involved small numbers of women. Across the trials the impact on sexual function was different. This makes it difficult to derive clear conclusions. For instance, in those that evaluated a psychological support treatment, four studies found that it improved some measures of sexual function but not others, but five found that it did not improve sexual function according to any of the measures used. For the other interventions tested, only the trial of the vaginal gel found improvements in sexual function and no side effects were reported. Only one of the psychological interventions reported that no harm occurred because of the intervention. The other trials of psychological support did not assess harm. This is an important gap as some women may find it distressing to discuss personal sexual problems as part of their treatment. Further evaluations are needed for all interventions. Current studies have only explored effectiveness in women with gynaecological and breast cancers, but there is a risk of sexual problems after treatments for other cancers. New evaluations need to involve larger numbers of participants.
We conducted the search for studies on 3 August 2015. We found four randomized controlled trials (RCTs) of surgical treatment for DVD. We found no studies evaluating non-surgical treatments. One trial was conducted in Canada and compared a surgical repositioning procedure (anteriorization of the inferior oblique muscle) with or without resection; one in the USA compared surgical weakening of an eye muscle (superior rectus recession) with or without augmentation with a fixation suture; and two in the Czech Republic compared anteriorization of the inferior oblique muscle versus removal of a piece of the inferior oblique muscle (myectomy). Only one of the RCTs examined what we wanted to know: the proportion of participants who had surgical success. There was insufficient information available to determine the differences between any of the surgical procedures with respect to surgical success or any other outcome relevant to our review. The most common adverse events from the surgical procedures were downward drifting of the eye after surgery (hypotropia), limited upward movement of the eye, and need for repeat surgery. All four of the included studies had flaws in design, execution, or both that weaken their conclusions. There is a need for well-designed, rigorously conducted RCTs of treatments for DVD to provide more reliable evidence for the management of this condition.
We searched relevant databases up to 25 March 2018. We found two clinical trials with a total of 85 participants with either single or solitary brain metastasis. One trial included 64 participants with a single brain metastasis, and the other included participants with a solitary brain metastasis (22 of these consented to randomisation and 21 were analysed). Both studies were prematurely closed due to difficulties in finding participants meeting the inclusion criteria or agreeing to participate. One trial compared surgery plus whole brain radiotherapy (WBRT) versus stereotactic radiosurgery alone, and the second trial compared surgery plus WBRT versus stereotactic radiosurgery plus WBRT. Due to the small number of people included in the studies, neither study had sufficient power to detect differences in the effects of surgery versus stereotactic radiotherapy on overall survival, adverse events, progression-free survival or quality of life in participants with single or solitary brain metastasis. The certainty of the evidence was low or very low mainly because of imprecision and risk of bias since the number of people in each trial was very small and participants and researchers were aware of the trial intervention (not blinded studies), so this could have affected how the participants evaluated outcomes, such as some adverse events and quality of life. Even though blinding of participants is difficult due to the nature of the intervention, study authors did not mention other ways of reducing the risk of bias, such as blinding during data analysis.
There was little evidence on the effectiveness and safety of most non-opioid drugs. However, evidence from single trials or at most two trials, suggests that some non-opioid drugs may work in providing pain relief. Non-opioid drugs were found to offer better pain relief (sedatives: one trial, 50 women), better satisfaction with pain relief (sedatives and antihistamines: two trials, 204 women; one trial, 223 women respectively) and better satisfaction with the childbirth experience (sedatives: one trial, 40 women) when compared with placebo. Women taking non-opioid drugs (NSAIDs or antihistamines) were less likely to be satisfied with pain relief when compared with women receiving opioids (one trial, 76 women; one trial 223 women). Women having the antihistamine hydroxyzine were more satisfied with their pain relief than those taking the antihistamine promethazine (one trial, 289 women) and women having sedatives were more satisfied with their pain relief than those having antihistamines. There were little data and no evidence of a significant difference for any of the comparisons of non-opioids for safety outcomes. The majority of studies were conducted over 30 years ago and the quality of all studies was questionable. No study used paracetamol.
This Cochrane Review summarizes trials that evaluated the benefits and potential risks of providing deworming drugs (antihelminthics) to people infected with human immunodeficiency virus (HIV). After we searched for relevant trials up to 29 September 2015 we included eight trials that enrolled 1612 participants. What are deworming drugs and why might they delay HIV disease progression Deworming drugs are used to treat a variety of human helminth infections, such as soil-transmitted helminths, schistosomiasis, onchocerciasis, and lymphatic filariasis. In areas where these infections are common, the World Health Organization currently recommends that targeted populations are routinely treated every six to 12 months without prior confirmation of an individual's infection status. The use of empiric therapy, or treating all at-risk populations presumptively, is preferred to test-and-treat strategies because deworming drugs are inexpensive and well tolerated. Additionally, a strategy of testing before treatment is considered less cost-effective given that available diagnostic tests are relatively expensive and can exhibit poor sensitivity. Helminth infections are known to affect the human immune system. In people with HIV, some studies have suggested that helminth infections may reduce the number of CD4+ cells (which are a critical part of the immune response to HIV) and compromise a person's ability to control HIV viral replication. Thus, treatment of helminth infections could have important benefits for people living with HIV beyond the benefits observed in the general population as a result of deworming. What the evidence in this review suggests Treating all HIV-positive adults with deworming drugs without knowledge of their helminth infection status may have a small suppressive effect on viral load at six weeks (low quality evidence), but repeated dosing over two years appears to have little or no effect on either viral load (moderate quality evidence) or CD4+ cell count (low quality evidence). These findings are based on two included studies. Providing deworming drugs to HIV-positive adults with diagnosed helminth infection may result in a small suppressive effect on mean viral load at six to 12 weeks (low quality evidence) and a small favourable effect on mean CD4+ cell count at 12 weeks (low quality evidence). However, these findings are based on small studies and are strongly influenced by a single study of praziquantel for schistosomiasis. Further studies from different settings and populations are needed for confirmation. Adverse events were not well reported (very low quality evidence), and trials were too small to evaluate the effects on mortality (low quality evidence). However there is no suggestion that deworming drugs are harmful for HIV-positive individuals.
We found 16 studies including over 1700 people with COPD who experienced a flare-up that required additional medical treatment that compared corticosteroid given by injections or tablets with dummy treatment. Four studies with nearly 300 people compared corticosteroid injections with corticosteroid tablets. More men than women took part in the studies and they were usually in their late 60s, with moderately severe symptoms of COPD. Most studies took place in hospitals, two in intensive care units with people who needed breathing support, and three studies involved people who were treated at home. The last search for studies to include in the review was done in May 2014. There were three studies where people knew which treatment they were getting, but otherwise studies were generally well designed. People treated with either corticosteroid injections or tablets compared with dummy treatment were less likely to experience treatment failure, 122 fewer people per 1000 treated, with a lower rate of relapse by one month. They had shorter stays in hospital if they did not require assisted ventilation in an intensive care unit, and their lung function and breathlessness improved more quickly during treatment. However, they had more adverse events while taking treatment, especially a temporary increase in glucose levels in blood. Corticosteroid treatment did not reduce the number of people who died within one month of their flare-up. In studies comparing two ways of giving corticosteroid, either by injections or tablets, there were no differences in treatment failure, the time in hospital or number of deaths after discharge; however, a temporary increase in glucose levels in blood was more likely with injections than tablets. There is high-quality evidence that is unlikely to be changed by future research that people who experience flare-ups of COPD benefit from treatment with corticosteroid given by injections or tablets with the increased risk of some temporary side effects.
we searched for studies that had been published up to 1 August 2019. We identified three randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) involving 114 adults (228 eyes) from three countries (New Zealand, Japan and China) that had been published between 2015 and 2019. The maximum time that people in the studies were followed up for after the treatment was nine months. because of very low-quality evidence, we are unclear about the effect of IPL on dry eye symptoms. IPL may be helpful to improve some of the clinical signs of MGD (such as tear stability and tear composition - both signs of how healthy the tears produced by the eye are). We are uncertain about the effect of IPL on meibomian gland blockage or corneal sodium fluorescein staining. As most studies did not report side effects, we are uncertain about the safety of IPL as a treatment for MGD. Very low-quality results from individual studies suggest there may be some side effects, including mild eye pain and burning, and partially losing eyelashes (due to mistakes when using the IPL device). the evidence for how effective and safe IPL is for treating MGD was of low or very low quality. due to limited information in the clinical trials, we could not determine with certainty whether IPL treatment for MGD is effective or safe. The review findings indicate that more research is needed. It is important that eye care clinicians, and people considering having IPL as a dry eye treatment, are aware that there is limited high-quality research to understand whether the procedure is effective or safe.
The researchers found three studies with a total of 714 adult (> 18 years) participants. These participants all had moderate to severely active Crohn's disease. A total of 451 participants were treated with adalimumab and 268 were treated with a placebo (a fake medication). More participants who were treated with adalimumab achieved remission or improvement of their symptoms than those who were treated with placebo. The rates of side effects (adalimumab: 62%, placebo: 72%), serious side effects (adalimumab: 2%, placebo: 5%) and study withdrawal due to side effects (adalimumab: 1%, placebo: 3%) were lower in adalimumab participants than placebo participants. Commonly reported side effects included injection site reactions, abdominal pain, fatigue, worsening Crohn's disease and nausea. High-certainty evidence suggests that treating participants with adalimumab is better than treating them with placebo for inducing remission and improving symptoms in people with moderate to severely active Crohn's disease. Side effects were lower in adalimumab participants compared to placebo. However, we are uncertain about the effect of adalimumab on side effects due to the low number of events, therefore, no firm conclusions can be drawn regarding the harms (side effects) of adalimumab in Crohn's disease. Futher studies are required to look at the long-term benefits and harms of using adalimumab in people with Crohn's disease.
This review found no significant effect of glucocorticosteroids on chronic hepatitis, but the amount of data is sparse. Accordingly there is insufficient evidence to neither confirm nor exclude beneficial and harmful effects of glucocorticosteroids for hepatitis C. Further, the evidence is unclear as to whether glucocorticosteroids treatment can be safely administered for other diseases in patients with concomitant hepatitis C. The authors were unable to identify randomised clinical trials on glucocorticosteroids for acute hepatitis C.
The review authors searched the medical literature in order to clarify the role of RFA for the treatment of hepatocellular carcinoma and to compare its benefits and harms with no treatment, placebo (a pretend treatment), or other treatments (such as hepatic resection, percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), laser or microwave ablation, and liver transplantation). We looked for randomised clinical trials (where people were allocated at random to one of two or more treatments groups) of people with hepatocellular carcinoma who were able to receive RFA. Evidence is current to September 2013. We found no trials comparing RFA versus no intervention, placebo, chemotherapy, or liver transplantation. The review authors found moderate-quality evidence from two trials with low risk of bias (where there was a low risk of a flaw in study design, method of collecting or interpreting results) randomising 578 patients suggesting that hepatic resection yielded better results regarding overall survival (the length of time that the patient remains alive), event-free survival (time that the person remains free of cancer or a certain symptom relating to cancer), and progression (time that the patient lives with cancer without it getting worse) compared with RFA. However, as resection is a more invasive procedure, resection has an eight times higher risk of major complications compared with RFA. Resected patients stayed twice as long in the hospital as the RFA patients. Moderate-quality evidence suggested that RFA prolongs survival and decreases recurrences (where the cancer returns) compared with PEI or PAI. This conclusion was based on data from six randomised clinical trials with 1088 participants. Some patients developed side effects such as fever, rash, and pain. These occurred at the same frequency in both treatment groups. We calculated the number of patients that would be required to judge a relative risk reduction (relative risk is a comparison of the risk of an event happening for one treatment group compared with another treatment group) for survival of 20%. The review authors found that for both comparisons, that is RFA versus PEI or PAI, and RFA versus resection, the number of patients in the included trials was too low to reach valid conclusions. No firm conclusion can be drawn from the comparison of RFA against other interventional techniques or combination approaches. The information provided by the single trials was limited. More randomised clinical trials with low risks of bias (that is low risks of systematic errors, leading to overestimation of benefits and underestimation of harms) and low risk of play of chance (that is random errors, leading to overestimation or underestimation of benefits and harms) are required.
We identified eight studies with 1083 participants comparing probiotics versus placebo for preventing VAP. The studies were conducted between 2006 and 2011 in China, France, Greece, Slovenia, Sweden, the UK and the USA, with funding from various sources including hospital/National Health Service, pharmaceuticals and the National Institutes of Health. In the studies that stated the gender ratios, there were 611 males and 378 females. The evidence is current to September 2014. The results from these trials show that probiotics are associated with a reduction in instances of VAP. However, the quality of the evidence is low and the exclusion of the one study that did not provide a robust definition of VAP increased the uncertainty in this finding. Results for all remaining reported outcomes (including mortality, incidence of diarrhoea, length of ICU stay, duration of mechanical ventilation and general antibiotic use) were uncertain between groups receiving either probiotics or placebo or standard treatment. Incidence of diarrhoea was reported in half of the included studies, which demonstrated no clear evidence of a difference between probiotics over standard care or placebo. The quality of the evidence was generally low to very low between studies. Due to the contradictions in the results from previously published systematic reviews and the uncertainty of these results, there is need for larger, well-designed and robustly reported studies.
The evidence is current to November 2013. We included six studies involving 126 participants who completed the study protocols. Most studies recruited participants with severe to very severe COPD. The average age of participants ranged from 63 to 71 years. Cycling or treadmill exercise training was performed in the studies. The duration of exercise training programmes ranged from six to twelve weeks. The percentage change in peak exercise capacity increased by an average of 17% in three studies, and the percentage change in endurance exercise capacity by an average of 59% in two studies that provided NIV during training compared with training without NIV or training with sham NIV. However, these improvements in exercise capacity were not consistent findings as there was no clear evidence that NIV improved all other measures of exercise capacity. The results for quality of life were uncertain and our analysis did not exclude there being an effect with NIV during exercise training in two studies. Physical activity was not assessed in any of the studies. Non-invasive ventilation allowed participants to exercise at a higher training intensity (average of 13% higher) in three studies, and evidence of a greater training effect on the muscles was found in two studies, as a marker in the blood (isoload blood lactate) was significantly lower by an average of 0.97 mmol/L. No information regarding adverse events or cost was reported. It is currently unknown whether demonstrated benefits of NIV during exercise training are clinically worthwhile or cost-effective. This review was generally limited by the small number of included studies and the small numbers of participants within the included studies. The quality of the evidence was low for exercise capacity outcomes, largely because of issues with study design. Consequently, the effect of NIV during exercise training on exercise capacity is uncertain. The quality of the evidence for quality of life, training intensity and isoload blood lactate was moderate, and these findings can be interpreted with a greater degree of confidence.
We aimed to find out which was the better way to keep a newborn baby's intravenous line open and working -- either running a continuous amount of intravenous fluid through it (continuous infusion) or giving a small amount of fluid through it every few hours (intermittent flush) only. One study showed no difference between the two approaches for keeping a baby's intravenous line open and working and one study showed an advantage for intermittent flushes. The studies, however, had some problems in how the data were analysed and reported. Therefore, we are uncertain as to how reliable the results are and further research should be undertaken.
We included in this updated review 14 trials with 1275 participants. We found the overall quality of trials to be moderate, with little information provided on how experiments were carried out. Results were limited, and most included trials were small. In most trials, we identified risk of misleading information. Thus, results must be interpreted with caution. The evidence is up-to-date to 18 November 2015. No strong evidence is available to support the use of INO to improve survival of adults and children with acute respiratory failure and low blood oxygen levels. In the present systematic review, we set out to assess the benefits and harms of its use in adults and children with acute respiratory failure. We identified 14 randomized trials comparing INO versus placebo or no intervention. We found no beneficial effects: despite signs of oxygenation and initial improvement, INO does not appear to improve survival and might be hazardous, as it may cause kidney function impairment.
This review included 11 randomised or quasi-randomised trials. The majority of the participants were female, usually aged around 80 years. There were seven comparisons but the evidence for each of these was insufficient to draw conclusions. Thus, the review found that there was too little evidence from randomised trials to show which, if any, specific surgical techniques used during operations for extracapsular proximal femoral fractures are better.
Only one trial evaluated rectal artesunate as pre-referral treatment. In the African sites only, children aged 6 to 72 months were included in the trial; while in the Asian trial site, older children and adults were included. Young children in the African and Asian trial sites (aged 6 to 72 months) had fewer deaths with rectal artesunate than with placebo (moderate quality evidence). However, in Asia among older children and adults, there were more deaths in those that received rectal artesunate (low quality evidence). In the African sites, 56% of children took longer than six hours to reach hospital whereas over 90% of people in the Asian site reached hospital within six hours. The unexpected finding of more deaths with rectal artesunate in older children and adults should be taken into account when forming national and local policies about pre-referral treatment.
Forty three trials involving 3957 women were included. The review compared different drugs for ovarian hyperstimulation showing that injections result in higher pregnancy rates compared with oral medication. However, the evidence for this result is not very strong. Furthermore, it showed that if stimulation is used it might be done with low dose injections, since multiple pregnancy rates were increased with high dose injections, without resulting in more pregnancies. This review does not show which injection should be used, since there is no convincing evidence of a difference. Finally, this review does not answer the question whether the addition of GnRH agonist or antagonist is useful.
The Information Specialist from Cochrane Schizophrenia ran electronic searches of the group's specialised register (the most recent in February 2019) for trials that randomised people with catatonia occurring in conjunction with schizophrenia or other similar serious mental illnesses to receive either benzodiazepines or any of the following: other drugs, placebo, or electroconvulsive therapy. One hundred and thirty records were found and checked by the review authors. One trial was found in the search which met the review requirements and provided limited, very low quality usable data for one outcome only. This trial compared two benzodiazepines (lorazepam vs oxazepam) and found no clear difference between these two treatments for improvement in the symptoms of catatonia for people who have catatonia and schizophrenia or similar serious mental illness. There is insufficient high quality evidence available to answer the review question. More high quality research is needed.
We included 19 trials (18 publications) that involved 5835 people. Trials studied different antibiotics for people with sore throat who tested positive for GABHS, and were aged from one month to 80 years. Nine trials included only children; and nine included people aged 12 years or older. Most studies were published over 15 years ago; all but one reported on clinical outcomes. Thirteen trials were supported by drug study funding - some received grants - others included people employed by drug companies. Five studies did not report funding. Antibiotic effects were similar, and all caused side effects (such as nausea and vomiting, rash), but there was no strong evidence to show meaningful differences between antibiotics. Studies did not report on long-term complications so it was unclear if any class of antibiotics was better in preventing serious but rare complications. All studies were in high-income countries with low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities where risk remains high. Our review supports the use of penicillin as a first choice antibiotic in patients with throat infections caused by GABHS. Evidence quality was low or very low for all outcomes when macrolides or cephalosporins were compared with penicillin. Evidence quality was downgraded because of concerns about randomisation and blinding, wide confidence intervals (estimates were not very precise) and statistical differences among studies that may impact on the validity of the estimate. Most study authors did not report enough information about methods to be sure there was no bias.
This systematic review evaluated the efficacy and tolerability of pregabalin in people with epilepsy. The review authors only included two, short-term randomised controlled trials involving 753 participants treated with pregabalin monotherapy for epilepsy. Studies included in this review suggested that pregabalin was inferior to lamotrigine but was better than gabapentin, but we found some limitations in the study design which may have had a great influence on the results. There is no strong evidence to support its monotherapy as a treatment for epilepsy. Long-term trials and high quality randomised clinical trials are needed to evaluate the efficacy and safety of pregabalin monotherapy for treating epilepsy.
Existing research studies are too small and methodologically flawed to allow us to draw strong conclusions; on the basis of existing evidence it is not clear whether hair removal pre-operatively affects rates of surgical site infections. However if hair has to be removed to facilitate surgery or the application of adhesive dressings, clipping rather than shaving appears to result in fewer surgical site infections.
We searched the medical literature for studies that compared different types of products that are used to keep PVCs in place. We found six studies (involving 1539 participants) that compared four different ways of securing PVCs. These included: 1. a plain transparent film dressing compared with a gauze (woven fabric) dressing; 2. a bordered transparent dressing (clear transparent window with a reinforced fabric edge) compared with a securement device (that has anchor points or clips that hold the PVC in place over a strong adhesive base pad on the skin) that is used in conjunction with a transparent film dressing; 3. a bordered transparent dressing compared with non-sterile medical tape; 4. a plain transparent film dressing compared with sticking plaster. The participants in the studies were both adults and children on medical and surgical wards. There were no studies based in emergency departments. Two studies provided very low quality evidence that PVCs were less likely to fail when a transparent dressing was used rather than gauze. Other positive outcomes favouring one dressing over another were based on the results of very low quality, single studies. Overall there is a lack of high quality evidence and continued uncertainty regarding the best methods of securing a peripheral venous catheter remains. More high quality research is needed in this area. We assessed a number of quality indicators regarding the methods used in each study and graded the overall quality of studies as very low. Each study had a high or unclear risk of bias for some of the quality indicators. For example, it is likely that clinical staff responsible for assessing participants' outcomes knew the treatment group to which each person belonged, as the securement methods for PVCs looked different. There were only a limited number of studies available for consideration in this review, and they did not investigate some securement products that are in common use.
Oral herbal medications may reduce neck pain more than placebo and Jingfukang. A topical herbal medicine (Compound Extractum Nucis Vomicae) also relieved neck pain in the short term (four weeks), but the trail had a high risk of bias. All four included studies were in Chinese and two of these studies were unpublished. Half of the trials had a low risk of bias, but they only tested the effects of short term use (up to eight weeks). The size of the studies was small. There is a need for trials with adequate numbers of participants that address the long-term efficacy or effectiveness of Chinese herbal medicine compared to placebo. For chronic neck pain with or without radicular symptoms, there is low quality evidence that Compound Qishe Tablet is more effective than placebo for pain relief, measured at the end of the treatment. However, the size of the studies was small and the effect was measured in the short-term. Further research is very likely to change both the effect size and our confidence in the results. There is a need for trials with adequate numbers of participants that address long-term efficacy or effectiveness of herbal medicine compared to placebo.
We examined the evidence from 14 studies with 2616 participants with CKD not receiving dialysis published before 12 September 2016 to determine whether differences in improvement in anaemia and in side effects existed between different short-acting epoetins or between the same epoetins given at different frequencies. We did not find any studies using different frequencies of epoetins in children. We found that the traditionally shorter acting epoetins given less often (two weekly to every four weeks) resulted in similar correction of anaemia compared with administration every week or every two weeks; there were no differences in side effects between the different comparisons. One study comparing subcutaneous administration of a newly manufactured HX575 epoetin alpha compared with epoetin alpha was discontinued after two patients developed anti-erythropoietin antibodies. However more studies are required as most studies were small and poorly designed, which limits their application to the care of patients.
Four randomised controlled trials (RCTs) with 307 participants with IBS were included. Two RCTs (129 participants) compared a homeopathic remedy (asafoetida and asafoetida plus nux vomica) to a placebo remedy for the treatment of people with IBS-C. One study (23 participants) compared individualised homeopathic treatment to usual care in female patients diagnosed with IBS. One study (94 participants) was a three armed study comparing individualised homeopathic treatment plus usual care, supportive listening plus usual care and usual care. The four trials tested the effects of homeopathic treatment on the severity of IBS symptoms. No conclusions can be drawn from the RCT comparing individualised homeopathic treatment to usual care due to the small number of participants and the low quality of reporting in this trial. This study was carried out in 1990 and usual care for IBS may have changed since then making the results difficult to compare to current treatments. No conclusions can be drawn from the three armed study comparing individualised homeopathic treatment plus usual care, supportive listening plus usual care and usual care due to the small number of participants in the homeopathic treatment arm (n=16). The results of two small studies were combined (129 participants) and this suggested that there may be a possible benefit for clinical homeopathy, using the remedy asafoetida, over placebo for patients with IBS-C at a short-term follow-up of two weeks. However both of the studies were carried out in the 1970s when the reporting of trials was not as comprehensive as it is now and we are very uncertain about these results and cannot suggest a possible benefit for clinical homeopathy. The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the effectiveness and safety of homeopathy for the treatment of IBS can be drawn. Further high quality RCTs enrolling larger numbers of patients are required to assess the effectiveness and safety of clinical and individualised homeopathy for IBS.
This review was undertaken to determine the beneficial and harmful effects of vaccination against hepatitis B and of a reinforced recombinant vaccination series. None of the trials had high methodological quality. Plasma vaccine was significantly more effective than placebo in achieving hepatitis B antibodies. Yet no statistically significant difference was found between the use of plasma vaccine or placebo in preventing hepatitis B virus infections. No trials comparing recombinant vaccine with placebo were identified. There was no significant difference between recombinant and plasma vaccines or between a reinforced vaccination series and routine vaccinations of three inoculations using recombinant vaccine regarding achieving hepatitis B antibodies.
We looked for studies of psychological treatments in individuals of all ages with cystic fibrosis and their families which aimed to reduce anxiety and depression, to improve adjustment, quality of life, and even medical outcomes, as well as knowledge, skills, and decisions regarding care. The review includes 16 studies with a total of 556 participants. Even though there many different psychological interventions, only a few have been evaluated for individuals with CF and their families. Due to the lack of high quality studies, it is not possible to currently show which psychological treatments are most helpful to those with cystic fibrosis and their caregivers. Five out of the 16 studies we found evaluated behavioural interventions to improve dietary intake. We found that in children aged 4 to 12 years receiving a nutritional intervention plus behavioural management training, consumed about 276 per day more than children just receiving the nutritional intervention. We also found that a structured decision-making tool for adults considering lung transplantation improved their knowledge, assisted in setting realistic expectations, and reduced indecision. In summary, there is some evidence that behavioural interventions targeting specific illness-related symptoms and behaviours can work. More studies on psychological interventions with more people are urgently needed. There are several ongoing randomised controlled studies aimed at improving adherence to prescribed treatments, but final results are not yet available. We recommend multicentre studies to provide evidence for which interventions are most effective for the key issues faced by people with cystic fibrosis and their caregivers.
We identified 12 studies involving 478 individuals after stroke. Most used video sequences and AO followed by some form of physical activity, using a range of activities, with task complexity increased over the course of training or when it was easy for the participant to carry out. The evidence is current to October 2017. Studies tested whether the use of AO compared with an alternative intervention or no intervention resulted in participants' improved ability to use their arms and hands, and found that AO therapy resulted in better arm (eight trials) and hand function (three trials). We classified the quality of the evidence as moderate for hand function, low for arm function and dependence on activities of daily living, and very low for motor performance and quality of life. Participants could engage in AO safely, since adverse events were not significant in scale or magnitude. The quality of the evidence for each outcome was limited due to the small number of study participants, low study quality, and poor reporting of study details.
Seventy two randomised controlled trials met our inclusion criteria. The range of interventions used included (1) self-monitoring, (2) educational interventions directed to the patient, (3) educational interventions directed to the health professional, (4) health professional (nurse or pharmacist) led care, (5) organizational interventions that aimed to improve the delivery of care, (6) appointment reminder systems. The trials showed a wide variety of methodological quality, part of which may be attributed to poor reporting. An organized system of regular review allied to vigorous antihypertensive drug therapy was shown to reduce blood pressure and all-cause mortality in a single large RCT- the Hypertension Detection and Follow-Up study. Other interventions had variable effects. Weighted data analysis showed that self-monitoring was associated with moderate net reductions in systolic blood pressure (weighted mean difference -2.5 mmHg, 95% CI: -3.7 to -1.3 mmHg) and diastolic blood pressure (weighted mean difference -1.8 mmHg, 95% CI: -2.4 to -1.2 mmHg). Trials of educational interventions directed at patients or health professionals were heterogeneous but appeared unlikely to be associated with large net reductions in blood pressure by themselves. Nurse or pharmacist led care may be a promising way of improving control in patients with hypertension, with the majority of RCTs being associated with improved blood pressure control, improved systolic blood pressure and more modestly improved diastolic blood pressure, but these interventions require further evaluation. Appointment reminder systems increased the proportion of individuals who attended for follow-up (absolute difference 16%, but this pooled result should be treated with caution because of the heterogeneous results from individual RCTs) and in two small trials also led to improved blood pressure control, odds ratio favouring intervention 0.54 (95% CI 0.41 to 0.73). We conclude that an organized system of registration, recall and regular review allied to a vigorous stepped care approach to antihypertensive drug treatment appears the most likely way to improve the control of high blood pressure. Health professional (nurse or pharmacist) led care and appointment reminder systems requires further evaluation. Education alone, either to health professionals or patients, does not appear to be associated with large net reductions in blood pressure.
This review found 28 studies on five second-generation antipsychotic drugs (amisulpride, aripiprazole, olanzapine, quetiapine and risperidone) comparing the effects of the drugs alone or adding them or placebo to antidepressants for major depressive disorder and dysthymia. There is evidence that amisulpride might lead to symptom reduction in dysthymia, while no important differences were seen for major depression. There is limited evidence that aripiprazole leads to symptom reduction when added to antidepressants. Olanzapine had no beneficial effects for treatment of depression when compared to antidepressants or compared to placebo but there was limited evidence for the benefits of olanzapine as additional treatment. Data on quetiapine indicated beneficial effects for quetiapine alone or as additional treatment when compared to placebo; data on quetiapine versus duloxetine did not show beneficial effects in terms of symptom reduction for either group, but quetiapine treatment was less well tolerated. The data, however, are very limited. Slight benefits of risperidone as additional treatment, in terms of symptom reduction, are also based on a rather small number of randomised participants. Generally, treatment with second-generation antipsychotic drugs was associated with worse tolerability, mainly due to sedation, weight gain or laboratory values such as prolactin increase.
Authors from the Cochrane Oral Health Group carried out this review update of existing studies and the evidence is current up to 21 January 2014. It includes 15 studies published from 1984 to 2013. Nine of these studies compared fixed (always in the mouth) appliances either against different fixed appliances, or against the same fixed appliance but comparing different rates of expansion. Two studies compared a fixed appliance with a removable appliance. The remaining four studies evaluated other comparisons that were more difficult to classify. There is some evidence to suggest that the quad-helix (fixed) appliance may be more successful than removable expansion plates at correcting posterior crossbites and expanding the top back teeth for children with a mixture of baby and adult teeth (aged eight to 10 years). The remaining evidence we found did not allow the conclusion that any one treatment is better than another. The evidence presented is mostly of low to very low quality due to the small amount of available studies and issues with the way in which they were conducted.
This review is based upon three randomised controlled trials comparing RBL with EH, with a total of 216 patients. The trials showed that with EH, haemorrhoids did not come back as often as with RBL. EH was better for advanced haemorrhoids, known as grade III haemorrhoids. For less severe grade II haemorrhoids, RBL and EH were equally effective. EH caused more pain after the procedure, more minor complications, and required more time off work. Patient satisfaction was similar for both treatments. This review has been up dated as of October 2010 and the search was carried out with previously used search strategy to identify any possible new randomised controlled study to include in the statistics. Only one additional paper was identified with a potential possibility to include in the study (Ali 2005). However, after a combined common decision from all the authors, it was decided to exclude the paper for the statistics because of the poor data presentation and randomisation method.  After up to date search, the conclusion has not changed and the review authors conclude that RBL should be the primary treatment used for grade II haemorrhoids, and EH reserved for patients who failed after repeated RBL or grade III haemorrhoids. They recommend more research be done comparing these techniques with the many newer ones, especially stapled haemorrhoidopexy, to determine which treatment is best.
In February 2014, we updated the computer searches for studies of vasectomy methods. For the initial review, we also looked at reference lists of articles and book chapters. We included randomized controlled trials in any language. We found six studies. One trial compared closing the vas with clips versus the usual cutting of the vas. The groups did not differ in reaching a low sperm count or in side effects. Three trials looked at flushing fluids through the vas: two compared vasectomy with water flushing versus vasectomy alone, and one compared using water versus euflavine (which kills sperm). None found a difference between the groups in time to low sperm count. However, one trial found that the usual number of ejaculations before low sperm count was lower with euflavine than with water. One trial that compared vasectomy with and without fascial interposition was a high-quality large study. The fascial interposition group was less likely to have vasectomy failure. However, the surgery was more difficult. Side effects were about the same in the two groups. Lastly, one trial looked at a device placed into the vas versus vasectomy without a scalpel. The intra-vas device did not work as well for reaching a low sperm count but more men liked the method. Most of the studies that looked at vasectomy methods were small, not done well, or had poor reports. Therefore, we cannot say if the methods work well, are safe or are liked by men. Vasectomy with fascial interposition worked better than simply cutting and tying the vas, but the surgery was more difficult. More and better research is needed on vasectomy methods.
We included two studies that analysed a total of 103 participants. The evidence in this review is up to date as of 20 January 2017. Study participants were adults older than 16 years of age. One study compared titanium with resorbable plates and screws and the other titanium with resorbable screws. One study was conducted in China, the other in Germany. Both studies were at high risk of bias and provided very limited data. We do not have sufficient evidence to determine if titanium plates or resorbable plates are superior for the fixation of bones after corrective jaw surgery. This review provides insufficient evidence to show any difference in postoperative pain and discomfort, level of patient satisfaction, plate exposure or infection for plate and screw fixation using either titanium or resorbable materials. Both included studies were assessed as being at high risk of bias and the very limited and weak evidence was of very low quality.
We found 92 trials that randomly assigned participants to take either an ACE inhibitor or an inert substance (placebo). These trials evaluated the blood pressure lowering ability of 14 different ACE inhibitors in 12 954 participants. The trials followed participants for approximately 6 weeks (though people are typically expected to take anti-hypertension drugs for the rest of their lives). The blood pressure lowering effect was modest.  There was an 8-point reduction in the upper number that signifies the systolic pressure and a 5-point reduction in the lower number that signifies the diastolic pressure.  Most of the blood pressure lowering effect (about 70%) can be achieved with the lowest recommended dose of the drugs.  No ACE inhibitor drug appears to be any better or worse than others in terms of blood pressure lowering ability. Most of the trials in this review were funded by companies that make ACE inhibitors and serious adverse effects were not reported by the authors of many of these trials.  This could mean that the drug companies are withholding unfavorable findings related to their drugs.  Due to incomplete reporting of  the number of participants who dropped out of the trials due to adverse drug reactions, as well as the short duration of these trials, this review could not provide a good estimate of the harms associated with this class of drugs.  Prescribing the least expensive ACE inhibitor in lower doses will lead to substantial cost savings, and possibly a reduction in dose-related adverse events.
We included six studies, which comprised two prevention trials (a total of 327 young to middle-aged adults in Russia) and four treatment trials (a total of 1196 teenagers and adults in France and Germany). The findings from the two prevention trials did not show that Oscillococcinum®can prevent the onset of flu. Although the results from the four other clinical trials suggested that Oscillococcinum®relieved flu symptoms at 48 hours, this might be due to bias in the trial methods. One patient reported headache after taking Oscillococcinum®. The evidence is current to September 2014. The overall standard of research reporting was poor, and thus many aspects of the trials' methods and results were at unclear risk of bias. We therefore judged the evidence overall as low quality, preventing clear conclusions from being made about Oscillococcinum®in the prevention or treatment of flu and flu-like illness.
This systematic review assesses the effects of studies that examined dietary advice with or without the addition of exercise or behavioural approaches. Eighteen studies were included. No data were found on micro- or macrovascular diabetic complications, mortality or quality of life. It is difficult to draw reliable conclusions from the limited data that are presented in this review, however, the addition of exercise to dietary advice showed improvement of metabolic control after six- and twelve-month follow-up.
Based on our latest search of the literature from November 2017, we included 64 studies with 10,509 participants. Of these, 15 studies compared alpha-blockers with placebo with 5787 participants. A placebo is a pill that looks and tastes exactly like the real medication, so participants did not know what they were getting. These were the higher-quality studies, which we trusted more. Based on the subset of higher-quality studies that used a placebo, alpha-blockers likely resulted in more people passing their stones. However, these patients are likely to experience slightly more serious unwanted effects of this medication. People taking alpha-blockers may pass their stones in a shorter time, may use less diclofenac (which is a type of pain medication), and are likely to be admitted to the hospital less often. Meanwhile, the need for surgery for their stones was similar. Upon completing additional analyses, we found that effects of alpha-blockers may be different in people with small (5 mm or smaller) versus larger (larger than 5 mm) stones. It appears that this medication works better in people with larger stones. We could find no difference in how well alpha-blockers work, no matter where in the ureter the stone is stuck or what type of alpha-blocker is used. For patients with stones stuck in the ureter, alpha-blockers likely make passing the stone easier but cause slightly more unwanted effects. It appears that alpha-blockers work better in people with larger (greater than 5 mm) rather than smaller (5 mm or smaller) stones. The quality of the evidence for most outcomes was moderate or low, meaning that we have moderate or low confidence in most of the reported results.
The evidence is current to December 2015. The current review identified one study,Santolaya 2004, in which early discharge was compared to non-early discharge in this group of children, and one study,Brack 2012, in which very early discharge was compared to early discharge. Early discharge did not appear to be less safe than non-early discharge in children with cancer and fever during neutropenia with a low risk for bacterial infections; there was no clear evidence of difference in treatment failure between the two groups. Moreover, the treatment costs in the early discharge group were lower than in the non-early discharge group. Regarding very early discharge, this did not appear to be less safe than early discharge; there was no clear evidence of difference in treatment failure between the two groups. Duration of treatment differed between very early discharge and early discharge; duration of intravenous antibiotic treatment was shorter in the very early discharge group, and duration of oral antibiotic treatment was shorter in the early discharge group, as compared to one another. However, there was no clear evidence of difference in total treatment duration of any antibiotic treatment between these groups. For both reported comparisons, the quality of the evidence was low. The included studies were relatively small with a low number of participants, thus it was possible that the absence of clear evidence of differences in the included studies could be due to, for example, the lack of power. Unfortunately, it was not possible to pool data in the two studies. In conclusion, regarding both rehospitalization or adjustment of antibiotics (or both) and death, evidence was fairly limited; however, there was no evidence that early discharge was less safe than non-early discharge or very early discharge was less safe than early discharge of children with cancer and fever during neutropenia and a low risk for invasive bacterial infection. Future larger trials are needed to confirm or contradict these results.
In this review, we compared atherectomy to the more established treatments such as balloon angioplasty and bypass surgery. We identified four studies with a total of 220 participants. All studies compared atherectomy with balloon angioplasty. The studies were of low quality as there was no blinding of the procedures, the studies were not properly powered to show an effect, not all study outcomes were reported and a large number of the initial study populations did not complete the studies. Although the results of the meta-analyses were imprecise, the average effect of the two treatments was similar in terms of initial success and unobstructed arteries (patency) at six months or 12 months following the procedure. There was a lower risk of death with atherectomy, most likely due to an unexpectedly high number of deaths in the balloon angioplasty group in one of the two trials reporting deaths. Cardiovascular events were not reported in any of the included studies. There was a reduction in the rate of emergency stenting procedures following atherectomy, and balloon inflation pressures were lower following atherectomy. Complications such as formation of clots (embolisation) and tears along the vessels (vessel dissection) were reported in two trials indicating more embolisations in the atherectomy group and more vessel dissections in the angioplasty group but the data could not be combined. The limited data available indicated that there was no clear evidence of a difference between the atherectomy and balloon angioplasty groups for adverse events such as the need for re-intervention due to obstruction of the treated vessel and above-knee amputation. Quality of life and clinical and symptomatic outcomes such as walking distance or symptom relief were not reported in the studies. We showed that the limited evidence available does not support a significant advantage of atherectomy over conventional balloon angioplasty.
Based on a search in 2011, this review includes four trials with a total of 607 people and evaluates the effects of user-held information for people with severe mental illness. In the main, the number of relevant studies is low, with poor reporting of some outcomes. Based on moderate quality evidence, the review found that user-held information did not decrease hospital admissions, and did not decrease compulsory admissions or encourage people with severe mental illness to attend appointments (when compared to treatment as usual). Other important outcomes, such as satisfaction with care, costs and effect on mental health, were not available due to the limited quality of the four studies. There is therefore a gap in knowledge and evidence regarding user-held information for people with severe mental health problems. Further evidence is also required on the different types of user-held information (for example, if it involves the mental health team and what type of information is included in the record). Large-scale, well-conducted and well-reported studies are required to assess the effects of user-held information for people with mental illness. Two important randomised studies are currently taking place. For the present, despite a gap in evidence, user-held information is low cost and acceptable to patients, so its use is likely to grow. However, it cannot be assumed that user-held information is of benefit to people and is cost-effective without further large-scale, well-conducted and well-reported trials. This plain language summary has been written by a consumer, Benjamin Gray: Rethink Mental Illness. E-mail: [email protected]
The present review looked at the available evidence for endovascular repair effectiveness compared with open surgery for ruptured aneurysms. We included four studies with a total of 868 participants. Risk of bias was generally low, but one study was at high risk of selection bias due to their use of the block method of randomisation; one study did not adequately report randomisation methods; and two studies may not have included a sufficient number of participants to adequately answer the questions posed by the studies. We found that from the data currently available there appears to be no difference in death within 30 days of the procedure between endovascular repair and open repair. Endoleaks were reported in 44 participants from three studies. The data on complications (myocardial infarction, stroke, combined cardiac complications, renal complications, spinal cord ischaemia, reoperation, amputation, and respiratory failure) are not robust enough at this point to make any strong conclusions on superiority of either repair technique, but emergency endovascular aneurysm repair (eEVAR) may be associated with a lower risk of bowel ischaemia. No robust conclusion can be made on outcomes at six months or one year. More studies are needed to better understand whether or not one of the aneurysm repair techniques, endovascular or open surgical, is superior based on patient outcomes. We found from the data available moderate-quality evidence suggesting there is no difference in 30-day mortality between eEVAR and open repair. Not enough information was provided for complications for us to make a well-informed conclusion, although it is possible that eEVAR is associated with a reduction in bowel ischaemia. We downgraded the quality of the evidence as some studies contained too few participants, not all studies reported on all complication outcomes, and the number of complications occurring between studies varied substantially.
We found one small randomised trial (involving 36 women) that compared prostaglandin E2 intravaginal gel administered before caesarean section compared with a placebo gel. The information obtained from this study did not permit us to be certain that prostaglandins improve neonatal breathing following planned caesarean section at term. Only one baby in the placebo group had respiratory distress assessed as rapid breathing. Further studies have to be carried out in order to find out the impact of prostaglandins on the newborn lungs after caesarean section.
We identified 26 new studies in this update, of which 9 await assessment and 17 trials (N = 3105) were added. We included a total of 28 trials involving 4195 infants with acute bronchiolitis. Nebulised hypertonic saline may reduce hospital stay by 10 hours in comparison to normal saline for infants admitted with acute bronchiolitis. We found that 'clinical severity scores', which are used by doctors to assess patient health, for children treated as outpatients or in hospital improved when administered nebulised hypertonic saline compared to normal saline. Nebulised hypertonic saline may also reduce the risk of hospitalisation by 14% among children treated as outpatients or in the emergency department. We found only minor and spontaneously resolved adverse effects from the use of nebulised hypertonic saline when given with treatment to relax airways (bronchodilators). Reductions in hospital stay were smaller than previously thought. However, an average reduction of 10 hours in the length of hospital stay for infants is significant because bronchiolitis usually has a short duration. Nebulised hypertonic saline appears to be safe and widely available at low cost. The quality of the evidence was low to moderate: there were inconsistencies in results among trials and risk of bias in some trials. Future large trials are therefore needed to confirm the benefits of nebulised hypertonic saline for children with bronchiolitis treated as outpatients and in hospital.
We included 20 studies (924 people with CF, almost equal gender split, aged six months to 59 years); 16 studies compared oral supplements to placebo ('dummy' treatment) and four compared inhaled supplements to placebo. Oral supplements We are uncertain whether NAC changes lung function (forced expiratory volume in one second (FEV1) % predicted) at three months (four studies, 125 participants, very low-quality evidence), but at six months two studies (109 participants) reported NAC probably improved FEV1 % predicted (moderate-quality evidence). One study (46 participants) reported a greater change in FEV1 % predicted with placebo than with a combined vitamin and selenium supplement after two months. One study (61 participants) reported little or no difference in quality of life (QoL) scores between NAC and control after six months (moderate-quality evidence), but the two-month combined vitamin and selenium study reported slightly better QoL scores in the control group. NAC probably made no difference to body mass index (BMI) (one study, 62 participants, moderate-quality evidence). One study (69 participants) reported that a mixed vitamin and mineral supplement may lead to a lower risk of pulmonary exacerbation at six months than a multivitamin supplement (low-quality evidence). Nine studies (366 participants) did not find any clear and consistent differences in side effects between groups (evidence ranged from low to moderate quality). Vitamin E and β-carotene studies consistently reported greater levels of these antioxidants in blood samples. Inhaled supplements In two studies (258 participants), inhaled glutathione probably improved FEV1 % predicted compared to placebo at three months but not at six months (moderate-quality evidence); these studies also reported a greater improvement in FEV1 litres with glutathione compared to placebo at both time points. Two studies (258 participants) found little or no difference in the change in QoL scores (moderate-quality evidence). One two-month study (16 participants) and a 12-month study (105 participants) reported no difference between groups in the change in BMI. There was no difference in the time to the first pulmonary exacerbation in one six-month study. Two studies (223 participants) reported no difference between groups in side effects (low-quality evidence) and another study (153 participants) reported that the number of serious side effects were similar across groups. Vitamin and mineral supplements do not seem to improve clinical outcomes. Inhaled glutathione appears to improve lung function, while oral administration lowers oxidative stress, with benefits to lung function and nutritional measures. Intensive antibiotic and other concurrent treatments for people with CF and chronic infection mean it is difficult to assess the effect of antioxidants without a very large and long study. Future research should look at how antioxidants affect people with CF taking CFTR modulator therapies. Evidence ranged from very low to moderate quality. All but one study had some bias; mostly because data were not fully reported (likely to affect our results). We were also largely unsure if participants knew which treatment they received, both in advance and once the studies started (unsure how this might affect our results).
We found eight trials with 660 participants to include in the review. Seven of the trials (623 participants) compared CCT to an alternative activity. None of the included trials examined development of dementia, so this review presents no evidence on whether taking part in computerised cognitive training will help to prevent dementia. Our main finding in relation to all of the other outcomes in which we were interested was that the overall quality of the evidence was very low. This very low quality was mainly due to small sample sizes, problems with study methods, and differences between trials. Therefore, although we found some evidence for a few benefits of CCT for cognition, we were highly uncertain about study results and consider it likely that future research might lead to different results. Unfortunately, it is not yet possible to answer our review question with any certainty. We think it remains an important area for further study. We would like to see larger studies, which would be more able to detect effects of CCT, and longer studies, which are needed to show whether there are any benefits, whether benefits are long-lasting, and whether there is a chance of preventing or delaying the development of dementia.
This review aimed to evaluate the beneficial and harmful effects of different types and modes of antibiotic therapy in the treatment of spontaneous bacterial peritonitis in cirrhotic patients. Thirteen trials were included; each one of them compared different antibiotics in their experimental and control groups. No meta-analyses could be performed, though data on the main outcomes were collected and analysed separately for each included trial. Based on the identified evidence, we cannot suggest the most appropriate management to treat spontaneous bacterial peritonitis in regard to the type, dosage, duration, or administration route of the antibiotic therapy. The clinical trials found dealt with different types of antibiotics, and, therefore, could not be combined. This review found no evidence that the effect or safety of one antibiotic is more beneficial than another. Further randomised clinical trials with an adequate design, including a large number of participants and sufficient duration should be carefully planned to provide a more precise estimate of the beneficial and harmful effects of antibiotic treatment for spontaneous bacterial peritonitis.
This Cochrane Review summarises evidence from 14 randomised controlled studies evaluating the effectiveness and safety of scopolamine for motion sickness. The results show that scopolamine is more effective than placebo and scopolamine-like derivatives in the prevention of nausea and vomiting associated with motion sickness. However, scopolamine was not shown to be superior to antihistamines and combinations of scopolamine and ephedrine. Scopolamine was less likely to cause drowsiness, blurred vision or dizziness when compared to these other agents.
We searched medical databases on 4 June 2018 for randomised trials (experimental studies where people are randomly allocated to one of two or more treatment groups) to determine whether there is any benefit to radiotherapy before surgical treatment for people with rectal cancer in terms of reducing the risk of dying from any cause, the risk of dying from cancer, and the risk of cancer recurring in the pelvis. We considered high-dose regimen of radiotherapy followed by any type of surgical treatment to remove cancer of the rectum. We found four trials involving 4663 people with operable rectal cancer. Our results suggest that administering short-course radiotherapy before surgery probably reduces mortality. However, when our analysis was limited to a contemporary type of surgery (total mesorectal excision), there was no evidence of a difference between the group receiving radiotherapy before surgery and the group receiving surgery alone. There may be little or no difference between groups in cancer-related death when short-course radiotherapy is used. We found moderate quality evidence that using preoperative radiotherapy compared to surgery alone may provide substantial benefit in terms of reduction of local recurrence of the cancer. There was little or no effect of preoperative radiotherapy on curative resection and sphincter-sparing surgery. We found higher rates of sepsis, surgical complications, and sexual complications in participants treated with radiotherapy compared to those who received only surgery. Overall the studies were well-designed. We judged the quality of the evidence as moderate for cancer recurrence and overall mortality, as there were serious concerns regarding the applicability of the findings to the contemporary management of rectal cancer. We further downgraded the quality of the evidence for the remaining outcomes due to imprecise results and/or variations between the trials regarding the criteria used to define rectal cancer, the stage of participants, preoperative imaging used for assessing stage, the type of surgery performed, the radiation dose and fractioning, the time between radiotherapy and surgery, and the use of adjuvant or postoperative therapy.
The review authors searched the medical literature to identify relevant studies that compared the effect of vitamin A supplementation versus control on death, illnesses, and side effects in randomly selected infants aged one to six months. The literature is current to 5 March 2016. The search identified 12 studies that involved 24,846 infants. Most of the studies were well conducted and included children from Asia, Africa, and Latin America. The results of the studies provided no convincing evidence that vitamin A supplementation reduces death or illness in infants one to six months of age (quality of evidence: moderate). Supplementation had no beneficial effects to reduce death or illness due to diarrhoea or pneumonia. Similarly, vitamin A supplementation did not reduce the proportion of children with vitamin A deficiency based on their blood levels of vitamin A (quality of evidence: moderate). Infants who were given vitamin A had an increased risk of development of bulging of soft spot at the top of the head (called bulging fontanelle) and quality of evidence for this side effect was high. However, this adverse effect did not increase subsequent risk of death or fits. In summary, vitamin A supplementation in infants one to six months of age did not reduce death or illness; however, it increased the risk of bulging fontanelle.
We included eight studies involving people with neutropenia and fever and comparing short antibiotic therapy to long antibiotic therapy until normalisation of neutrophils. A total of 662 episodes of fever in people with neutropenia were randomly assigned to a treatment group (314 to short antibiotic treatment and 348 to long antibiotic treatment). All trials excluded people who had bacteria growing in any culture before the time of randomisation. All studies except two excluded people with infection in a specific organ. Three trials did not report funding sources; three were funded by academic sponsors; one had academic sponsorship, but the antibiotics and placebos were provided by pharmaceutical companies; and one was sponsored by government funding. There was no difference in mortality between the short- and long-antibiotic therapy arm. There was no difference in the number of people with severe infections presenting as bacteria in blood. There were more cases of infections with positive cultures in people treated with short antibiotic courses compared to long antibiotic courses, but there was no difference in the rate of unfavourable outcome such as recurrence of fever, need for rehospitalization, and change or restart of antibiotics. We found no differences in the rate of fungal infections and development of antibiotic resistance, with few studies reporting the latter outcome. The number of days with fever was lower for people treated with short antibiotic courses compared to those treated with long antibiotic courses. In all trials the number of antibiotic treatment days was fewer in the short-antibiotic therapy arm by three to seven days compared to the long-antibiotic therapy arm. Data on hospital length of stay were insufficient to permit any meaningful conclusions. The overall certainty of evidence was low or very low, permitting little confidence in the results presented. Most of the included studies were old and not adequately designed. There were also many differences between the studies in terms of design and inclusion criteria. We assessed the certainty of the evidence for the primary outcome of all-cause mortality as low and for the outcomes of clinical failure and bacteraemia occurring after randomisation as very low.
There is insufficient evidence to establish the value of combination therapy over monotherapy for people with IA. We included 23 studies in this review, all at high risk of bias (i.e. high chance of giving invalid results). Twenty-two of the trials were in patients with RA and one in a mixed population (RA and osteoarthritis). There were no studies in patients with AS, PsA or SpA. Included studies were old (all but one were published before 1990) and patients were, in general, not on optimal disease-modifying antirheumatic drugs, as is standard current practice. Therefore, it is not possible to draw conclusions about the value of combination pain therapy over monotherapy for people with IA. Importantly, there are no studies addressing the value of combination therapy for patients with IA who have persistent pain despite optimal disease suppression. Well designed studies are needed to address this question.
This represents the first update of this review, which was published in 2012 (Adams 2012). Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is an HMG-CoA reductase inhibitor that is prescribed to prevent adverse cardiovascular events and to lower blood total cholesterol and LDL-cholesterol. It is therefore important to know the magnitude of the effect that atorvastatin has on cholesterol. We searched for all evidence obtained from three- to 12-week trials reporting the effect of atorvastatin on blood cholesterol. This update found 42 additional trials and reports on 296 trials in 38,817 participants. Atorvastatin showed a consistent effect in lowering blood cholesterol over the dose range of 2.5 to 80 mg daily. The effect was greater with higher doses than with lower doses. Atorvastatin works similarly to rosuvastatin in lowering cholesterol but is about three-fold less potent. Risk of bias for all assessed trials was high. Review authors were unable to assess harms of atorvastatin because the included trials were too short, and because only 34 included trials assessed harms.
Five trials, including 1476 participants, were included in the review. Three of the five trials were stopped early. The risk of bias of most of the trials was high or unclear due to incomplete reporting of methods and results. Most of the trials were not large enough to detect any true effect of the intervention. Trials either did not report the results of important outcomes or the results of important outcomes were not uniform between the trials. The evidence from the three trials suggested that the addition of interferon to first-line chemotherapy did not alter the overall survival in post-surgical women with advanced EOC compared with chemotherapy alone. On the contrary, there is evidence that interferon in combination with chemotherapy worsened progression free survival in post-surgical women with advanced EOC compared with chemotherapy alone. Furthermore, there is not enough evidence that interferon therapy alone improves overall survival or progression free survival in post-surgical women who have undergone first-line chemotherapy when compared with observation alone.
This review explores whether the blood pressure lowering effect of dihydropyridine calcium channel blockers in adults (aged 18 years or over) with high blood pressure (systolic blood pressure (the upper blood pressure reading) of at least 140 mmHg or diastolic blood pressure (the lower blood pressure reading) of at least 90 mmHg, or both of these) is consistent or variable over a 24-hour period. We performed a review of studies that compared the 24-hour blood pressure lowering effects of six of these drugs versus a control treatment for at least three weeks. Blood pressure needed to be measured by an ambulatory blood pressure monitor, which is a device that automatically measures blood pressure at regular intervals. We performed searches for clinical trials up to February 2014. We found 16 trials involving 2768 participants that studied five drugs given once a day (amlodipine, lercanidipine, mandipine, nifedipine, and felodipine) and one drug given twice a day (nicardipine). The amount of blood pressure lowering by dihydropyridine calcium channel blockers stayed relatively the same at every hour throughout a 24-hour day. The average hourly differences in blood pressure were between 9.45 mmHg and 13.2 mmHg for systolic blood pressure and between 5.85 mmHg and 8.5 mmHg for diastolic blood pressure. At the present time, the benefits and harms of this pattern of blood pressure lowering are unknown. We judged the overall quality of the evidence to be moderate. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
We searched the Cochrane Schizophrenia Group Trial's Register in January 2015 and March 2016 and found four relevant studies involving 300 adults diagnosed with both SMI and PTSD. The participants received treatments that included trauma-focused cognitive behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing (EMDR), and brief psychoeducation. All of these therapies support individuals to work through and process the memories, emotions and behaviours associated with trauma. Key results When TF-CBT was compared to the care usually received, no effect for reducing PTSD, psychotic, depressive or anxiety symptoms or improving quality of life, was noted. There was some low-quality evidence from two studies that people with SMI and PTSD receiving TF-CBT were more likely to recover from PTSD, that is, having PTSD symptoms which are below diagnostic threshold. TF-CBT was not linked to an increase in side effects. A comparison of people receiving EMDR against those awaiting treatment showed a favourable effect for reducing the symptoms of PTSD (very low-quality evidence). Again, there was no difference in side effects. No data were available for the effect of EMDR on quality of life, psychosis, depression or anxiety. A comparison of TF-CBT with EMDR indicated no difference in reduction of PTSD symptom severity (very low-quality evidence). Finally, when TF-CBT was compared with brief psychoeducation there was no evidence that either therapy was superior in treating a range of PTSD symptoms. Quality of the evidence The review identifies limited, low-quality evidence on TF-CBT and EMDR. The effects of these treatments in reducing the symptoms of PTSD remain unclear although they do not appear to cause any more side effects than waiting for treatment. However, many important outcomes of interest have not been reported on and more research into the benefits of trauma-focused psychological interventions for individuals with SMI and PTSD is required.
The review includes 26 studies, found through electronic searching of relevant databases, with a total of 2184 participants. All trials examined the effectiveness of valproate as an add on to antipsychotics. With the exception of two studies, the studies were small, and most of them were short-term and poorly reported. Data from the included trials showed that participants receiving valproate plus an antipsychotic had better clinical response, compared to those taking an antipsychotic with a placebo. However, this advantage was lost when lower-quality trials were taken out of the analysis. Valproate was also indicated to be effective in controlling excitement and aggression. Acceptability and overall tolerability of the combined treatment was similar between treatment groups and did not cause more weight gain, however, adding valproate did cause greater sedation and dizziness. No trial reported effect on quality of life. Evidence is limited and firm conclusions cannot be made. For the main outcomes of interest, the review authors judged the quality of evidence to be low or very low quality, due to methodological issues in the reviewed studies. Most of them were small, short-term and did not blind the participants or personnel. Large, double-blind and long-term randomised trials should be undertaken to properly determine the clinical effects of adding valproate to antipsychotic treatment for people with schizophrenia. This summary was written by Ben Gray, Senior Peer Researcher, McPin Foundation. mcpin.org/
We searched until March 2017 for evidence on use of pulse oximetry to detect CCHD in newborn infants and found 21 studies. These studies used different thresholds to define a pulse oximetry test as positive. We combined all studies using a threshold around 95% (19 studies with 436,758 newborn infants). This review found that for every 10,000 apparently healthy newborn infants screened, around six of them will have CCHD. The pulse oximetry test will correctly identify five of these newborn infants with CCHD (but will miss one case). Newborn infants who are missed could die or experience major morbidity. For every 10,000 apparently healthy newborn infants screened, 9994 will not have CCHD. The pulse oximetry test will correctly identify 9980 of them (but 14 newborn infants will be investigated for suspected CCHD). Some of these infants may be exposed to unnecessary additional tests and a prolonged hospital stay, but a proportion will have a potentially serious non-cardiac illness. The number of newborn infants incorrectly investigated for CCHD decreases when pulse oximetry is performed longer than 24 hours after birth. We judged the included studies to be mainly at low or unclear risk of bias for several of the certainty domains assessed. Some studies used less robust methods to verify negative results. We considered the overall certainty of the evidence as moderate.
This review identified one study involving 200 pregnant women who received nitrofurantoin (antibiotics) and close surveillance (regular clinic visit, urine cultures and antibiotics when a positive culture was found) or close surveillance alone. Suppressive therapy with daily dose of nitrofurantoin and close surveillance was not shown to prevent RUTI compared with close surveillance alone but the evidence was of very low quality. A significant reduction of asymptomatic bacteriuria (presence of bacteria in the urine without the symptoms of a UTI) was found in women with a high clinic attendance rate who received nitrofurantoin and close surveillance. Due to lack of evidence no conclusions can be drawn. Future randomised controlled trials comparing different pharmacological and non-pharmacological interventions are necessary to assess the optimal intervention to prevent RUTI in women who are pregnant. Such trials should report on a comprehensive range of outcomes for both women and infants.
The review authors identified only one controlled trial, from New Zealand. This trial randomised 167 women who were between 24 and 36 weeks' pregnant where ultrasound showed a small-for-gestational-age baby. They received a set combination of tests either twice-weekly or fortnightly. With more frequent testing, women were 25% more likely to have induced labour. Overall their babies were born four days earlier than in the fortnightly surveillance group where spontaneous onset of labour was more likely to occur. The mean gestational age at birth was just under 38 weeks in the twice-weekly group and just over 38 weeks in the fortnightly group, which was unlikely to have an impact on the health of the newborn. The number of caesarean sections, either for fetal distress or because of failure of induction, was no different. No information was available on length of antenatal hospital admission or operative vaginal births and infants were not followed up to determine neurodevelopment and cerebral palsy. This study excluded pregnancies with abnormal Doppler studies and disorders of the amniotic fluid. More studies are needed and the women’s views on the testing are also important.
We searched the medical literature for randomised controlled trials (where people are allocated at random to one of two or more treatment groups) that compared heated and cold CO2. We analysed data from the trials for changes in core temperature. We also compared post-operative pain scores and pain medication requirements, length of hospital stay, length of surgery and fogging of the surgical video camera lens. Evidence is current to September 2016. We identified and included 22 trials. There was an increase of 0.31 °C in the heated, humidified CO2 group compared to the cold CO2 group but the data were heterogeneous (highly variable). However, if the analysis was limited to the eight low-risk-of-bias studies that reported core temperatures, no significant difference was found. Also, there was no temperature difference for heated and non-humidified gas compared to cold gas. There was no difference in postoperative pain with heated or cold insufflation. However, pain medication use was higher in only the heated, non-humidified group on postoperative days one and two. Heated gas apparently did not change length of hospitalisation, lens fogging or length of operation. Recovery room stay was shorter with heated gas but the data was heterogeneous (highly variable). When we only included studies at low risk of bias, the data became homogeneous (less variable) and the recovery room time was not significantly different between the heated and cold gas groups. While heated, humidified gas leads to slightly smaller decreases in core body temperatures, this does not account for improvement in any patient outcomes. Therefore, there is no clear evidence for the use of heated gas insufflation, with or without humidification, in laparoscopic abdominal surgery.
Five small studies, each with 24 to 54 participants, included 177 participants in total with painful diabetic neuropathy or postherpetic neuralgia. Studies were randomised and double-blind, but all had one or more sources of potential major bias that could lead to overestimation of efficacy. It was not possible to combine information from the different studies, but individually they indicated some benefit from desipramine (usually at a dose between 100 mg and 150 mg daily), compared with placebo, at the expense of increased adverse events. There was not enough information about other comparators to draw any conclusions. There was too little information, which was of inadequate quality, to be sure that desipramine works as a pain medicine in painful diabetic neuropathy or postherpetic neuralgia, and no information about other types of neuropathic pain. Other medicines have been shown to be effective as treatments of first choice.
Twenty-three studies fulfilled our inclusion criteria with a total of 3872 and 2915 participants in the intervention and in the control group, respectively. The methodological quality of all the studies was rated intermediate to low. Trials duration was no longer than one year. The level of glycosylated haemoglobin, a marker of diabetes control, was lower in the long acting insulin group, but the observed difference was of doubtful clinical significance. Longer acting insulins were superior mostly in their nocturnal effect, which resulted in a lower level of fasting glucose levels and fewer episodes of nocturnal hypoglycaemia. No data on long term complications were available.  The currently available data can not substantiate conclusions on the benefits and risks of long acting insulins, and long-term data are of need.
This review found evidence suggesting that arterial infusion is more effective than intravenous infusion. The risk of haemorrhage with intravenous infusion is high. However, none of the different arterial infusion techniques studied have been shown to be more effective in preventing limb loss, amputation or death. More research is needed to confirm these findings.
We searched the medical literature for clinical trials up to 19 March 2019. We found 59 randomised trials that compared BTURP with MTURP. These studies included a total of 8924 patients. The longest period of follow-up for the outcomes of interest was 12 months after treatment. Compared to MTURP, BTURP probably results in similar reduction in urinary symptoms and bother. It probably slightly reduces both the risk of TUR syndrome and the need for blood transfusion. Erectile function is probably similar after both procedures, as is the risk of urinary incontinence and the need for a repeat procedure. The quality of evidence for the outcomes of ability to pass urine, patient bother, TUR syndrome, need for blood transfusion, and erectile function was considered to be moderate. The quality of evidence for the outcomes of urinary leakage after the procedure and need for a repeat procedure was low.
Therefore, trials have been performed with agents that prevent clotting of blood platelets (antiplatelet agents). In this review of seven trials, including 1385 patients, that studied the effects of antiplatelet agents on the outcome after SAH, we found that patients who were treated with antiplatelet agents had a poor outcome less often, and secondary ischaemia less often than patients that received no antiplatelet agent, but the results were not statistically significant and so no definite conclusion can be drawn. Moreover, patients who are treated with antiplatelet agents might have a slightly higher risk of bleeding. Based on these results we conclude that antiplatelet agents after SAH cannot be recommended at the present time.
The objective of this systematic review was to identify the effectiveness of lycopene in the prevention of prostate cancer. This review identified 3 relevant studies, comprising 154 participants in total. Two of the studies were assessed to be of 'high' risk of bias. Meta-analysis of two studies indicated no statistical difference in prostate specific antigen (PSA) levels between men randomised to receive lycopene and the comparison group (MD -0.34, 95% CI -2.01 to 1.32). None of the studies assessed prostate cancer mortality. No other meta-analyses were possible since other outcomes assessed only had one study contributing data.
We included 138 randomised clinical trials. All included trials were at high risk of bias. The 138 trials used 51 different DAAs. Of these, 84 trials assessed DAAs on the market or under development; 57 trials were on DAAs withdrawn from development or the market. Trials were conducted from 2004 to 2016. The trials were from all over the world including 34 different countries. We included 17 trials where all the participants had previously been treated for hepatitis C (treatment-experienced) before being included in the trial. There were 95 trials that included only participants who had not been previously treated for hepatitis C (treatment-naive). The intervention periods ranged from one day to 48 weeks with an average of 14 weeks. The combined intervention period and follow-up period ranged from one day to 120 weeks with an average of 34 weeks. We could not reliably determine the effect of DAAs on hepatitis C-related morbidity or death from any cause. There were no data on hepatitis C-related morbidity and very few deaths occurred over the course of the trials (15 deaths/2377 direct-acting antiviral participants (0.63%) versus 1 death/617 control participants (0.16%), very low quality evidence). Based on very low quality evidence, 5.2% people treated with DAAs had one or more serious adverse events versus 5.6% participants who were untreated during the observation period. When analysed separately, simeprevir was the only direct-acting antiviral that showed evidence of a beneficial effect when assessing risk of a serious adverse event. Our analyses, however, showed that the validity of this result is questionable and that 'play of chance' might be the cause for the difference. There was not enough information to determine if there was any effect of DAAs on other clinically relevant outcomes. Our results confirm that DAAs seem to reduce the number of people who have the hepatitis C virus in their blood from 54.1% in untreated people to 23.8% in those who were treated. Because the loss of detectable hepatitis C virus in the blood stream is only a blood test, the studies could not tell what this result means in the long term. Due to several limitations (e.g. lack of blinding, lack of relevant data, missing data, no published protocol) we assessed the quality of the evidence in this review as very low or low quality. First, all trials and outcome results were at high risk of bias, which means that our results presumably overestimate the beneficial effects of DAAs and underestimate any potential harmful effects. Second, there were limited data on most of our clinical outcomes, that is, there were only relevant clinical data for meta-analyses on all-cause mortality and serious adverse events, and for these, data were sparse. There are no long-term trials that have assessed whether or not DAA treatment improves morbidity or mortality.
Researchers from Cochrane searched for all available literature up to 30 November 2014. One randomised controlled trial met our inclusion criteria. In this review, the efficacy of oral zinc salt was compared with placebo. One study enrolling 294 infants was identified. This study evaluated oral zinc salt, given in a dose of 5 mg twice daily to infants between 25 and 168 hours old. The administration of oral zinc salt did not affect the incidence of jaundice (hyperbilirubinaemia) in these infants.
The aim of this review was to find out whether statins prevent death and complications from heart disease in people who have had a kidney transplant. We included 17 studies in 3282 adults with a functioning kidney transplant which compared statin therapy to a placebo or standard treatment. Based largely on information from a single, large and well-conducted study, statins may reduce complications from heart disease although information from the available research is imprecise. The effects of statin treatment on death overall, stroke, kidney function and side-effects are uncertain in people with a kidney transplant. Large additional studies of statin therapy may improve our confidence that statin treatment can safely prevent serious complications from heart disease for people who have a kidney transplant.
This review includes trials involving 2804 children up to eight years old, undergoing general anaesthesia. The trials assessed two types of cuffed tubes: conventional and Microcuff™ tubes (the latter consisting of a different type of balloon with low pressure levels that is more suitable for children's windpipes). The primary outcome was postextubation stridor. This is a potentially serious problem resulting from the narrowing of the airway and can be identified by a high-pitched noise following removal of the tube. Other factors assessed were the need to exchange the tube for another; to put the tube back in; to use drugs such as epinephrine (adrenaline) or corticosteroid (an anti-inflammatory); and to admit a child to an intensive care unit to treat stridor; the cost of medical gas per child; and the ability to deliver appropriate volumes of oxygen. Two trials (involving 2734 children) measured postextubation stridor and found no difference between the groups. The need to exchange tubes for others was 93% lower in the cuffed ETT group. One trial involving 70 children showed that cuffed tubes reduced the amount of anaesthetic gases required, and consequently the cost involved. The quality of evidence was low to very low, as there were problems with the study designs. Comparisons between cuffed and uncuffed tubes need to be interpreted with caution. Further studies are needed to evaluate the benefits and risks of the two types of tubes. Several gaps remain in the information available around this question. Large, well-conducted clinical trials should clarify factors such as the ability of these tubes to provide adequate amounts of oxygen, and the respiratory complications that occur with the wide use of cuffed tubes in children.
There are no nicotine vaccines currently licensed for public use, but there are a number in development. We found four trials (2642 participants) comparing nicotine vaccines to a placebo. These did not show that vaccines help people to stop smoking in the long term. All four trials were conducted by pharmaceutical companies as part of the drug development process and involved vaccines administered by injection. There were no trials testing whether nicotine vaccines helped keep people who had stopped smoking from starting to smoke again. Only two of the four trials had full results available. The two trials showed nicotine vaccines to be generally safe, with most side effects being mild or moderate. In one trial, flu-like symptoms were found to be a side effect of the nicotine vaccine. If nicotine vaccines become available to the general public they may have changed from the ones tested in these studies, meaning the results reported in this review, including those on side effects, may not apply to all nicotine vaccines.
This review examined data from 9 trials including a total of 3327 participants. Study participants were assigned using a random method to take pregabalin, placebo, or another antiepileptic drug in addition to their usual antiepileptic drugs. Participants taking pregabalin were more than twice as likely to have their seizure frequency reduced by 50% or more during a 12-week treatment period compared to those taking placebo, and were nearly four times more likely to be completely free of seizures. Pregabalin was shown to be effective across a range of doses (150 mg to 600 mg), with increasing effectiveness at higher doses. There was also an increased likelihood of treatment withdrawal with pregabalin. Side effects associated with pregabalin included ataxia, dizziness, fatigue, somnolence, and weight gain. When pregabalin was compared to three other antiepileptic drugs (lamotrigine, levetiracetam, and gabapentin), participants taking pregabalin were more likely to achieve a 50% reduction in seizure frequency than those taking lamotrigine. We found no significant differences between pregabalin and levetiracetam or gabapentin as add-on drugs. We rated all included studies as at low or unclear in risk of bias due to missing information about the methods used to conduct the trial and a suspicion of publication bias. Publication bias can occur when studies that report non-significant findings are not published. We suspected publication bias because the majority of included studies showed significant findings and were sponsored by the same drug company. We assessed the certainty of the evidence for the primary outcome of reduction in seizure frequency as low, meaning that we cannot be certain that the finding reported is accurate. However, we rated the certainty of the evidence for the outcomes seizure freedom and treatment withdrawal as moderate, so we can be fairly confident that these results are accurate. There were no data regarding the longer-term effectiveness of pregabalin, which should be investigated in future studies. The evidence is current to 5 July 2018.
This review of trials found that UFH and LMWH when given to patients with high-risk unstable angina or NSTEMI in the acute phase of treatment, in addition to standard therapy with aspirin, prevent more heart attacks than placebo but do not reduce mortality, the need for revascularization procedures or recurrent angina. Although there was limited reporting of side-effects, heparins caused more cases of minor bleeding.
We included 38 studies that involved 7924 young people (aged 5 to 16 years) among whom a variety of dental sealants was used to prevent tooth decay. Young people in the studies represented the general population. The review includes studies available from a search of the literature up to 3 August 2016. We assessed all studies as being at high risk of bias because the dental professionals who are measuring the outcomes can see whether or not sealant has been used. Fifteen studies compared resin-based sealants to no sealants and found that children who had sealant applied to their back teeth were less likely to have tooth decay in their back teeth than children with no sealant. We were able to combine data from seven of these studies (including two published since 2010), which involved children who were aged from 5 to 10 years when the sealants were applied. This showed that if 40% of back teeth develop decay over 24 months, using sealant reduces this to 6%. Similar benefits for resin-based sealants were shown up to four years. The effect appeared to persist when measured up to nine years, but there was less evidence. Results were inconclusive when glass ionomer-based sealant was compared with no sealant and when one type of sealant material was compared with another. Four studies assessed possible problems from using sealants; none were reported. We found moderate-quality evidence that resin-based sealant is more effective than no sealant for preventing tooth decay, reducing it by between 11% and 51% more than in children without sealant (measured two years after application). 'Moderate quality' means we are reasonably certain of this finding, although it is possible that future research could change it. Most of the studies included in this analysis were carried out in the 1970s. We are not able to draw conclusions about the other comparisons included in our review as the available evidence is very low quality. More studies with long follow-up times are needed.
We chose to focus on Pycnogenol® as this supplement is a standardised product, many trials have been conducted, and it is extensively marketed internationally. Our review aimed to assess the efficacy and safety of Pycnogenol® as a treatment for chronic disorders. We identified 15 eligible randomised controlled trials with a total of 791 participants which addressed seven different chronic conditions: asthma (two studies); attention deficit hyperactivity disorder (one study), chronic venous insufficiency (two studies), diabetes (four studies), erectile dysfunction (one study), hypertension (two studies) and osteoarthritis (three studies). Due to small sample size, limited number of trials per condition, variation in outcomes evaluated and outcome measures used, as well as the risk of bias in the included studies, no definite conclusions regarding the efficacy and safety of Pycnogenol® are possible.
Data from some experimental and human studies have suggested that edaravone, a neuroprotective agent, may be beneficial for people with acute ischaemic stroke. It has been widely used in China to treat stroke. To obtain a reliable assessment of the effects of edaravone in acute ischaemic stroke, we reviewed data from three studies involving 496 participants. The quality of the trials was moderate. It would appear that edaravone is an effective treatment for acute ischaemic stroke. However, more high-quality and bigger sample trials are needed to confirm this result.
This review included four trials, involving a total of 292 participants. All four trials had flawed methods that could affect the reliability of their findings. No data could be pooled for long-term measures of function or pain. The largest trial found no evidence of differences between surgery and conservative treatment in patient-reported symptoms or walking difficulties at seven years follow-up. The second trial found better results for the surgical group for function but not pain at 27 months, while the third trial reported no difference between the two groups in clinical outcome at 3.5 years. In all four trials, there were some patients in the conservative treatment group who were treated surgically because the repositioning of the fractured bone was judged unsuccessful. Otherwise, there were no significant differences between the two groups in any of the reported complications nor in radiological signs of osteoarthritis. Overall, there was not enough reliable evidence to draw conclusions about whether surgery or conservative treatment is more appropriate for treating broken ankles in adults.
We conducted a literature search on 29 May 2018 for studies that compared DBS with sham stimulation (same surgical procedure, but no electrical impulses are delivered through the electrodes placed in the brain), best medical therapy, and placebo (a pretend medicine). We found two studies that compared DBS with sham stimulation, and included a total of 102 participants. One study included participants with dystonia of the limbs and trunk, and the other with dystonia of the neck. Participants received active DBS for a total of six months. The average age of people in the studies was 50 years; the average duration of the disease was 16 years. Both studies were funded by a DBS device manufacturer with possible interests in the results of the studies. For limb and trunk dystonia, DBS may improve symptoms, self-assessed clinical status, and functioning. The results showed that for neck dystonia, DBS may improve symptoms, clinical status, functioning, and mood. For either type of dystonia, we are uncertain about the impact that DBS has on harmful or undesired events, or treatment tolerability. The overall quality of the evidence for neck, limb, and trunk dystonia was low to very low. Further research is needed to draw conclusions about the clinical efficacy, safety, and tolerability of DBS in people with dystonia, especially beyond the three- to six-month duration of the included studies.
We searched for and included any randomised controlled trials published up to October 2019. We found two small randomised controlled trials, with a low risk of bias, comparing tonsillectomy or adenotonsillectomy against non-surgical interventions (total of 67 participants, with data from 65 analysed). One study (39 participants) used the adenotonsillectomy procedure in the intervention group and followed up patients for 18 months. This study applied stringent criteria for diagnosing PFAPA when recruiting patients. The other trial (28 participants) only removed the tonsils and followed up patients for up to six months. Less stringent recruitment criteria were applied and it was possible that patients with other types of recurrent sore throats might have been recruited and included in the trial. Neither study masked participants and investigators to the type of treatment received. Participants in the control groups of both studies received standard medical treatment. The two trials showed that children with PFAPA are likely to benefit from tonsillectomy. The results showed that children who had surgery were about four times more likely to be free of PFAPA symptoms from the point of surgery until the end of the follow-up periods for these studies. There was an overall decrease in the number or frequency of PFAPA episodes experienced by the children in the surgery group. While the average child in the control arm had an average of one episode every two months, this was reduced to less than one-tenth of that; i.e. about one episode every two years among children who had surgery. In addition, the length of each episode was also shortened by an average of 1.8 days (reduced from an average of 3.5 days to 1.7 days per episode) for children who had surgery. Courses of corticosteroids can be used to treat episodes of symptoms in children with PFAPA. One trial reported that the proportion of children given a course of corticosteroids was lower in children who received surgery. The trials reported no complications of surgery. However, these studies might be too small to detect important but rarer types of complications such as bleeding from the surgery. Other outcomes such as absence from school or quality of life were not reported. The certainty of the evidence is moderate (that is, further research is likely to have an important impact on our confidence in the estimates of effects and may change these estimates). The studies are very small. Studies with larger numbers of patients are required to estimate the effects more precisely. There is also some uncertainly about whether the effects observed in these studies can be replicated in most children with PFAPA for two reasons. It is unclear whether some children who did not have PFAPA had been included in the study that applied less stringent inclusion criteria for PFAPA diagnosis. Secondly, it is uncertain whether the treatment received in the control arms of the studies was adequate and represented current practice.
We searched the medical literature (January 2017) and identified seven studies that met the inclusion criteria; one study was ongoing and six studies were eligible for inclusion in the updated review. The six included studies comprised a total of 435 participants with primary spontaneous pneumothorax; 208 of these underwent simple aspiration and 227 underwent intercostal tube drainage. Study results show that tube drainage produced a better rate of immediate treatment success when compared with simple aspiration for primary spontaneous pneumothorax. However, simple aspiration was associated with shorter duration of hospitalization and may have led to fewer adverse events. Researchers noted no significant differences between the two treatments with regard to hospitalization rate, early failure rate, one-year success rate, or patient satisfaction. However, the quality of evidence presented in this review ranged between very low and moderate, making it difficult for review authors to come to definitive conclusions. Results of this review indicate that tube drainage has a better immediate success rate than simple aspiration for treating people with primary spontaneous pneumothorax. However, simple aspiration results in a shorter hospital stay and, although the evidence presented for this outcome is of low quality, may lead to fewer adverse events than are reported with tube drainage. The overall quality of evidence ranges from very low to moderate, and future research is needed to strengthen the evidence presented in this review.
We performed the present systematic review to determine the beneficial and harmful effects of dopamine agents for patients with hepatic encephalopathy. Our analyses included five small trials published in 1982 or earlier. All trials but one had high risks of bias (i.e., risks of systematic errors or risks of overestimation of beneficial effects or risks of underestimation of harmful effects). Only 144 patients were included in the five trials, and accordingly risks of random errors (i.e., play of chance) are present. Our analyses showed no significant differences regarding symptoms of hepatic encephalopathy or mortality in patients treated with dopamine agents compared with patients who received an inactive placebo or no intervention. The number of patients with adverse events seemed comparable in the two intervention groups. Based on the available evidence, we conclude that no evidence can be found to recommend or refute the use of dopamine agents for hepatic encephalopathy. More randomised placebo-controlled clinical trials without risks of systematic errors and risks of random errors seem necessary to obtain firm evidence on dopamine agents for patients with hepatic encephalopathy.
In this review we included 14 studies, randomising 1390 participants to either a pre-emptive correction of an access stenosis (i.e. before the access became dysfunctional) or a deferred correction of an access stenosis (i.e. if and when the access became dysfunctional). This review shows that pre-emptive correction of an arteriovenous access stenosis does not improve longevity of the access overall. In people using grafts pre-emptive correction does not reduce the risk of thrombosis or access loss. In people using fistulas pre-emptive stenosis correction reduces the risk of thrombosis and may prolong the longevity of the access. However, this surveillance and pre-emptive correction strategy may increase the number of access-related procedures and procedure-related adverse events. This systematic review presents, to clinicians and patients, evidence-based data that do not support the use of access surveillance and pre-emptive correction of stenosis in grafts. Although surveillance and pre-emptive correction of stenosis reduce the risk of thrombosis and may reduce the risk of access loss in fistulas, they may also increase the risk of procedure-related adverse events and health-care cost. Large multicentre clinical trials are necessary in this patient population to better clarify potential harms and expected benefits of routine surveillance and pre-emptive correction of fistula stenosis.
In this systematic review of seven randomised clinical trials including 556 patients, various methods of parenchymal transection techniques were compared. The infective complications and transection blood loss were greater in the radio frequency dissecting sealer (RFDS ) than clamp-crush technique. There were no significant differences in the mortality or in the morbidity between the other techniques of parenchymal transection. There was also no difference in the markers of liver parenchymal injury or liver dysfunction between the different methods used. Intensive therapy unit stay and hospital stay were similar. The blood transfusion requirements were lower in the clamp-crush technique than CUSA (cavitron ultrasonic surgical aspirator) and hydrojet. There was no difference in the transfusion requirements of clamp-crush technique and sharp dissection. Clamp-crush technique is quicker than CUSA, hydrojet, and RFDS. The transection speed of sharp dissection and clamp-crush technique was not compared. There was no clinically or statistically significant difference in the operating time between sharp dissection and clamp-crush techniques. Clamp-crush technique is two to six times cheaper than the other methods depending upon the number of surgeries performed each year. Clamp-crush technique is advocated as the method of choice in liver parenchymal transection because it avoids the need for special equipment and the newer methods do not seem to offer any benefit in decreasing the morbidity or transfusion requirement.
This review aimed to investigate the effects of fluphenazine (decanoate and enanthate) for schizophrenia. Searches for relevant randomised controlled trials was run in February 2011 and October 16, 2013. Authors could include and extract data from 73 studies with a total of 4870 participants. There were more studies on fluphenazine decanoate than enanthate.The review authors rated the quality of the evidence in the included trials to be low or very low. A long-term result from only one trial indicated fluphenazine decanoate reduces the rate of relapse when compared with placebo (‘dummy treatment’). Three studies found that fluphenazine decanoate produced fewer general movement disorders than oral antipsychotics. However, other results showed, overall, the effects and outcomes, including adverse effects for fluphenazine (decanoate and enanthate) are similar to other oral and depot antipsychotics. Important outcomes and information about use of services, going into hospital, satisfaction with care and costs were not reported in any study. Depot injections may offer an advantage over tablets (oral medication) in terms of people taking their medication (complying and adhering to treatment). However, this needs to be balanced with the likelihood of serious side effects, such as involuntary shaking, muscle stiffness, the inability to sit still and lowering in people’s mood. Results did not show any strong evidence that depot fluphenazine produced more adverse effects than other antipsychotics. This should be addressed in future large scale and high quality studies. This plain language summary has been written by a consumer Ben Gray from Rethink Mental Illness.
We searched several electronic databases to 5 January 2016, as well as doing some searching by hand. We included five studies in the review, which had 190 participants in total. We did not find any new studies between the previous Cochrane review in 2012 and our updated search in January 2016. Three included studies related to dental treatment (fillings and tooth extractions) and two related to orthodontic treatment (braces). Three of the five included studies compared paracetamol to a placebo (sugar tablet) and four of them compared ibuprofen to a placebo. From the available evidence, we could not determine whether or not painkillers before treatment are of benefit for children and adolescents having dental procedures under local anaesthetic. There is probably a benefit in giving painkillers before braces are fitted. Only one study reported an adverse event (one participant in each group had a lip or cheek biting injury). More research is needed. None of the included studies were at low risk of bias. The quality of the evidence is low.
We found that only one study that involved nine patients had compared home haemodialysis with in-centre haemodialysis. There was insufficient information to understand the effects of home haemodialysis on survival or need for hospital admission in this study. Home haemodialysis may improve blood pressure and physical symptoms, but may increase the burden of care for families and patients. Given the potential benefits of home haemodialysis in non-randomised studies, larger randomised trials of home haemodialysis could help inform clinical care and policy.
Ten studies included altogether 741 children and lasted between six months and 6.2 years. Results showed that individuals treated with growth hormone remain relatively short when compared with peers of normal stature. Girls treated with growth hormone were 7.5 cm taller than untreated controls (growth hormone treated group 155.3 cm and control group 147.8 cm); another trial found that children treated with growth hormone were 3.7 cm taller than children in a placebo-treated group. No serious adverse effects were reported in the included studies. Although serious adverse effects (there has been concern that growth hormone would induce new tumours or increase the likelihood of tumour relapse) may be rare, their possibility must also be taken into consideration.
We found 12 studies involving 27,482 participants that compared groups of lone parents in WtW interventions with lone parents who continued to receive welfare benefits in the normal way. All of the studies were at high risk of bias because the staff who collected the data knew when respondents were in the intervention group. In some studies, lone parents who were not in the intervention group were affected by similar changes to welfare policy that applied to all lone parents. We used statistical techniques to combine the results of different studies.These analyses suggest that WtW does not have important effects on health. Employment and income were slightly higher 18 to 48 months after the start of the intervention, but there was little difference 49 to 72 months after the studies began. In a number of studies, lone parents who were not in WtW interventions found jobs by themselves over time. It is possible that effects on health were small because there was not much change in employment or income. Even when employment and income were higher for the lone parents in WtW, most participants continued to be poor. Perhaps because of this, depression also remained very high for lone parents whether they were in WtW or not. All but one of the studies took place in the United States or Canada before the year 2000. This means it is difficult to be sure whether WtW would have the same effects in different countries at other times.
Several small trials appeared to support the practice. But the authors of this review found that other trials went unpublished once they produced unfavorable results. A controversy erupted in 1995, when a large well-designed trial with 58,050 participants did not demonstrate any beneficial effect to IV magnesium, contradicting earlier meta-analyses of the smaller trials. This review includes 26 clinical trials that had randomly assigned heart attack patients to receive either IV magnesium or an inactive substance (placebo). Their results were mixed: IV magnesium reduced the incidence of serious arrhythmias, but this treatment also increased the incidence of profound hypotension, bradycardia and flushing. However, any apparent beneficial effects of magnesium may simply reflect various biases in these trials. Additionally, there was a lack of uniformity in these trials in terms of dosage and the timing of the IV magnesium regimen, which in some trials also included anti-clotting drugs. The evidence produced by this review does not support continued use of IV magnesium. Other effective treatments (aspirin, beta-blockers) should be used to treat heart attack.
A systematic review of the data from randomised controlled trials provides no evidence that routine thyroid hormone therapy is effective in preventing problems in preterm babies or improves their developmental outcomes. Thyroid hormones are needed for the normal growth and maturity of the central nervous system, as well as the heart and lungs. Children born without sufficient thyroid hormones can develop serious mental retardation. It is believed that low levels of thyroid hormones in the first few weeks after birth (transient hyperthyroxinaemia) in preterm babies born before 34 weeks may contribute to this abnormal development. The review of trials found no evidence that using thyroid hormones routinely in preterm babies is effective in reducing the risk of problems caused by transiently low levels of thyroid hormones.
Abdominal pain-related functional gastrointestinal disorders (FGIDs) are common in childhood and adolescence. In most cases no medical reason for the pain can be found. Various drug treatment approaches for the different types of abdominal pain-related FGIDs exist. These drug treatments include: prokinetics and antisecretory agents for functional dyspepsia; pizotifen, propranolol, cyproheptadine or sumatriptane for abdominal migraine; and antispasmodic and antidiarrhoeal regimen for irritable bowel syndrome. Antidepressants have been shown to be effective in some studies of adults with functional gastrointestinal disorders. As a result young patients with similar complaints are sometimes treated with antidepressants. The purpose of this review was to examine the evidence assessing the advantages and disadvantages of such an approach. Only two studies met the inclusion criteria. Both of these studies were randomised controlled trials and assessed the effectiveness and safety of amitriptyline in children with FGIDs. Amitriptyline is a first generation antidepressant (tricyclic antidepressant). Amitriptyline is no longer an agent of first choice for the treatment of depressive disorders because of potentially serious side effects including overdose. Amitriptyline has not been approved for the treatment of functional abdominal pain in children or adolescents. The larger study (n = 90) showed no difference in the proportion of patients feeling better between the treatment - and the placebo (sugar pill) groups. Side effects were mild and included fatigue, rash and headache and dizziness.The authors of the other, much smaller study (n = 33) reported a significant improvement in overall quality of life and a reduction in pain for specific areas of the abdomen and certain follow up times. However, the results of this study should be interpreted with caution due to poor methodological quality and the small number of patients enrolled. Amitriptyline does not appear to provide any benefit for the treatment of FGIDs in children and adolescents. At present, the evidence for the treatment of children and adolescents with abdominal pain-related diseases with antidepressants does not support the use of antidepressant agents in this group of patients. We suggest considering alternative treatments that are supported by stronger evidence. There is need for larger, well-conducted trials with adequate patient relevant outcomes such as quality of life and pain relief to provide more information regarding this common condition.
We searched a wide range of electronic medical databases up to July 2015 for relevant studies. We included studies written in any language that included adults and compared treatment with acupuncture for cancer pain against no treatment, or usual treatment, or sham acupuncture, or other treatments. Since we were only interested in robust research, we restricted our search to randomised controlled trials (in which participants are randomly allocated to the methods being tested). We found five studies (with a total of 285 participants) that compared acupuncture against either sham acupuncture or pain-killing medicines. All five identified studies had small sample sizes, which reduces the quality of their evidence. One pilot study was well designed, but was too small to identify any differences in pain in women with ovarian cancer after electroacupuncture or a sham treatment. One study found that auricular (ear) acupuncture reduced cancer pain when compared with sham auricular acupuncture that was given at non-acupuncture points. However, the people in the sham acupuncture group could have been aware that they were not in the real acupuncture group and this could have affected the level of pain they reported. Another study found a difference between an electroacupuncture group and sham group in people with pancreatic cancer but again, there was no reported attempt to conceal which group people were in. One study found that acupuncture was as effective as pain-killing medication, and one study found that acupuncture was more effective than medication, but both studies were poorly designed and the study reports lacked detail. None of the studies described in this review were big enough to produce reliable results. None of the studies reported any harm to the participants. We conclude that there is insufficient evidence to judge whether acupuncture is effective in relieving cancer pain in adults. Larger, well-designed studies are needed to provide evidence in this area.
We included randomised controlled trials comparing any antibiotic therapy with placebo or no treatment in people with acute bronchitis or acute productive cough and no underlying chronic lung condition. We included 17 trials with 5099 participants. Co-treatments with other medications to relieve symptoms were allowed if they were given to all participants in the study. Our evidence is current to 13 January, 2017. We found limited evidence of clinical benefit to support the use of antibiotics for acute bronchitis. Some people treated with antibiotics recovered a bit more quickly with reduced cough-related outcomes. However, this difference may not be of practical importance as it amounted to a difference of half a day over an 8- to 10-day period. There was a small but significant increase in adverse side effects in people treated with antibiotics. The most commonly reported side effects included nausea, vomiting, diarrhoea, headache, and rash. This review suggests that there is limited benefit to the patient in using antibiotics for acute bronchitis in otherwise healthy individuals. More research is needed on the effects of using antibiotics for acute bronchitis in frail, elderly people with multiple chronic conditions who may not have been included in the existing trials. Antibiotic use needs to be considered in the context of the potential side effects, medicalisation for a self limiting condition, cost of antibiotic treatment, and in particular associated population-level harms due to increasing antibiotic resistance. The quality of these trials was generally good, particularly for more recent studies.
We found the overall quality of the evidence to be very low. The trial itself was only published as an abstract from a conference which did not include numerical data and it was not published as a full report. This meant that we do not know many details about the trial. We thought that the overall risk of bias was unclear, as the trial authors did not describe how participants were put into the treatment groups, whether any participants dropped out or whether the planned outcomes were the same as the reported outcomes. The trial also had a very small number of participants and a limited age range, making it difficult to draw conclusions about the relevance of the treatment for all people with cystic fibrosis.
The review found two studies. The first study took place in India. Here, families, teachers, children and village leaders were encouraged to attend information meetings where they were given information about childhood vaccination and could ask questions. Posters and leaflets were also distributed in the community. The second study was from Pakistan. Here, people who were considered to be trusted in the community were invited to meetings where they discussed the current rates of vaccine coverage in their community and the costs and benefits of childhood vaccination. They were also asked to develop local action plans, to share the information they had been given and continue the discussions with households in their communities. What happens when members of the community are informed or educated about vaccines? The studies showed that community-based information or education: - may improve knowledge of vaccines or vaccine-preventable diseases; - probably increases the number of children who get vaccinated (both the study in India and the study in Pakistan showed that there is probably an increase in the number of vaccinated children); - may make little or no difference to the involvement of mothers in decision-making about vaccination; - may change attitudes in favour of vaccination among parents with young children; We assessed all of this evidence to be of low or moderate certainty. The studies did not assess whether this type of information or education led to better knowledge among participants about vaccine service delivery or increased their confidence in the decision made. Nor did the studies assess how much this information and education cost or whether it led to any unintended harms.
The recommendations in this review are based on a critical analysis of the available evidence in the medical literature. We found only one, relatively small, randomised controlled trial of steroids in TON, which included 31 participants within seven days of their initial injury. These participants received either high dose intravenous steroids (n = 16) or placebo (n = 15). At three months follow-up, no significant difference in best corrected visual acuity was found between these two groups. There is a relatively high rate of spontaneous visual recovery in TON and no convincing data that steroids provide any additional benefit over observation alone. Each case needs to be assessed on an individual basis and the patient needs to be made fully aware of the possibility of a serious adverse reaction, although rare, to steroids. Furthermore, recent studies have highlighted possible detrimental effects of steroids when used in brain and spinal cord injuries and these new lines of evidence need to be considered seriously.
We performed a search of the available scientific literature to find all trial evidence to assess this question. Fifty-six trials were found. Fifty-three trials involved thiazide diuretics (92% with the drug hydrochlorothiazide) and included a total of 15310 participants. Adding a thiazide to another anti-hypertensive drug further reduces the BP by an additional 6/3 mmHg when given at the starting dose and reduces BP by 8/4 mmHg at 2 times the starting dose. This is approximately the same effect as when the drugs are used alone. A good estimate of the harms associated with diuretics cannot be estimated in this review because of the lack of reporting and the short duration of the trials.
The progestogen-releasing (levonorgestrel) intrauterine system (LNG-IUS) is a device placed inside the uterus that releases the hormone progesterone and can cause endometrial suppression. In this review, three randomised controlled studies were included. Two randomised controlled studies included 131 women and evaluated the beneficial and harmful effects of the LNG-IUS compared with hysterectomy or a low dose combined oral contraceptive (COC). However, the results were from only one study that compared 29 women with an LNG-IUS versus 29 women with COC for treating uterine fibroids. The LNG-IUS appeared to reduce menstrual blood loss and increase haemoglobin levels in premenopausal women with uterine fibroids. Reduction of fibroid size was not significant. In one study that included 56 women treated with preoperative oral progestogens (lynestrenol) compared with gonadotropin-releasing hormone (GnRH) agonist, the uterine fibroid size was not different. There was no randomised controlled study of DMPA to treat uterine fibroids. The included studies were of poor quality and had small numbers of participants. Indeed, the authors did not recommend the use of progestogens or progestogen-releasing intrauterine systems in treating premenopausal women with uterine fibroids. More high quality randomized controlled studies evaluating progestogens or progestogen-releasing intrauterine systems for treating uterine fibroids that have an adequate sample size are needed.
The purpose of this review was to assess which of these two medications was the best for initial treatment for people living with HIV, and through our search we identified nine randomised controlled trials. Overall, these studies showed no critical difference between d4T and AZT. Future studies and recommendations should focus on specific toxicities and tolerability when comparing these two medications.
We included eight studies with 510 participants (443 boys, 67 girls) in our review. Participants in these studies were children with both ADHD and a chronic tic disorder. The included studies evaluated several different medications for ADHD, including stimulants (methylphenidate, dextroamphetamine) and non-stimulants (clonidine, guanfacine, desipramine, atomoxetine, and deprenyl). All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding for the study. The trials in this review suggested that several stimulant and non-stimulant medications may improve ADHD symptoms in children with ADHD and tics. At high doses, dextroamphetamine may initially worsen tics in some children, and dose increases of both dextroamphetamine and methylphenidate may be limited due to tic exacerbation. However, for most children, both tics and ADHD symptoms can improve with use of stimulant medications. There is low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine, and deprenyl in the treatment of ADHD in children with tics. The evidence was limited by the small number of trials, small number of participants, and risk of bias of the included studies.
We found seven trials studying antibiotic treatments for neurological Lyme disease. All but one trial compared different antibiotics. The other trial compared the treatment effects of oral amoxicillin to placebo following initial ceftriaxone treatment. The trials included 450 Europeans. The antibiotics tested were penicillin G, doxycycline, ceftriaxone, and cefotaxime. One of the trials involved children only, while the others included mostly adults. We only selected studies in which treatment allocation was determined by chance (randomly), as such studies provide the best information for comparing the effects of different treatments. Most studies were not blinded (meaning that those taking part and the study staff knew the treatment being given). We could not find any studies of antibiotic treatments for neurological Lyme disease from the United States. No studies assessed the effects of delaying the start of treatment. The seven studies were too different for their results to be combined, so we analyzed them individually. None of the studies provided clear evidence that one antibiotic was better than another. One study failed to find evidence that a second and longer treatment with an oral antibiotic (amoxicillin) offered any extra benefit following initial intravenous treatment with ceftriaxone. As none of the other studies used a dummy treatment (placebo), the extra benefit offered by antibiotic treatment over recovery that occurs naturally is unknown. In general, the treatment was tolerated well, although the quality of adverse event reporting in most studies appeared to be low. The results indicate that treatment with any of the four antibiotics produced similarly good outcomes for treatment of neurological Lyme disease in Europe. A second treatment with amoxicillin does not appear to provide added benefit to ceftriaxone. We found no trials of antibiotics for treatment of neurological Lyme disease in the United States. The evidence is current to October 2016.
This review compared three asthma medications, salmeterol, formoterol (both long acting beta-agonists) and theophylline. These medications are used to help control symptoms of asthma, especially those which occur during the night. This review found that salmeterol showed a greater improvement in lung function, and reduced the need for extra short-term inhalers in the day and the night. Salmeterol and formoterol are less likely to produce side-effects (such as headaches and nausea) when compared to theophylline.
This review showed that antiplatelet drugs can also reduce the risk of stroke in patients undergoing carotid endarterectomy. There was limited information on bleeding risk. The review's conclusions supported the routine use of antiplatelet drugs such as aspirin in patients having carotid endarterectomy.
We found ten studies with 1592 people to include in the review. On average, the studies lasted only 12 weeks, although one study ran for nine months. Each of them used a set of formal criteria to diagnose both depression and dementia and compared an antidepressant against a dummy pill (placebo). The older studies used more old-fashioned antidepressants (imipramine, clomipramine, and moclobemide) and the newer studies used more modern ones, such as venlafaxine, mirtazapine and so-called SSRI antidepressants (sertraline, fluoxetine, citalopram and escitalopram). The people taking part in the studies had an average age of 75 and they had mild or moderate dementia. With the exception of two studies, they were being treated as outpatients. We found that there was little or no difference in scores on depression rating scales between people treated with antidepressants and those treated with placebo for 12 weeks. The evidence to support this finding was of high quality, which suggests that further research is unlikely to find a different result. There was probably also little or no difference after six to nine months of treatment. Another way to assess the effect of antidepressants is to count the number of people in the antidepressant and placebo groups who show significant clinical improvement (response) or who recover from depression (remission). There was low-quality evidence on the number of people showing a significant clinical improvement and the result was imprecise so we were unable to be sure of any effect on this measure. People taking an antidepressant were probably more likely to recover from depression than were those taking placebo (antidepressant: 40%, placebo: 21.7%). There was moderate-quality evidence for this finding, so it is possible that further research could find a different result. We found that antidepressants did not affect the ability to manage daily activities and probably had little or no effect on a test of cognitive function (which includes attention, memory, and language). People taking an antidepressant were probably more likely to drop out of treatment and to have at least one unwanted side effect. The quality of the evidence varied, mainly due to poorly conducted studies and problems with the relevance of the outcome measures used. This should be taken into consideration when interpreting the different results on depression rating scales and recovery rates, as evidence was of a higher quality for the former than for the latter. Another major problem is that side effects are very rarely well-reported in studies. Therefore, further research will still be useful to reach conclusions that are more reliable and can better help doctors and patients to know what works for whom.
We included four studies involving 302 patients with idiopathic non-allergic rhinitis. All the included studies described patients with moderately severe idiopathic non-allergic rhinitis, who were between the ages of 16 and 65. The studies had a follow-up ranging from four to 38 weeks after treatment. Individually, the studies reported that the overall function of the nose in patients with non-allergic rhinitis improved when treated with capsaicin compared to placebo. Capsaicin also seems to work better than another common type of nasal medication, budesonide (a steroid). The best knowledge that we have on capsaicin treatment supports giving it five times in one day, and to use doses of at least 4 micrograms in each puff. We could not combine the results together. The included studies did not have sufficient information to allow us to draw a conclusion about side effects. We also wanted to include other outcomes (e.g. quality of life measures, treatment dropouts, endoscopic scores, turbinate or mucosal size, cost of therapy), but none of these were measured or reported in the included studies. Overall, we judged the quality of the evidence to be of low to moderate quality. The evidence is up to date to June 2015. Given that many other options do not work well in non-allergic rhinitis, capsaicin is a reasonable option to try under physician supervision.
The patients included in the 13 trials we identified were adults with acute leukemia or solid organ transplantation and children with acute leukemia. This review of randomised controlled trials (RCTs) found that prophylaxis with trimethoprim/sulfamethoxazole, an antibiotic effective against PCP, significantly reduced the occurrence of PCP by 85%. We found no evidence for a reduction in all cause mortality. Confidence in the results for PCP was moderate to high, while for mortality it was low due to paucity of data. Preventive treatment was not associated with an increased rate of adverse events. Trimethoprim/sulfamethoxazole may be administered thrice weekly as effectively as once daily. Based on our results, the number of people that need to be treated with trimethoprim/sulfamethoxazole for a prolonged period of time (ranging between several weeks to three years in the included trials) in order to prevent one episode of PCP infection was 19; when PCP infection occurs at a rate of about 6% without prophylaxis. Given the low rate of adverse events, prophylaxis should be considered for patients at similar risk of PCP.
Three trials (N = 1421) were included in the meta-analysis assessing the efficacy of chemotherapy plus rituximab compared to chemotherapy without further therapy. The meta-analysis showed for patients receiving additional rituximab a statistically significant improvement of overall survival and a longer time without progression of the disease. Treatment with rituximab caused more adverse events, but this did not lead to a statistically significant difference regarding death caused by treatment. However, patients who were treated within these trials did not suffer from other severe health problems aside from CLL; therefore, it remains unclear whether patients with severe co-morbidities will benefit from this treatment option. In summary, this meta-analysis showed that patients receiving chemotherapy plus rituximab benefited in terms of survival compared to those with chemotherapy alone. Therefore, it supports the recommendation of rituximab in combination with fludarabine and cyclophosphamide as an option for the first-line treatment as well as for people with relapsed or refractory CLL. Further research should focus on the evaluation of benefits of adding rituximab to other chemotherapy regimens than fludarabine with cyclophosphamide in the therapy of previously untreated, relapsed or refractory patients. It should also assess whether patients with serious co-morbidities will benefit from the addition of rituximab to chemotherapy. The available evidence regarding assessed comparisons from four other trials was not sufficient to deduct final conclusions.Two trials evaluated polychemotherapy in combination with rituximab versus alemtuzumab respectively. One trial evaluated two different rituximab schedules: rituximab given concurrently with primary treatment plus rituximab therapy given subsequently to the primary treatment versus primary treatment alone with subsequent administration of rituximab. One trial investigated two different dosages (500 mg and 1000 mg) of ofatumumab in addition to fludarabine with cyclophosphamide. Randomised Controlled Trials (RCTs) are needed to determine the clinical effects of novel anti-CD20 antibodies, such as ofatumumab or GA101, compared to rituximab. We are aware of 16 ongoing studies, including three trials comparing ofatumumab with or without additional chemotherapy versus no treatment. The findings of these trials will be included in an update of this review and could lead to different conclusions and may allow a judgement on general efficacy and safety of monoclonal anti-CD20 antibody in the treatment of CLL.
In April 2018, we looked for studies including adults or children with bronchiectasis that randomly allocated participants to receive one antibiotic or another by the same method of administration. We found only four studies, and they were very small. In total, they included 138 participants. This small sample makes it very difficult to draw clear conclusions. Four randomised trials were eligible for inclusion in this systematic review. None of the included studies reported information on flare-ups (exacerbations). Included studies reported no deaths and no serious adverse events. Treatment failures were fewer with fluoroquinolone antibiotics than with amoxicillin antibiotics. Reviewers considered the quality of the evidence provided by the four small included studies to be low or very low. Fluoroquinolone antibiotics may be more successful than amoxicillin antibiotics in treating exacerbations, but this finding is based on low-quality evidence. More evidence from high-quality clinical trials of short-term and long-term treatment with antibiotics is needed if clear conclusions are to be reached on the benefits of one antibiotic over another for people with bronchiectasis.
In view of the importance of the functions performed by law enforcement officers, and the fact that there is no definitive approach to deal with psychological problems they may develop, a systematic review of the evidence is needed to determine the effectiveness of psychosocial interventions in preventing these problems in this select population. We found ten randomised trials, but not of all these contributed useful data for this review and quantitative meta-analyses were not possible. No data on adverse effects were available. The available evidence is, therefore, limited to the analysis of single, small and low quality trials. This suggests that police officers may benefit from psychosocial interventions in terms of psychological symptoms and physical symptoms. Further well-designed trials of psychosocial interventions to enhance the psychological health of police officers are required. Trials of organisation-based interventions are also needed.
In February 2012, we did a computer search for studies of cervical caps. We wrote to manufacturers and researchers for information about other trials. We included randomized controlled trials that compared a cervical cap with a diaphragm. We found two trials that compared the cervical cap with the diaphragm. Two types of cervical caps were studied: the Prentif cap and the FemCap. The Prentif cap prevented pregnancy as well as the diaphragm, but the FemCap did not. Women who used the Prentif cap had more abnormal changes in the cervix than diaphragm users. The FemCap users did not have more abnormal changes than the diaphragm users. Many women from both groups dropped out early from the two trials. Similar numbers of FemCap users and diaphragm users reported liking their assigned method. The Prentif cap worked as well as the diaphragm to prevent pregnancy. The FemCap did not prevent pregnancy as well as the diaphragm. Both cervical caps appear to be medically safe.
We carried out a systematic review and searched for published and unpublished randomised controlled trials (RCTs) that compared open and laparoscopically assisted vaginal methods of performing radical hysterectomy in women with early cervical cancer. The evidence is current to July 2013. We found only one relevant trial. It included only 13 women; seven had a laparoscopically assisted radical vaginal hysterectomy (LARVH) and six had radical abdominal hysterectomy (RAH). Women who underwent LARVH appeared to have less blood loss, shorter hospital stay and less requirement for pain medication compared with those who underwent RAH. There was no statistically significant difference in the risk of complications related to the operation in women who underwent LARVH and RAH. However, RAH had a significantly shorter operation time compared with LARVH. The trial did not assess overall survival and progression-free survival (PFS; the time that a woman lives with the cancer but does not get worse) or quality of life (QoL) as the main focus of the trial was to examine short-term complications. Due to the small number of cases and the short-term scope of the trial, we were unable to reach any definite conclusions about the relative benefits and harms of the two forms of treatment and we were unable to identify subgroups of women who are likely to benefit from one treatment or the other.
There was no significant difference between the sedation techniques as regards safety. There were no deaths in the trials and the number of major complications, such as lack of oxygen (hypoxaemia) and low blood pressure (hypotension), was comparable in both techniques. There was no difference in patient satisfaction in either group. However, the recovery of patients who received propofol was significantly better than for those who had received midazolam and meperidine for the procedure. In conclusion, patients undergoing ERCP procedures under propofol sedation recover faster and better than those patients receiving midazolam and meperidine sedation. This would make propofol the preferred choice for these procedures as there was no difference in the safety of either technique. Further research should focus on the safety of the sedative techniques and involve anaesthesia personnel in the administration of the sedation.
We identified 37 trials conducted between 1969 and 1999. The evidence is current up to April 2015. Trials were conducted in Australia, Belgium, Brazil, Canada, Denmark, France, Germany, Italy, New Zealand, Northern Ireland, Norway, Poland, Sweden, Switzerland, The Netherlands, United Kingdom and United States of America and included 11,948 participants. Trials were conducted in pre-hospital and in-hospital settings and included individuals with or without proved acute myocardial infarction. Some trials did not limit results to acute myocardial infarction only. Lidocaine was given by intravenous (bolus and/or infusion) and intramuscular (alone or in combination with intravenous dosage) routes. Overall, trials included small sample sizes and reported low numbers of events. All trials had high risk of bias. Ten trials were sponsored by the pharmaceutical industry. In people who had known or suspected heart attack, we found that lidocaine compared with placebo, no intervention or any other antiarrhythmic drug had very small or no effects on death, cardiac death and ventricular fibrillation. Our confidence in the results of this review is low because the included trials that we synthesised were of low quality (overestimation of benefits and underestimation of harms) and were conducted with a small number of participants, leading to imprecision of results.
This evidence is current to February 2016. Males and females of all ages diagnosed with PH were included in this review. We selected only randomised clinical trials. All trials used a comparison to no treatment. Trial durations ranged from 12 to 16 weeks. This review involves five trials on 962 participants. All included studies were sponsored by the maker of the drug. Soluble guanylate cyclase stimulators appear to reduce lung pressures and improve exercise capacity in PAH and recurrent or inoperable CTEPH, but not in PH due to left heart disease. It is uncertain if these drugs have an effect on death rates and general health decline, or if they may be associated with serious side effects. There is evidence that suggests these drugs should not be taken at the same time as phosphodiesterase-V inhibitors. One outcome was considered to be high quality according to the GRADE scoring system. Two were considered moderate strength and eight outcomes were considered low or very low strength. This means the results reported may not represent the true effect.
A total of three trials including 255 patients qualified for this review of randomised clinical trials. Two trials randomised 150 patients in total to absorbable clips (n = 75) and non-absorbable clips (n = 75). A third trial randomised a total of 105 patients to absorbable ligatures (n = 53) and non-absorbable clips (n = 52). All three trials were of high risk of bias. There was no difference in the morbidity between the groups. The operating time was 12 minutes longer in the absorbable ligature group than in the group randomised to non-absorbable clips.The duration and method of follow-up were not adequate to determine the incidence of long-term complications. We are unable to determine the benefits and harms of different methods of cystic duct occlusion because of the small sample size, short period of follow-up, and lack of reporting of important outcomes in the included trials. New trials with long periods of follow-up and assessing the important outcomes are necessary. Such trials should be designed well to decrease the risk of random errors and systematic errors.
We found two randomised clinical trials (types of studies in which participants are assigned to treatment group using a random method) involving a total of 154 adult participants who received either a non-selective shunt surgery, a selective shunt surgery, or devascularisation surgery. However, the design of both trials was of insufficient quality, as the numbers of trial participants were small, and some participant information was lacking. One of the trials was funded by an institutional grant, and how funding was obtained for the other trial was not clear. We assessed both trials as at high risk of bias. There were no significant differences in the number of participants who had repeat bleeding, adverse effects of treatment, or deaths between the shunt surgery and the devascularisation group, but participants who had devascularisation were less likely to suffer encephalopathy (disease of the brain due to damage from toxins produced by the liver). Neither of the trials addressed quality of life after treatment. Given the very low certainty of the evidence due to the way the clinical trials were performed, limited trial data and trial participants, we were unable to determine whether one treatment is better than the other. We suggest that future trials include a sufficient number of randomised participants to be able to obtain meaningful results on patient-relevant outcomes and allow objective comparison of these two surgery types.
This systematic review evaluated the efficacy and tolerability of second-generation antipsychotics in the treatment of anxiety disorders. We found eleven randomised placebo-controlled trials, comparing quetiapine, olanzapine and risperidone with placebo and antidepressants. The vast majority of the available data was on quetiapine (> 3000 participants). Participants with generalised anxiety disorder responded significantly better to quetiapine than to placebo, measured as a reduction in the Hamilton Anxiety Scale (HAM-A). Participants treated with quetiapine were more likely to drop out due to adverse events, to gain weight, to suffer from sedation or to suffer from extrapyramidal side effects. The evidence on the other second-generation antipsychotics is currently too limited to draw any conclusions.
Sixteen relevant studies were identified and included in this review. They have researched a variety of different interventions, having different purposes, and so a single overall definite conclusion cannot be made. However the authors cautiously conclude that Cognitive Behavioural Therapy, a therapy that addresses thoughts and behaviours, can help people with MS adjust to, and cope with, having MS, and can help them if they get depressed. Psychological interventions can potentially help people with MS in many ways, including the management of symptoms such as pain and fatigue. Additional studies are needed, particularly those that include larger numbers of people.
Only three trials could be included in this review. One of these trials was conducted in Shanghai, China. It compared screening twice yearly with ultrasound and alpha-foetoprotein against no screening. The trial has a high risk of systematic errors (bias) and several published reports of the trial provide different results. Another trial was conducted in Toronto, Canada. It compared screening with alpha-foetoprotein and ultrasound versus screening with alpha-foetoprotein alone. This trial had too few participants. As there were no participants who were not screened, we cannot assess whether screening is effective in reducing mortality. The remaining trial was published as an abstract only. It was designed to determine the optimal time interval for screening using alpha fetoprotein and ultrasound. The cumulative four-year survival was not significantly different between the two studied screening intervals of four months and 12 months. Thus, to date, there is insufficient evidence regarding screening for liver cancer among patients with chronic hepatitis B infection.
This review assessed information from 10 studies which used celecoxib for acute pain. Just over 3 in 10 people (33%) taking celecoxib 200 mg, and over 4 in 10 (43%) taking celecoxib 400 mg, experienced good pain relief (at least 50%) compared to about 1 in 10 (range 1% to 11%) with placebo. Comparing the results of the different studies showed that the 200 mg dose of celecoxib was at least as good as aspirin 600 to 650 mg and paracetamol (acetaminophen) 1000 mg for relieving postoperative pain, while a 400 mg dose was at least as good as ibuprofen 400 mg. The number of people who experienced negative (adverse) reactions was similar for celecoxib and placebo, and stopping the medication due to these adverse reactions also occurred at similar rates. One serious adverse event, muscle breakdown (rhabdomyolysis), was probably related to celecoxib.
We searched for evidence in July 2017 and identified only one study published in 1989. The study included 393 women undergoing either vacuum or forceps delivery comparing those receiving the antibiotic cefotetan with those women who received no treatment. There were no differences between the two groups of women in terms of age, previous pregnancies and other important characteristics. The only two outcomes reported in the trial were infection of the uterus (endometritis) and length of hospital stay. The trial reported that seven women had an infection of the uterus (endometritis) in the group that did not receive any antibiotics. No woman in the antibiotic group was reported to have an infection. Giving antibiotics had no effect on length of hospital stay for the mother for either group. The quality of the evidence for these two outcomes was assessed as being low: the evidence comes from a single trial, which included a very small number of women and reported on only two outcomes. Evidence from this single trial suggests that antibiotic prophylaxis may lead to little or no difference in endometritis or maternal length of stay. There were no data on any other outcomes to evaluate the impact of antibiotics for preventing infection after operative vaginal delivery. Future research on antibiotic prophylaxis for operative vaginal delivery is needed to provide evidence on whether it is a useful intervention.
This review did not find any high quality research evidence showing that HBOT is beneficial for wound healing. Two poor quality studies suggested benefits associated with HBOT. The first, in patients with crush injuries, showed improved wound healing and fewer adverse outcomes. The second reported improved survival of split skin grafts in people with burn wounds. Two trials reported no benefits associated with HBOT for either skin grafting or free flap surgery. Further, better quality research is needed to determine the effects of HBOT on wound healing.
No clear evidence from available RCTs suggests that any of the measures used to protect the kidneys during the perioperative period are beneficial. These findings held true in 14 studies of patients with pre-existing renal damage and in 24 studies that were considered of good methodological quality. The primary outcomes of these studies were mortality and acute renal injury. Reported mortality in studies with low risk of bias was not different between intervention and control groups (odds ratio (OR) 1.01, 95% confidence interval (CI) 0.52 to 1.97) or for acute renal injury (OR 1.05, 95% CI 0.55 to 2.03). The summary of findings revealed a similar picture. So we conclude that evidence suggests that none of the interventions used currently are helpful in protecting the kidneys during the perioperative period, nor do they cause increased harm.
This review included six studies involving over 1345 TBAs, more than 32,000 women and approximately 57,000 births and examined the effect of TBA training, or additional training, on TBA behaviour and on pregnancy outcomes. We conclude that while there are a few more studies meeting the inclusion criteria and the results are promising for some outcomes, more evidence is needed to establish the potential of TBA training to improve peri-neonatal mortality. A lack of contrast in training in the intervention and control clusters and an insufficient number of studies may have contributed to the lack of observed differences in maternal deaths and deaths of their babies (early neonatal deaths).
A review of studies concluded that helmets reduce the risk of head injury by around 69% and death by around 42%. There is, so far, insufficient evidence to compare the effectiveness of different types of helmet. Some studies have suggested that helmets may protect against facial injury and that they have no effect on neck injury, but more research is required for a conclusive answer. The review supports the view that helmet use should be actively encouraged worldwide for rider safety.
The review located 12 relevant randomised controlled studies looking at the effect of stretching before or after physical activity on muscle soreness. Eleven studies were small with between 10 to 30 people being allocated stretching exercises. In contrast, one study was large with 2337 participants, 1220 of whom were in the stretching group. Ten studies were conducted in laboratories using standardised exercises. The only two studies, which included the only large study, were so-called field-based studies. These examined the effect of stretching on muscle soreness associated with self-selected physical activity. The studies were of low to moderate quality. Some of the studies examined the effects of stretching before physical activity, some examined the effects of stretching after physical activity, and some examined effects of stretching both before and after physical activity. The studies produced very consistent findings. They showed there was little or no effect of stretching on the muscle soreness experienced in the week after the physical activity.
We included one small study on 25 people with chronic lung disease. Of those 25, only eight people had bronchiectasis. Other individuals had chronic bronchitis of diffuse panbronchiolitis and were at risk for bronchiectasis. However, we must remember when interpreting the results that not all study participants had bronchiectasis. Overall, the small study reported improvement in sputum production and dyspnoea (shortness of breath) in adults with chronic lung disease (chronic bronchitis, bronchiectasis or diffuse panbronchiolitis) who received inhaled indomethacin compared with placebo. Researchers observed no significant improvement in lung function (forced expiratory volume in one second (FEV1) and vital capacity (VC)) and reported no adverse events. Conclusions The small scale of this study and collective analysis of data from the three disease states made it difficult for review authors to draw solid conclusions on the benefit of using NSAIDs to treat adults with bronchiectasis. Review authors identified no studies examining the use of NSAIDs in children with bronchiectasis.
We searched for all relevant research, found six studies and assessed the quality of each study. We pooled their results where possible to draw our overall conclusions. Some of the original researchers provided additional information beyond that in their published studies. However, most of the research was conducted more than 10 years ago and only the published work was available to us. We found that all six studies examined the therapy approach of practising perceptual activities (e.g. puzzles and tasks that involve processing sensory information) with stroke patients. No study examined whether the therapy provided benefits past six month in terms of the level of independence in undertaking everyday activities. On the basis of existing research evidence, the benefit or harm of therapy for adults who experience difficulty processing sensory information after stroke or brain injury remains unknown. People with perceptual problems should continue to be offered rehabilitation as recommended in guidelines intended for healthcare practitioners. Future studies should be large enough to be conclusive and should look at the longer-term effects of therapy, including independence in doing everyday activities, emotions, outcome for family caregivers and potential harmful effects.
A review of the literature was undertaken to determine how effective rectal 5-ASA (e.g. enemas, suppositories or foam) is for treating distal UC. Thirty-eight studies met the criteria for inclusion in the review. Pooled results from these studies show that rectal 5-ASA is superior to placebo (fake suppositories, enemas or foam) for improving symptoms, improving the appearance of the bowel lining at colonoscopy, and improving the appearance of biopsies of the bowel examined microscopically. Rectal 5-ASA is also superior to rectal steroids for improving symptoms. Side effects were generally mild in nature and included abdominal pain or distention, nausea and anal discomfort or irritation. From these results, it was concluded that rectal 5-ASA should be a first-line treatment for patients with mild to moderately active distal UC.
Twenty-one randomised controlled studies with a total of 3286 participants were included. The data were combined in an analysis to get an overall result. All types of antispasmodics were given at the beginning of established labour. They decreased the first stage of labour, the time from beginning of labour until the baby is about to be born, by 49 to 98 minutes, as well as the total duration of labour, from the beginning of labour until the delivery of the afterbirth, by 49 to 121 minutes. The drugs did not affect the number of women requiring emergency caesarean sections and did not have serious side effects for either mother or her baby. The most commonly reported adverse events for the mothers were fast heart rates and mouth dryness, but since both maternal and neonatal adverse events were poorly reported, more information is needed to make conclusions about the safety of these drugs during labour. The included studies were mostly of poor quality and good studies are needed to assess what happens when these drugs are given to women whose labour is already prolonged.
After searching for relevant studies, we found two studies with a combined total of 288 participants to be included in this review of evidence. One study compared two forms of the anticoagulant heparin. Low molecular weight heparin offered no significant improvement over unfractionated heparin in the prevention of DVT. Furthermore neither drug caused bleeding. However, in this study both the participants and study personnel were aware of which treatment was being administered. This may have biased the results. It is unclear if other bias was introduced in the study because the process of randomly allocating treatment was not adequately described. The second study concluded that heparin was not more effective in preventing a PE than placebo whether the amputation was above or below the knee. Bleeding occurred in less than 10% of each treatment group but the study authors did not report specific numbers and therefore this could not be analysed. This study did not report the methods used to conceal how treatment was allocated but it was judged to be free from other sources of bias. This review found that there are too few trials to determine the most effective strategy in preventing VTE in people undergoing amputation of the lower limb. No study looked at mechanical forms of preventing VTE, such as compression devices, and therefore it is not possible to make any conclusions about these. Further good quality and large-scale studies are required.
Studies in animals have shown that lowering the body temperature can help to protect the brain cells in circumstances when the blood supply to the cells is compromised. Similarly, studies in humans who have been resuscitated after their heart stopped beating have shown that lowering their body temperature helps to reduce brain damage. The purpose of this updated version of a previous review of the same title was to determine whether cooling patients who were having brain surgery reduced death and serious disability, or was associated with increased risk of harm. A detailed search of the available literature up until May 2014 identified four eligible studies that included a total of 1219 participants. Their results were combined to answer these questions. No evidence was found that cooling patients who are having brain operations reduced the risk of death or severe disability, or produced significant harm.
However, there is some concern about the reliability of the evidence due to not all trials reporting allergy outcomes and trials not reporting the outcome for all infants. Reactions to foods and allergies (including asthma, eczema and hay fever) are common and may be increasing. Many infants become sensitised to foods, including infant formula, through their gastrointestinal tract, a process that may be affected by the composition of the intestinal bacteria. Attempts to promote the growth of normal gastrointestinal bacteria and prevent sensitisation to foods have included the addition of prebiotic to infant formula. Prebiotics are nondigestible food components that help by selectively stimulating the growth or activity of 'healthy' bacteria in the colon. This review found some evidence that a prebiotic supplement added to infant feeds may prevent eczema in infants up to two years of age. It is unclear whether the use of prebiotic should be restricted to infants at high risk of allergy or may have an effect in low risk populations; or whether it may have an effect on other allergic diseases including asthma. However, further research is needed to confirm the findings before routine use of prebiotics can be recommended for prevention of allergy.
We identified 10 studies (nine trials and one follow-up study) up to December 2014. In total, the studies involved over 1100 primary care doctors and around 492,000 patients. The intervention was different in each study. Six of the studies involved training clinicians (mostly primary care doctors) in communication skills that are needed to facilitate shared decision making. In three studies, as well as training doctors in these skills, patients were also given written information about antibiotics for acute respiratory infections. All included trials received funding from government sources. No studies declared a conflict of interest. Interventions that aim to facilitate shared decision making significantly reduce antibiotic prescribing for acute respiratory infections in primary care, without a decrease in patients' satisfaction with the consultation, or an increase in repeat consultations for the same illness. There was not enough information to decide whether shared decision making affects other clinically adverse secondary outcomes, measures of clinician and patient involvement in sharing decision making, or antibiotic resistance. We rated the quality of the evidence as moderate or low for all outcomes.
We identified five RCTs with a total of 827 participants. Seven hundred thirty participants (384 received continuous sutures and 346 interrupted sutures) provided data for this review. Participants had abdominal or groin operations. The only outcomes reported were, superficial surgical site infection, superficial wound breakdown and length of hospital stay. No other important outcomes, including quality of life, long-term patient outcomes and use of healthcare resources, were reported. Approximately 6% of participants developed superficial surgical site infection, but there was no significant difference between the two groups in the proportion of participants who developed these. Approximately 4% of participants developed superficial wound breakdown. The proportion of participants with this problem in the continuous suture group was approximately one-tenth of that in the interrupted suture group. Most wound breakdowns occurred in two trials that used absorbable sutures for continuous suturing and non-absorbable sutures for interrupted suturing. Non-absorbable sutures are removed seven to nine days after surgery, but absorbable sutures are not removed, and so support the wound for longer - which may account for the difference in distribution of this problem between groups. There was no significant difference between groups for length of hospital stay. Superficial wound breakdown is reduced by continuous subcuticular suturing. However, the trials that contributed to this result had suture removal in only one group (interrupted sutures), which may have led to this observation. The number of participants included in this review was small and follow-up after surgery was short. The overall quality of evidence was very low. Levels of bias across the studies were mostly high or unclear, so there may have been flaws in trial organisation that could produce erroneous results. Further well-designed trials at low risk of bias are necessary.
This review identified six studies (271 participants) comparing PGE1 with or without ACEi/ARB versus ACEi/ARB, no treatment or Xueshuantong (a Chinese medicinal herb). The results suggest that PGE1 may have a positive effect on DKD by reducing urinary albumin excretion rate (UAER), microalbuminuria and proteinuria. No serious adverse events or allergic responses were reported. All studies were methodologically poor and there is no strong evidence for recommending PGE1 for preventing the progression of DKD as a routine therapeutic measure. More high-quality research is needed.
This review found 100 studies that assessed the effect of higher versus lower intake of PUFAs in infants through searches of medical databases up to September 2015. However, only nine of these studies enrolling 2704 infants reported allergy outcomes (measures). Of these nine studies, we considered only one to be high quality. Five studies reported all allergy as an outcome measure; four studies reported asthma; all nine studies reported dermatitis/eczema; two studies reported allergic rhinitis and four studies reported food allergy. PUFA supplementation in infancy did not affect the risk of infant (aged up to two years of age) or childhood (aged up to 10 years of age) allergy, asthma, dermatitis/eczema and food allergy. There was a reduction in the risk of allergic rhinitis during infancy, however, there was no effect on the risk of childhood allergic rhinitis. There is insufficient evidence to determine an effect on allergic rhinitis. We graded the evidence for no effect on infant incidence, childhood incidence and childhood prevalence of all allergy as very low; the reduction in infant incidence of allergic rhinitis as very low; and the evidence for no effect on infant incidence, childhood incidence and childhood prevalence of all other allergic outcomes as very low to low. Further high quality studies are needed before we can determine an effect of higher PUFA intake in infants on the risk of allergic disease.
Warfarin is commonly prescribed to prevent blot clots in patients with medical conditions such as atrial fibrillation, heart valve replacement or previous blood clots. Warfarin is an effective treatment which has been used for many years but needs to be closely monitored, especially at the beginning of treatment, as there is a wide variation in response to dose. Monitoring of the response to dose is done using an International Normalized Ratio (INR) and it is important that patients remain within a narrow range (typically 2 to 3 INR) due to the need to balance the goal of preventing blood clots with the risk of causing excessive bleeding. This review included 12 randomised controlled trials comparing different warfarin doses given to patients beginning warfarin treatment. Most of the studies had a high risk of bias so the results were interpreted with caution. Those trials that were included compared loading doses in several different situations. The review authors divided the trials into four categories, 5 mg versus 10 mg initial doses (four studies), 5 mg versus other doses (two studies), 5 mg or 10 mg versus age adjusted doses (two studies), 5 mg or 10 mg versus genotype adjusted doses (four studies). The review authors concluded that there is still considerable uncertainty between the use of a 5 mg and a 10 mg loading dose for the initiation of warfarin. In the elderly, there is some evidence that lower initiation doses or age adjusted doses are more appropriate. However, there is insufficient evidence to warrant genotype adjusted dosing. We also found no data to suggest that any one method was safer than another.
We searched the medical literature up to May 2016 and found one randomised controlled trial (RCT) and one prospective cohort study to include in this review. These studies involved 493 participants in total. The RCT conducted at a dental hospital in the UK included 77 adolescent male and female participants, and the cohort study conducted at a private dental clinic in the USA involved 416 men aged 24 to 84 years. Available evidence is insufficient to show whether or not asymptomatic disease-free impacted wisdom teeth should be removed. One study at serious risk of bias provided very low quality evidence suggesting that the presence of asymptomatic disease-free impacted wisdom teeth is associated with increased risk of periodontitis (infection of the gums) affecting the adjacent second molar (teeth directly in front of the wisdom teeth) in the long term. In the same study, no evidence was found to suggest that the presence of asymptomatic disease-free impacted wisdom teeth increases the risk of caries affecting the adjacent second molar. Another study, also at high risk of bias, found no evidence to suggest that removal of asymptomatic disease-free impacted wisdom teeth has an effect on crowding in the dental arch. The included studies did not measure our primary outcome - health-related quality of life. Nor did they measure our secondary outcomes - costs, other adverse events associated with retention of asymptomatic disease-free impacted wisdom teeth (pericoronitis, root resorption, cyst formation, tumour formation, inflammation/infection) and adverse effects associated with their removal (alveolar osteitis/postoperative infection, nerve injury, damage to adjacent teeth during surgery, bleeding, osteonecrosis related to medication/radiotherapy, inflammation/infection). Evidence provided by the two studies included in this review is of low to very low quality, so we cannot rely on these findings. High-quality research is urgently needed to support clinical practice in this area. In light of the lack of available evidence, patient values should be considered and clinical expertise used when treatment decisions are made with patients who have asymptomatic disease-free impacted wisdom teeth. If the decision is made to retain asymptomatic disease-free impacted wisdom teeth, clinical assessment at regular intervals is advisable to prevent undesirable outcomes.
We included 32 studies involving a total of 748 participants aged above 18 with acute, postacute or chronic ischaemic or haemorrhagic stroke. The mean age in the experimental groups ranged from 43 years up to 70 years and from 45 years up to 75 years in the control groups. The level of participants' impairment ranged from severe to moderate. The majority of studies were conducted in an inpatient setting. Different stimulation types (anodal, cathodal, dual) of tDCS with different stimulation durations and dosages were administered and compared with sham tDCS or an active control intervention. Sham tDCS means that the stimulation is switched off covertly in the first minute of the intervention. This review found that tDCS might enhance ADLs, but it is still uncertain if arm and leg function, muscle strength and cognitive abilities may be improved. Proportions of adverse events and people discontinuing the treatment were comparable between groups. Included studies differed in terms of type, location and duration of stimulation, amount of current delivered, electrode size and positioning as well as type and location of stroke. Future research is needed in this area to foster the evidence base of these findings, especially regarding arm and leg function, muscle strength and cognitive abilities (including spatial neglect). The quality of evidence for tDCS for improving ADLs was very low to moderate. It was low for upper extremity function and low for adverse events and people discontinuing the treatment.
This review identified 13 studies (2032 participants). Methenamine hippurate may be effective in preventing UTI in patients without renal tract abnormalities particularly when used for short term prophylaxis. It does not appear to be effective for long term prophylaxis in patients who have neuropathic bladder. There were few adverse effects.Additional well controlled randomised controlled trials are necessary in particular to clarify effectiveness for longer term prophylaxis in those without neuropathic bladder.
This review analyzed the effects of furosemide on preterm babies receiving indomethacin to close the ductus arteriosus. The review of trials found not enough evidence to recommend routine use of furosemide in preterm infants who receive indomethacin for closing a ductus arteriosus.
Sixty-one studies presented data on 15,077 women with a wide range of risk factors for developing breast cancer, who underwent RRM. Risk-reducing mastectomy could include either surgically removing both breasts to prevent breast cancer (bilateral risk-reducing mastectomy or BRRM), or removing the disease-free breast in women who have had breast cancer in one breast to reduce the incidence of breast cancer in the other breast (contralateral risk-reducing mastectomy or CRRM). The evidence is current to July 2016. The BRRM studies reported that it reduced the incidence of breast cancer or the number of deaths or both, but many of the studies have methodological limitations. After BRRM, most women are satisfied with their decision, but reported less satisfaction with cosmetic results, body image, and sexual feelings. One of the complications of RRM was the need for additional unanticipated surgeries, particularly in women undergoing reconstruction after RRM. However, most women also experienced reduced worry of developing and dying from breast cancer along with diminished satisfaction with body image and sexual feelings In women who have had cancer in one breast, removing the other breast (CRRM) may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, carriers of mutations in the breast cancer genes, BRCA1 and BRCA2. CRRM was shown to reduce the incidence of contralateral breast cancer (CBC), but there is insufficient evidence that CRRM improves survival, and studies that control for multiple variables that can affect results are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Just over half of the studies were found to have a low risk of selection bias, that is, studies adjusting for systematic differences in prognosis or treatment responsiveness between the groups, and similarly, 60% had a low risk of detection bias, that is, studies considered systematic differences in the ways the outcomes were measured and detected. The primary cause for both selection bias and detection bias was not controlling for all major confounding factors, e.g., risk factors or having bilateral risk-reducing salpingo-oophorectomy (BRRSO - surgery to remove fallopian tubes and ovaries) in the subject and control groups. Performance bias (validation of the risk-reducing mastectomy) was not problematic, as most studies were based on surgical reports; three relied on self-reports and eight were unclear because of multiple sources of data and/or broad timeframe. Attrition bias was at high risk or unclear in approximately 13% of the studies. The mean or median follow-up period reported was from 1 - 22 years. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM.
In some studies, health professionals were simply given information about their performance and how this compared to professional standards or targets. In other studies, health professionals were also given a specific target that they personally were expected to reach, or were given an action plan with suggestions or advice about how to improve their performance. What happens when health professionals are given audit and feedback? The effect of using audit and feedback varied widely across the included studies. Overall, the review shows that: The effect of audit and feedback on professional behaviour and on patient outcomes ranges from little or no effect to a substantial effect. The quality of the evidence is moderate. Audit and feedback may be most effective when: 1. the health professionals are not performing well to start out with; 2. the person responsible for the audit and feedback is a supervisor or colleague; 3. it is provided more than once; 4. it is given both verbally and in writing; 5. it includes clear targets and an action plan. In addition, the effect of audit and feedback may be influenced by the type of behaviour it is targeting. It is uncertain whether audit and feedback is more effective when combined with other interventions.
We included 425 research reports described in 551 articles, which had studied the subsequent full publication of 307,028 abstracts from a variety of biomedical and social sciences. Fifty-four reports included data from abstracts describing randomized or controlled trials. Of the 425 reports, 376 were published in English, and 49 in other languages. 1. Less than half of all studies, and about two-thirds of randomized trials, initially presented as summaries or abstracts at meetings, are published as journal articles in the 10 years after presentation. 2. Studies with positive results are more likely to be published. 3. Studies with larger sample sizes are more likely to be published. 4. Studies with abstracts presented orally are more likely to be published than those presented as posters. 5. Studies accepted for presentation at a meeting are more likely to be published than those not accepted. 6. Studies describing basic science are more likely to be published that those describing clinical research. 7. Studies describing randomized trials are more likely to be published than those describing other types of studies. 8. Studies that took place in multiple centers are more likely to be published than those at a single center. 9. Studies classified as ‘high quality’ are more likely to be published than ‘low quality’ studies. 10. Studies with authors from an academic setting are more likely to be published than those with authors from other settings. 11. Studies considered by the report authors to have a high impact are more likely to be published than other studies. 12. Studies with funding source reported are more likely to be published than those not reporting funding. 13. Studies originating in North America or Europe are more likely to be published than those originating elsewhere. 14. Studies from English-speaking countries are more likely to be published than studies originating elsewhere. We have confidence in our findings. We considered five criteria to constitute a risk of bias in the included reports, including methods to identify and match full publications to abstracts, and methods to determine whether a factor was associated with full publication. Overall, 7.5% (32/425) of the reports were scored as having an overall high risk of bias, 83.1% (353/425) had at least one criterion at high risk of bias, and 6.1% (26/425) had all criteria at low risk of bias. Our search updated our 2007 review and is current to February 2016. After the considerable work involved in including more than 300 additional studies from the February 2016 searches, we chose not to update the search again because additional searches are unlikely to change our overall conclusions in any important way.
We found one eligible study of 55 participants from the UK. All participants in the study had a history of contact lens wear. The study randomly assigned people with AK to one of two medical treatment options: chlorhexidine eye drops or polyhexamethylene biguanide (PHMB) eye drops. Participants in the study were treated for 51 to 145 days. In the one study identified, similar results were seen between the chlorhexidine and PHMB groups in terms of resolution of infection, changes in vision, or need for surgery. However, the number of participants in the study was small and the results uncertain; thus, we cannot be confident that there are really no differences between these treatments. No serious side effect was observed with either treatment in the study. Although the study was well-designed with no suggestion of bias, the results must be interpreted carefully because of the small number of participants.
In May 2017 we searched for all clinical trials that investigated the effectiveness of trihexyphenidyl for people with dystonic cerebral palsy. We included one Australian trial that involved 16 children (10 boys, 6 girls) with cerebral palsy and dystonia. They had an average age of nine years. The children were divided into two different groups. Both groups took 12 weeks of trihexyphenidyl and 12 weeks of a placebo (something that looks the same as trihexyphenidyl but with no active ingredient), with a 4-week break in between during which they received neither. The only difference between the groups was that one group started with trihexyphenidyl and then had placebo, and the other group started with placebo and then had trihexyphenidyl. We found no evidence that trihexyphenidyl was effective for reducing dystonia or improving upper arm function in children with cerebral palsy and dystonia. Trihexyphenidyl may be associated with an increased risk of side effects (agitation, constipation, dry mouth and poor sleep). There was some evidence that trihexyphenidyl may improve individual goals set by the child and family around improved participation in activities of daily living. The study did not measure pain or quality of life. We rated the quality of the evidence as low because the one study included a small number of children and there are no other studies to support the findings. Therefore, we are uncertain about the effectiveness of trihexyphenidyl in reducing dystonia or improving arm function and participation in everyday activities of people with cerebral palsy and dystonia.
This review of trials found that using mechanical devices might be better than no treatment but the evidence is weak. There was not enough evidence to recommend any specific type of device or to show whether mechanical devices are better than other forms of treatment such as pelvic floor muscle training.
We included four studies with a total of 152 adult participants. These studies were conducted in several countries (Norway, the United Kingdom and Canada). All of them compared debridement to no debridement after endoscopic sinus surgery. The minimum follow-up time in the studies ranged from 3 to 12 months. Only one study reported health-related quality of life scores and only one reported disease severity scores. However, all four studies reported scores for the appearance of the sinonasal cavities viewed through an endoscope. Adverse effects of this procedure and rates of revision surgery were not reported in any of these studies. Health-related quality of life and disease severity scores were not significantly different between those patients who underwent debridement and those who did not. All four studies demonstrated better post-surgical endoscopic appearance in the debridement group, although the size of improvement was not statistically significant. A lower rate of intranasal scarring was noted in the patient group that underwent debridement. Nonetheless, the overall evidence for all of these outcomes is of low quality. We identified several problems or potential problems in these studies. The most important was that in each study a different protocol was used for the number of debridement interventions performed per patient and the time interval between each such intervention. In addition, the numbers of patients in the study groups were relatively small. We therefore determined the overall quality of the evidence to be low for all outcomes. The evidence in this review is up to date to May 2018.
This review included 19 studies involving over 310,000 women. Seven trials were conducted in Africa, six in Indonesia, two in Bangladesh, and one each in Nepal, China, India, UK and USA. Most of the trials were conducted in populations considered to be vitamin A deficient (except USA and UK). The overall risk of bias was low to unclear in most of the trials, and the body of evidence was moderate to high quality. The findings indicate that routine supplementation with vitamin A (either alone or in combination with other supplements) during pregnancy did not reduce mother or newborn baby deaths. There is good evidence that antenatal vitamin A supplementation does reduce maternal anaemia in women who live in areas where vitamin A deficiency is common or who are HIV-positive. The trials published so far did not report any side effects or adverse events. The available evidence suggests a reduction in maternal infection but these data are not of a high quality and further trials would be needed to confirm or refute this. Taking vitamin A supplements during pregnancy does not help to prevent maternal deaths (related to pregnancy) or perinatal or newborn baby deaths. Taking vitamin A supplements during pregnancy does not help to prevent other problems that can occur such as stillbirth, preterm birth, low birthweight of babies or newborn babies with anaemia. However, the risk of maternal anaemia, maternal infection and maternal night blindness is reduced.
In January 2016, we found seven studies that assessed liposomal bupivacaine nerve block. Three studies were listed as completed but had not reported results. This left four studies involving 299 participants for this review. Two studies investigated liposomal bupivacaine given between two of the layers of abdominal muscles to block the nerves supplying sensation to that area (known as a transversus abdominus plane (TAP) block); one study investigated liposomal bupivacaine given around the nerves that supply sensation to the penis (dorsal penile nerve block); and one study investigated the ankle (ankle block). We did not identify any studies that reported our primary outcome cumulative pain score between 0 and 72 hours or pain-centred secondary outcomes. Two studies reported cumulative opioid (a strong painkiller) use with inconsistent results. We looked for results about side effects but none were reported, however no participants dropped out of the studies due to side effects. Overall, the lack of evidence, due to the small number of trials each reporting different outcomes, prevented a full assessment of the role of liposomal bupivacaine administered as a nerve block for the management of pain after surgery in adults. Due to the small number of trials, and small number of participants in these trials, the quality of evidence was very low. As such, further research is required to evaluate the role of liposomal bupivacaine as a nerve block to treat pain after surgery.
We have found two trials comparing these devices and including 67 participants in total. The studies compared different devices, so we could not pool the information from the two studies. However, one study showed that long intravenous lines last for longer than short intravenous lines (thus reducing the number of procedures which a participant has to undergo for a course of antibiotics). Patient satisfaction was higher with long intravenous lines compared to short intravenous lines. The study comparing two different types of long intravenous line did not show that one type was clearly better than another. Neither study was large enough to show differences in complications for the different devices. Neither study reported on important outcomes, such as the number of attempts required to insert the device. We recommend further research to compare different types of percutaneous long intravenous line.
We identified seven trials with a combined total of 542 participants comparing percutaneous transluminal angioplasty (PTA) alone versus PTA with stent placement (current until June 2018). One trial randomised limbs to PTA alone or PTA with stent placement, and the remaining studies randomised participants. Full analysis of five trials shows that the technical success rate of re-opening the narrowed artery was higher in the stent group than in the PTA group. However, we noted no clear differences in patency (opened vessel remaining open) of the treated vessel at six months. The complication rate of the procedure, the number of major amputations at 12 months, and the number of deaths at 12 months also did not differ greatly between treatment groups. The overall certainty of evidence provided by the trials included in this review was moderate. Trials differed in their methods. Two studies reported poorly on the methods used to generate random numbers and to allocate participants to different groups. All studies were unblinded. All included studies were rated as direct in their relevance to the review question. Overall, we downgraded the certainty of evidence for all outcomes by one level to moderate due to inconsistency of results across studies and the small numbers of studies and participants. PTA with stent placement is better than PTA alone for restoring vessel patency immediately; however we found no clear difference in short-term patency at six months between the two groups. Trials show no clear differences between groups in complications at or around the time of the procedure, major amputation, and death. Currently available data suggest that high-certainty evidence is insufficient to show that PTA with stent placement is superior to PTA alone for treatment of infrapopliteal arterial lesions. Further studies should standardise the use of blood-thinning drugs (antiplatelets/anticoagulants) before and after both interventions to improve the comparability of the two treatments.
The evidence is current to 7 July 2015. Our review identified nine clinical trials that compared the effectiveness and safety of fulvestrant against other standard treatments for advanced hormone-sensitive breast cancer and pooled the data from these trials to analyse all the data together. Three different endocrine therapies were analysed as comparator drugs against fulvestrant. Two of these drugs were the aromatase inhibitors anastrozole and exemestane, which lower oestrogen levels in postmenopausal women, and the third was tamoxifen, which works by blocking oestrogen. Four of the studies were in the first-line setting, meaning that fulvestrant was tested against these endocrine therapies as the initial treatment for advanced disease. Five of the studies tested fulvestrant in the second-line or more setting, meaning after the women had progressed on a prior initial treatment for advanced disease. Two studies examined fulvestrant in combination with anastrozole against anastrozole alone, and the other seven studies compared fulvestrant alone with other comparator drugs. We found that fulvestrant was at least as effective as the other three standard endocrine therapies used in the treatment of advanced hormone-sensitive breast cancer and is possibly more effective at the new standard dose of 500 mg, rather than the lower dose of 250 mg, which was previously used and tested in all but one of the included studies. We also found that combining fulvestrant with an aromatase inhibitor did not improve effectiveness, and neither was effectiveness influenced by whether fulvestrant was used as the first treatment upon diagnosis of advanced disease or after another endocrine therapy. This was evident in the pooled data analysis for both survival time without progression of cancer and the rate of tumour shrinkage or stabilisation due to fulvestrant as compared with the other endocrine therapies. In addition, fulvestrant-treated women did not experience worse side effects than those receiving the comparator endocrine therapies, and quality of life was equivalent in both fulvestrant-treated women and women treated with the other endocrine therapies. Fulvestrant can therefore be considered an effective and safe treatment for postmenopausal women with advanced hormone-sensitive breast cancer, when treatment with endocrine therapy is indicated. All studies were of high quality.
Seven small studies of variable quality were reviewed. The studies tested the effect of maintenance treatment with probiotics (e.g. Lactobacilli GG, Escherichia coli strain Nissle 1917, VSL#3, Saccharomyces boulardii) among patients with Crohn's disease in remission. Remission was induced by medical or surgical treatment. The studies lasted for 6 months to a year. The studies did not demonstrate any benefit for probiotic treatment. Probiotics were generally well tolerated and few side effects were reported. Reported side effects include bloating, diarrhoea, constipation, nausea and epigastric pain. Currently, there is no evidence to support the use of probiotics for the maintenance treatment of Crohn's disease. It is possible that larger studies might show that this approach to treatment is effective.
This review included three trials that randomly assigned 175 women with the placenta remaining undelivered more than 15 minutes after delivery to either a placebo or the tocolytic nitroglycerin. Both groups received oxytocin to stimulate contractions of the uterus. Combined administration of nitroglycerin and oxytocin did not reduce the need for manual removal of placenta, blood loss, nor the incidence of severe postpartum haemorrhage. Nitroglycerin administration did not cause headache but resulted in a mild drop in blood pressure and a related increase in heart rate. Two out of the three trials had low risk of bias but this result needs confirmation in larger trials with adequate sample sizes to verify the role of nitroglycerin and other tocolytic drugs in managing different subtypes of retained placenta. The trials in this review did not specify the type of retained placenta. We have included an explanation of some of the scientific terms that are used in this review in a glossary (see Appendix 1).
Twelve randomised clinical trials fulfilled the inclusion criteria of this review. Primary analysis of the data based on criteria described beforehand (intention-to-treat model assigning unfavourable outcome for missing data) showed that hepatitis B vaccination has an unclear effect on the risk of developing hepatitis B infection. Analysis of data of available participants in the various trials showed that as compared to not vaccinating, hepatitis B vaccination reduces the risk of developing hepatitis B infection; by 88% for hepatitis B surface antigen marker and 62% for anti-core antibody marker. One should note, that these findings are based on only four randomised clinical trials of poor methodological quality involving 1230 participants. When compared with other vaccines or placebo, hepatitis B vaccination results in comparable risk of developing adverse events. This includes serious adverse events such as admission to hospital and convulsions, as well as less serious events such as fever, local redness, and pain. This shows that the risk of developing these adverse events is not more than with other vaccinations. There was not enough data to draw definite conclusions on the effect of hepatitis B vaccination on compliance and cost-effectiveness.
We systematically reviewed ten studies assessing the efficacy of antidepressants, for a total of 885 participants. The evidence is current to 3 July 2017. Due to the small number of people in the studies, and issues with how the studies reported what was done, there is uncertainty over whether antidepressants were better than placebo in terms of depressive symptoms after 6 to 12 weeks of treatment. We did not have enough evidence to determine how well antidepressants were tolerated in comparison with placebo. Our results did not show whether any particular antidepressant was better than any other in terms of both beneficial and harmful effects. To better inform clinical practice, we need large studies which randomly assign people to different treatments. Currently, we cannot draw reliable conclusions about the effects of antidepressants on depression in people with cancer. The certainty of the evidence was very low because of a lack of information about how the studies were designed, low numbers of people in the analysis of results, and differences between the characteristics of the studies and their results. Despite the impact of depression on people with cancer, the available studies were very few and of low quality. This review found very low certainty evidence for the effects of these drugs compared with placebo.
The aim of this review was to determine if these interventions are effective in the management of conduct disorder and delinquency in children and adolescents, aged 10-17. Current evidence suggests that family and parenting interventions for juvenile delinquents and their families have beneficial effects on reducing time spent in institutions. This has an obvious benefit to the participant and their family and may result in a cost saving for society. These interventions may also reduce rates of later arrest, but at present these results need to be interpreted with caution, because of diversity in the results of studies.
Studies included in this review are current to March 2016. We included 10 studies involving 545 participants for evaluation of the diagnostic accuracy of ultrasound for confirmation of gastric tube placement. Most studies showed good performance for correct placement of the tube. However, few data were available for incorrect placement of the tube and the possible complications of a misplaced tube. Among the included studies, only 43 participants had a misplaced tube. None of the studies reported complications during ultrasound use. Three methods of ultrasound were reported: neck approach, upper abdominal (tummy) approach and a combination of both. No included studies indicated that ultrasound had sufficient accuracy as a single test for the confirmation of gastric tube placement for feeding. In contrast, ultrasound combined with other tests (e.g. saline flush visualization (pushing salt solution through the tube and seeing it inside the stomach by ultrasound)) might be useful for the confirmation of tubes used for gastric drainage. Generally, the studies were of low or unclear methodological quality. We considered only three (30%) of the 10 included studies to be representative of patients in practice because they performed ultrasound after they confirmed correct position by other methods. The studies reported a variety of results for incorrect tube placement. Larger studies are needed to investigate whether ultrasound could replace X-rays for confirming gastric tube placement, as well as whether ultrasound could decrease severe complications, such as pneumonia, from a misplaced tube.
Cochrane authors performed a comprehensive literature search of the standard medical databases to 8 April 2019 in consultation with the Cochrane Gynaecology and Fertility Group Information Specialist, for randomised clinical trials (RCTs: clinical studies where people are randomly put into one of two or more treatment groups) investigating the effect of thyroid hormones (levothyroxine) for women diagnosed with ATD or mildly underactive thyroid who were planning to undergo assisted reproduction. Two authors independently selected studies, evaluated them, extracted data and attempted to contact the authors where data were missing. We found four RCTs (with 820 women) that met our inclusion requirements. The thyroid hormones were administered in a range of doses to women diagnosed with mildly underactive thyroid or presence of thyroid antibodies (ATD). In women with mild thyroid hormone imbalance and unknown thyroid autoimmunity status, we were uncertain whether thyroxine replacement had an effect on live birth or miscarriage rates (very low-quality evidence from one study involving 70 women). In women with mildly underactive thyroids (with or without ATD), the evidence suggested that thyroxine replacement may have improved live birth rates (low-quality evidence from one study involving 64 women) and it may have led to similar miscarriage rates (low-quality evidence from one study involving 64 women). The evidence suggested that women with mildly underactive thyroid (with or without ATD) would have a 25% chance of a live birth with placebo or no treatment, and 27% to 100% with thyroxine. In women with ATD and normal thyroid function, treatment with thyroxine replacement compared with placebo or no treatment may have led to similar live birth rates (low-quality evidence from two studies involving 686 women) and miscarriage rates (low quality evidence from two studies involving 686 women). The evidence suggested that women with ATD and normal thyroid function would have a 31% chance of a live birth with placebo or no treatment, and 26% to 40% with thyroxine. Side effects were rarely reported. One study reported none out of 32 preterm births in the thyroxine replacement group and one out of 32 preterm births in the control group in women diagnosed with mildly underactive thyroid (with or without ATD). One study reported 21 out of 300 preterm births in the thyroxine replacement group and 19 out of 300 preterm births in the control group in women diagnosed with ATD and normal thyroid function. None of the studies reported on other maternal pregnancy complications, foetal complications or side effects of thyroxine. The evidence was of very low to low quality. We downgraded the evidence as it was based on single, small trials with widely variable results.
We only found one reasonably good but small trial. It did not show that compliance therapy really effected compliance with medication, psychotic symptoms, or quality of life but it was always too small really to show this for certain. The study did, however, suggest that the compliance therapy may help people spend shorter times in hospital across a two year period, when compared with standard care. There is a need for more studies and we have proposed a design that could be conducted within the confines of routine care for outcomes of interest to everyone involved.
This review included one low quality trial of a specialist nurse counselling intervention compared with routine outpatient clinic follow up. No data were reported on remission outcomes. Counselling by a specialist nurse might improve mental health related quality of life for some IBD patients in the short term. However, the poor quality of the one included study does not allow for any definitive conclusions regarding the impact of the nurse-led counselling program. Better designed studies are needed to assess the impact of specialist nursing interventions on the care and management of patients with inflammatory bowel disease.
Researchers and organizations often use evidence from randomized controlled trials (RCTs) to determine the efficacy of a treatment or intervention under ideal conditions, while studies of observational designs are used to measure the effectiveness of an intervention in non-experimental, 'real world' scenarios. Sometimes, the results of RCTs and observational studies addressing the same question may have different results. This review explores the questions of whether these differences in results are related to the study design itself, or other study characteristics. This review summarizes the results of methodological reviews that compare the outcomes of observational studies with randomized trials addressing the same question, as well as methodological reviews that compare the outcomes of different types of observational studies. The main objectives of the review are to assess the impact of study design--to include RCTs versus observational study designs (e.g. cohort versus case-control designs) on the effect measures estimated, and to explore methodological variables that might explain any differences. We searched multiple electronic databases and reference lists of relevant articles to identify systematic reviews that were designed as methodological reviews to compare quantitative effect size estimates measuring efficacy or effectiveness of interventions of trials with observational studies or different designs of observational studies. We assessed the risks of bias of the included reviews. Our results provide little evidence for significant effect estimate differences between observational studies and RCTs, regardless of specific observational study design, heterogeneity, inclusion of pharmacological studies, or use of propensity score adjustment. Factors other than study design per se need to be considered when exploring reasons for a lack of agreement between results of RCTs and observational studies.
In one trial involving 200 women, uterine massage was given every 10 minutes for 60 minutes after delivery of the placenta effectively reduced blood loss, and the need for additional uterotonics, by some 80%. The numbers of women losing more than 500 mL of blood were too small for meaningful comparison. Two women in the control group and none in the uterine massage group needed blood transfusions. The second trial involved 1964 women who were assigned to receive oxytocin, uterine massage or both after delivery of the baby and before delivery of the placenta. There was no added benefit for uterine massage when oxytocin was used. The results of this review are inconclusive. The methodological quality of the two included trials was high but it is possible that there were differences in the procedures used in the study sites. Disadvantages of uterine massage include the use of staff time, and discomfort caused to women. The findings should not change the recommended practice. It is likely that any reduction in blood loss was limited with the use of oxytocin in these trials. Uterine massage may also have increased apparent blood loss by pressing pooled blood out from the uterine cavity. There is a need for more trials, especially in settings where uterotonics are not available. Uterine massage could be a simple inexpensive intervention if proved effective.
This review assessed the analgesic efficacy and adverse effects that single dose oral dextropropoxyphene taken alone or in combination with paracetamol had in treating moderate to severe postoperative pain. The combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to that of tramadol 100 mg for single dose studies in postoperative pain but with a lower incidence of side effects. This review also highlighted that Ibuprofen 400 mg was yet more effective than both tramadol 100 mg and dextropropoxyphene 65 mg.
Our review included 11 clinical trials that randomized 1838 participants (current until December 2015). The trials included thigh and leg arteries above and below the knee. The trials were carried out in Europe and the USA, and all used DEBs that contained paclitaxel. Four companies manufactured the DEB devices: Bard, Bavaria Medizin, Biotronik, and Medtronic. Most participants were followed for 12 or more months (called follow-up). At six and 12 months of follow-up, DEBs were associated with improved primary vessel patency, which is an indicator of whether a vessel is still patent without any further interventions (blood flowing well), late lumen loss, which is the difference in millimeters between the angioplastied segment and how narrow it is on follow-up, target lesion revascularization, which is an indicator of whether a person received more than one treatment to the same artery during the period covered by the study, and binary restenosis, which occurs when a treated artery becomes narrowed again after being previously treated. Unfortunately, early anatomic (structural) advantages of DEBs were not accompanied by improvements in quality of life, functional walking ability, or in the occurrence of amputation or death. When we specifically examined arteries below the knee and people who had very advanced PAD, we found no clinical or angiographic advantage for DEBs at 12 months of follow-up compared with uncoated balloon angioplasty. In summary, DEBs have several anatomic advantages over uncoated balloons for the treatment of lower limb PAD for up to 12 months after undergoing the procedure. However, more data are needed to assess the long-term results of this treatment option adequately. All the trials had differences in the way in which they inserted the balloons, and in the type and duration of additional antiplatelet (anticlotting) therapy, leading to downgrading of the quality of the evidence. The quality of the evidence presented was moderate for target lesion revascularization and change in Rutherford category (a way of classifying PAD), and high for amputation, primary vessel patency, binary restenosis, death, and change in ankle-brachial index (which is used to predict the severity of PAD).
These conclusions are based on 24 randomised controlled trials with 6915 participants who were treated as outpatients in all but one trial that involved adolescent inpatients. The majority of participants were men, median age 42 years. Most studies were conducted in Europe; two studies were conducted in the United States and one study in each of South Korea,Australia and Brazil. The effects of acamprosate did not differ in industry-sponsored and non-profit funded trials. Three trials compared acamprosate and naltrexone and did not indicate a superiority of one or the other drug on return to any drinking, return to heavy drinking and cumulative abstinence duration.
We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a varied set of observations: participant people and observations on participants and countries (the object of some studies). Any total figure would therefore be misleading. Respiratory virus spread can be reduced by hygienic measures (such as handwashing), especially around younger children. Frequent handwashing can also reduce transmission from children to other household members. Implementing barriers to transmission, such as isolation, and hygienic measures (wearing masks, gloves and gowns) can be effective in containing respiratory virus epidemics or in hospital wards. We found no evidence that the more expensive, irritating and uncomfortable N95 respirators were superior to simple surgical masks. It is unclear if adding virucidals or antiseptics to normal handwashing with soap is more effective. There is insufficient evidence to support screening at entry ports and social distancing (spatial separation of at least one metre between those infected and those non-infected) as a method to reduce spread during epidemics.
We included 23 studies that compared the effectiveness of combined treatment with beta-agonists and anticholinergics versus treatment with beta-agonists alone. A total of 2724 adult participants were enrolled in the studies. Salbutamol (also called albuterol) was the most common beta-agonist investigated and ipratropium bromide was the most common anticholinergic assessed. We found that most studies did not report sources of funding (14 studies); one study was supported by a hospital; another received support from a pharmaceutical company, but indicated that there was no involvement from the company in conducting or reporting research. Two studies were part-funded and four were funded by pharmaceutical companies. Patients with severe asthma who received combined treatment of beta-agonists and anticholinergics were less likely to be admitted to hospital. An estimated 65 fewer patients per 1000 would require hospital admission after receiving combined inhaled therapy in the emergency department. Among patients with mild -to-moderate asthma, combined inhaled therapy was less effective in preventing admission to hospital compared with people with severe asthma. Patients receiving combined treatment were less likely to return to the emergency department with worsening asthma symptoms and had better outcomes in most lung function tests. On the other hand, 103 more participants per 1000 who receive combined inhaled therapy would experience side effects compared to people who receive beta-agonists alone. Quality of the evidence that combination inhaled therapy can improve health outcomes compared to treatment with beta-agonists alone ranged from very low to moderate. Our confidence about the effects of combination inhaled therapy on hospital admissions, peak expiratory flow, percent change in peak expiratory flow from baseline, and relapse was moderate because of the overall risk of bias among included studies. Factors associated with inconsistency and imprecision were additional aspects that reduced the quality of the evidence for forced expiratory volume in one second, and percent predicted peak expiratory flow.
This review includes 53 randomized trials with a total of 8548 participants. Oral 5-ASA was found to be more effective than placebo (fake drug). Although oral 5-ASA drugs are effective for treating active ulcerative colitis, they are no more effective than SASP therapy. Patients taking 5-ASA are less likely to experience side effects than patients taking SASP. Side effects associated with 5-ASA are generally mild in nature, and common side effects include gastrointestinal symptoms (e.g. flatulence, abdominal pain, nausea, and diarrhea), headache and worsening ulcerative colitis. Male infertility is associated with SASP and not with 5-ASA, so 5-ASA may be preferred for patients concerned about fertility. 5-ASA compounds are more expensive than SASP, so SASP may be the preferred option where cost is an important factor. 5-ASA dosed once daily appears to be as effective and safe as conventionally dosed (two or three times daily) 5-ASA. There do not appear to be any differences in effectiveness or safety among the various 5-ASA formulations. A daily dosage of 2.4 g appears to be a safe and effective therapy for patients with mild to moderately active ulcerative colitis. Patients with moderate disease may benefit from an initial dose of 4.8 g/day.
We examined research published up to 14 February 2017. We looked for studies of boys and girls from age one to 18 years who sometime before had problems with kidney stones and who were assigned to a different diet or a medicine (or both) to stop the stones from coming back for at least 12 months. We were most interested in whether the stones returned, how many side effects there were and if children had to have more treatments for kidney stones. We only found one small study with 125 children (72 boys and 53 girls) who had been treated with waves similar to those that carry sound, so-called shock waves to treat their kidney stones. These children formed kidney stones for unknown reasons and had otherwise normal kidneys. Fifty-two children had no more stones and 44 children still had small stone pieces left when they started the study. One group was given a medicine by mouth called potassium citrate; the other group was given no special medicine. The children were on this study for about two years. The study reported on the findings in 96 children; 48 in each group. Based on this study, we found that this medicine may result in stones coming back less often. However, we are not sure about this finding because the study was not of good quality and small. One in eight patients stopped the medicine because of side effects. We did not find any information on how often children had to be treated for stones again. The evidence quality for stones coming back less often was low and that for side effects very low. We found no evidence on how often children had to be treated for stones again.
We found four studies that included a total of 690 adults who had been in the ICU. Patients were randomized to receive exercises and assistance to move early in their stay in the ICU or to usual care. All participants had been on a breathing machine at some point during their time in the ICU. Three studies included adults with critical illness involving severe disease of the lungs or severe body response to infection and one study involved adults who had undergone cardiac surgery. One study was funded by the Intensive Care Foundation, Royal Brisbane and Women's Hospital, Australia and the investigator was supported by a Postgraduate Award from Singapore. We were unable to determine whether early movement or exercise of critically ill people in the ICU improves their ability to do daily activities, muscle strength, or quality of life. There were mixed results on the effect of early movement or exercise on physical function. One study found that on some measures of physical function, participants who received the intervention could get out of bed earlier and walk greater distances. However, the same study found no differences in the number of daily activities they could do when leaving ICU. Early movement or exercise appears safe as the number of adverse events was very low. There was no difference between groups in time spent in hospital, muscle strength or death rates. Overall there was low-quality evidence from these studies. The main reasons were that only a small number of studies have examined this intervention. Most studies included only a small number of participants, and participants and study staff were aware of group assignment. In addition, in two studies, staff assessing outcomes were aware of group assignment. There were also differences in participant diagnoses, interventions and the way that outcomes were measured. The four studies awaiting classification, and the three ongoing studies may alter the conclusions of the review once these results are available. Evidence in this review is current to August 2017.
This review included nine randomised controlled trials involving 1118 women and assessed six of these studies (involving 394 women) comparing umbilical vein injection of normal saline with or without oxytocin. Other comparisons did not provide the required information. With umbilical vein injection of saline solution plus oxytocin versus umbilical vein injection of saline solution there was no evidence of a difference in the amount of blood lost, duration of the third stage of labour or need for manual removal of a retained placenta. routine use of umbilical injection after childbirth to deliver any infusion, though the combined results of the small number of relevant studies showed no evidence of effect and further research is needed to make a conclusion. There is a need for training in the technique and a possible higher cost of materials.
This review assesses data from randomised trials of the three classes of drugs commonly used as add-on (adjuvant) treatment to levodopa therapy in people with PD who have motor complications. Forty-four randomised trials, involving 8436 participants were identified as suitable for this review. The review confirms reports from individual trials that, compared to placebo, add-on therapy (on a background of levodopa) significantly reduces patient off-time, reduces the required levodopa dose and improves overall disability scores (measured on the Unified Parkinson's Disease Rating Scale - UPDRS). However, dyskinesia and other side-effects such as constipation, hallucinations and vomiting are increased with adjuvant therapy. Indirect comparisons of the three drug classes (dopamine agonists, COMTIs and MAOBIs) suggest that dopamine agonists may provide more effective symptomatic control than COMTI and MAOBI therapy. COMTI and MAOBI have comparable efficacy. There was no significant evidence of differences in efficacy between individual drugs within the drug classes, other than tolcapone appearing more effective than entacapone. However these observations are based on indirect comparisons between trials, so could be due to other factors, e.g. differences in the types of people included in the trials, and so should to be interpreted with caution. This review highlights the need for large randomised studies that directly compare the different drug classes with patient-rated overall quality of life and health economic measures as the primary outcomes.
Glutamine is a non-essential amino acid which is abundant in the healthy human body. There are studies reporting that muscle and plasma glutamine levels are reduced in patients with critical illness, or following major surgery, suggesting that the body's demand for glutamine is increased in these situations. In the past decade, several clinical trials have examined the effects of glutamine supplementation in patients with critical illness or receiving surgery, and a systematic review of this clinical evidence suggested that giving glutamine to these patients may reduce infection and mortality rates. However, two recent large-scale clinical trials, published in 2011 and 2013, did not find any beneficial effects of glutamine supplementation in patients with critical illness. In this review, we searched the available literature until May 2013 and included studies which compared the outcomes with glutamine supplementation and without in adults with a critical illness or undergoing elective major surgery. We included 57 articles from 53 randomized controlled studies in this review. These 53 studies enrolled a total of 4671 patients with critical illness or undergoing elective major surgery. The risk of mortality, length of intensive care unit stay and the incidence of side effects were not significantly different between those given glutamine and those who were not. However, our findings showed that the risk of infectious complications in patients who were given glutamine was 79% of the risk for those who were not. In other words, 12 patients need to be supplemented with glutamine to prevent one case of infection. This result needs to be interpreted cautiously as the quality of evidence for infectious complications was moderate. The funnel plot for this outcome suggested that smaller studies with outcomes favouring non-supplemented patients have not been published, and further research is likely to have an impact on the estimate of effect for this outcome. The findings from this review also suggested that the average length of hospital stay in critically ill or surgical patients supplemented with glutamine was 3.46 days shorter than for patients without glutamine supplementation. This result should also be treated with care as there was substantial heterogeneity between these studies. We found in this review that the mean number of days on mechanical ventilation was 0.69 days shorter in patients with glutamine supplementation than for patients without glutamine supplementation.
This review found 15 randomised studies that compared HFNC with other non-invasive ways of supporting babies' breathing. The studies differed in the interventions that were compared, the gas flows used and the reasons for respiratory support. When HFNC was used as first-line respiratory support after birth compared to CPAP (4 studies, 439 infants), there were no differences in the rates of death or chronic lung disease (CLD). HFNC use resulted in longer duration of respiratory support, but there were no differences in other outcomes. One study (75 infants) showed no differences between HFNC and NIPPV as breathing support after birth. When HFNC were used after a period of mechanical ventilation (total 6 studies, 934 infants), there were no differences between HFNC and CPAP in the rates of death or CLD. There was no difference in the rate of treatment failure or reintubation. Infants randomised to HFNC had less trauma to the infant's nose. There was a small reduction in the rate of pneumothorax in infants treated with HFNC. We found no difference between the effect of HFNC compared with CPAP in preterm infants in different gestational age subgroups, though there were only small numbers of extremely preterm and late preterm infants. One trial (28 infants) found similar rates of reintubation for humidified and non-humidified HFNC, and two other trials (100 infants) found no difference between different models of equipment used to deliver humidified HFNC. For infants weaning from non-invasive respiratory support (CPAP), two studies (149 infants) found that preterm infants randomised to HFNC had a reduced duration of hospitalisation compared with infants who remained on CPAP. HFNC use has similar rates of efficacy to other forms of non-invasive respiratory support in preterm infants for preventing treatment failure, death and CLD. Most evidence is available for the use of HFNC as post-extubation support. Following extubation, use of HFNC is associated with less nasal trauma, and may be associated with reduced pneumothorax compared with nasal CPAP. Further adequately powered randomised controlled trials should be undertaken in preterm infants comparing HFNC with other forms of primary non-invasive support after birth and for weaning from non-invasive support. Further evidence is also required for evaluating the safety and efficacy of HFNC in extremely preterm and mildly preterm subgroups, and for comparing different HFNC devices.
Evidence from poor quality, small trials, suggests that superficial and partial thickness burns heal more quickly with silicon-coated nylon, silver containing dressings and biosynthetic dressings than with silver sulphadiazine cream. Burns treated with hydrogel dressings healed more quickly than those treated with usual care.
Exercise is moderately more effective than no therapy for reducing symptoms of depression. Exercise is no more effective than antidepressants for reducing symptoms of depression, although this conclusion is based on a small number of studies.  Exercise is no more effective than psychological therapies for reducing symptoms of depression, although this conclusion is based on small number of studies. The reviewers also note that when only high-quality studies were included, the difference between exercise and no therapy is less conclusive. Attendance rates for exercise treatments ranged from 50% to 100%. The evidence about whether exercise for depression improves quality of life is inconclusive. The reviewers recommend that future research should look in more detail at what types of exercise could most benefit people with depression, and the number and duration of sessions which are of most benefit. Further larger trials are needed to find out whether exercise is as effective as antidepressants or psychological treatments.
We included nine studies in this review which involved 134 participants with TBI. Only five studies, including 105 people provided usable results. These studies tested the effects of a range of treatments, including medicines (baclofen or botulinum toxin A), casting, physiotherapy, splints, a table that moves people from the lying position to standing and electrical stimulation (where electrical impulses are delivered to the muscles). Studies inadequately reporting results had tested the effect of medicines (baclofen or tizanidine). Of the five studies with results, three were funded by governments, charities or health services and two were funded by a drug manufacturer and medical technology company. The other four studies without useable results were funded by drug manufacturer or medical technology companies. This evidence is current to June 2017. Interpreting the results of the studies was difficult because of a lack of information and concerns about the quality of the evidence. For spasticity, some studies concluded that the treatment they tested made an improvement, and others found no difference between treatments. The most common side effect was minor skin damage in people who received casting. We believe it would be misleading to provide any further description of study results given the quality of the evidence was very low for all measurements. The quality of this evidence was very low; we only had five studies with results and none of the studies were large or comparable with one another. We also had concerns about how they were conducted or analysed. Because of this, we cannot draw any firm conclusions about the benefits and harms of different treatments for spasticity in people with TBI.
Five poor quality trials were included in this review. These involved a total of 260 participants who were randomly assigned to having their humerus fractures fixed with either a plate or a nail. Both nailing and plating had similar fracture union rates. Compared with plating, nailing was associated with an increased risk of shoulder impingement involving shoulder pain and restrictions in shoulder range of movement. Usually because of impingement, nails had to be removed more frequently than plates. The limited available evidence did not show important differences between the two surgical methods in the other outcomes reported by one or more trials. These outcomes included nerve injury, infection, healing time, operating time, blood loss and return to pre-injury occupation.
We reviewed the evidence about the effect of bronchodilators in infants with bronchiolitis. We found 30 trials that included a total of 1922 infants, in several countries. The evidence is current up to January 2014. We analyzed studies done in outpatient and inpatient settings separately. All bronchodilators were included in the review except for epinephrine because it is reviewed in another Cochrane review. Albuterol (otherwise known as salbutamol) is commonly used in studies, so we also reviewed this bronchodilator as a subgroup. We found no effect of bronchodilators on oxygen saturation. Infants hospitalized for bronchiolitis showed no significant benefit of bronchodilator treatment. This review also found that bronchodilators do not reduce the need for hospitalization, do not shorten the length of stay in hospital and do not shorten the length of the illness at home. Reviewing the subgroup of studies using albuterol (salbutamol), we found no effect of this bronchodilator on oxygen saturation or clinical scores. Side effects of bronchodilators include rapid heart beat, decrease in oxygen and shakiness. Given these side effects, little evidence that they are effective and the expense associated with these treatments, bronchodilators are not helpful in the management of bronchiolitis. This review is limited by the small number of studies that use the same measures and methods. For example, only 22 studies included only infants wheezing for the first time. Older studies included children who had wheezed before and may have had asthma. Thus these older studies favor the use of bronchodilators. Newer studies that excluded infants with prior wheezing and had a better study design do not show a benefit of bronchodilators. This review is also limited by the small number of infants included in each study. Lastly, clinical scores used to measure the effect of the bronchodilators in some studies may vary from one observer to the next, making this measure unreliable. Studies that include more infants, use better measures and have a stronger study design are needed to define the effectiveness of these medications.
Review authors, working with the Cochrane Oral Health Group, carried out a thorough search up to 15 December 2015 for studies that randomly allocated participants to different treatments for BRONJ (or to a 'placebo' condition that has no active treatment). This type of study design is known as a 'randomised controlled trial'. We only found one relevant completed study and two ongoing studies. The completed study compared people with BRONJ being treated with surgery, antibiotics and mouth rinses to people receiving the same 'standard care' with an add-on treatment called hyperbaric oxygen therapy, which is thought to increase bone renewal. There were 49 participants, most of whom had cancer. The study found that the participants in intervention group were more likely than the standard care group participants to have an improvement in their osteonecrosis at three months, but there was no clear difference between the groups when they were evaluated at six, 12 and 18 months and last contact. There was no clear difference between the groups at any time point for complete healing. These results are not reliable as the quality of the evidence is very low. The study did not assess whether there were any side effects of the treatment. The study had several important flaws: for example, there was a very small number of participants, some participants changed groups during the study and there was a loss of participants during the study. There is insufficient evidence to conclude whether hyperbaric oxygen therapy is a useful add-on to standard care in the treatment of BRONJ. There are two ongoing trials of teriparatide, a hormonal treatment for BRONJ. We found no randomised controlled trials of any other treatments for BRONJ. As there is a lack of good quality scientific evidence to decide how best to treat BRONJ, high quality trials are needed.
We included two studies, recruiting a total of 413 patients. One study looked at 201 children between six months and six years who had ventilation tubes inserted to treat glue ear or recurrent infections. Children were divided into two groups: one group was allowed to swim and bathe freely, the other group was instructed to wear ear plugs while swimming or bathing. Another study looked at 212 children between three months and 12 years who had ventilation tubes inserted (we do not know precisely what for). These children were divided into two groups: one group was allowed to swim and bathe freely, the other group was instructed not to swim and told to avoid putting their head under water when bathing. Children in both studies were followed for about one year to see how many ear infections they had and if there were any other problems. We do not have any reason to be concerned about who funded these studies. The main result we looked for was the effect that keeping ears dry had on ear infections, specifically ear discharge. One study showed that there was a small reduction in the likelihood of getting an ear infection in children who protected their ears from water with ear plugs when swimming or bathing. The effect of wearing ear plugs was to reduce the number of infections a child would have every year (on average) from 1.2 to 0.84. We think the results from this study are quite reliable. Another study showed that there was no difference in the likelihood of children getting ear infections whether they were told to avoid swimming and putting their head under water, or whether they took no precautions at all. We are uncertain whether the results from this study are reliable. Neither study showed any other important differences between the children who got their ears wet and those who kept them dry. There was no effect on how long the tubes stayed in place or on hearing (although these results were only measured in one study). No harm to any participant was reported in either study. The evidence is current to September 2015. We graded the quality of evidence for the use of ear plugs as low, which means that "further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate". We have graded the quality of evidence relating to water avoidance as very low ("we are very uncertain about the estimate"). The difference that wearing ear plugs makes appears to be very small and a child would have to wear them on average for almost three years to prevent one infection resulting in ear discharge. It may be that telling children to avoid swimming and putting their head under water makes no difference to whether or not they get ear infections, but this is very uncertain. Current expert guidelines for clinicians therefore recommend against routinely using water precautions because the limited clinical benefit is outweighed by the associated cost, inconvenience and anxiety. Future high-quality studies could be undertaken but may not be thought necessary. It is uncertain whether further trials in this area would change the findings of this review or have an impact on practice. Any future high-quality research should focus on determining whether particular groups of children benefit more from water precautions than others, as well as on developing clinical guidelines and their implementation.
Women who want to preserve the length of their vagina after radiotherapy should consider dilation. There are limited data from observational studies that suggest regular stretching of the vagina, once radiotherapy treatment is completed, might reduce the risk of scaring by a small amount. There is no evidence to support dilation therapy during radiotherapy. There are also case reports and one case series suggesting that dilation months or years after radiotherapy might help restore vaginal length. Randomised trial design has not, and may never, obtain high-quality evidence to assess vaginal dilation therapy. The available studies suggest, but cannot prove, that dilation works. However, this only applies once the radiotherapy has finished. There is an association between vaginal dilation after radiotherapy and less vaginal stenosis, but this is not proof that the benefit is due to dilation. The link between dilation and less stenosis could either be due to a beneficial effect of dilation or because women with stenosis (or who self report stenosis) are less able to use the dilator.
We included eight studies (490 adult participants). Seven studies (437 participants) investigated topical antifungals (nasal sprays or irrigations) and one study (53 participants) investigated systemic antifungals (tablets). All studies compared antifungals to placebo or no treatment. Most studies were well conducted and there was a mix of patients with chronic rhinosinusitis both with, and without, nasal polyps. At the end of at least four weeks treatment, none of the studies found that patients using antifungals (topical or systemic) had a better quality of life or less severe symptoms than patients who used placebo or had no treatment. Not many participants in the studies reported having adverse effects. Topical antifungals may lead to more nasal irritation compared with placebo. It is uncertain if patients taking topical antifungals have more headaches or nosebleeds than with placebo. For systemic antifungals, it is uncertain if patients using antifungals have more problems with their liver (hepatic toxicity) than with placebo. Systemic antifungals may lead to fewer patients with gastrointestinal disturbances compared to placebo. We found no studies that compared antifungal treatment with other treatments for chronic rhinosinusitis. We assessed the quality of the evidence as either low (further research is very likely to have an important impact on our confidence in the result) or very low (any estimate of the result is very uncertain), as some of the results are only from one or two studies, which do not have a lot of participants. Moreover, the different studies reported outcomes using different measurement scales making it difficult to draw conclusions. Due to the very low quality of the evidence, it is uncertain whether or not the use of topical or systemic antifungals has an impact on patient outcomes in adults with chronic rhinosinusitis compared with placebo or no treatment. More trials are needed to assess well-defined patient populations (such as the AFRS subgroup) and to evaluate other antifungals that have not been assessed in randomised controlled trials.
We included randomized trials that recruited adults with ischemic stroke, at any time after onset. We included any kind of stem cell or method of administration. We identified seven randomized trials, involving 401 participants. Overall, stem cell transplantation was associated with a reduced neurological impairment, but not with a better functional outcome. No safety concerns were raised. The certainty of the evidence ranged from low to very low because of the risk of bias in the included studies, the lack of precision of the results, and different designs. More well-designed randomized controlled trials are needed.
We found a total of 27 Cochrane ART reviews of high quality that could be included for this overview. These reviews aimed to report on OHSS in cycles of IVF or ICSI. We did not include reviews of intrauterine insemination and ovulation induction. The evidence is current to 12 December 2016. Of the 27 reviews included in this overview, 10 reviews had not been updated in the past three years. Seven reviews described interventions that provided a beneficial effect in reducing OHSS rates, and we categorised one additional review as 'promising'. Of the effective interventions, all except one had no detrimental effect on pregnancy outcomes. Evidence of at least moderate quality evidence indicates that clinicians should consider the following interventions in ART cycles to reduce OHSS rates. • Metformin treatment before and during an ART cycle in women with PCOS (moderate-quality evidence). • Gonadotrophin-releasing hormone (GnRH) antagonist protocol in ART cycles (moderate-quality evidence). • GnRH agonist (GnRHa) trigger in donor oocyte or 'freeze-all' programmes (moderate-quality evidence). Evidence of low or very low quality evidence suggests that clinicians should consider the following interventions in ART cycles to reduce OHSS rates. • Clomiphene citrate for controlled ovarian stimulation in ART cycles (low-quality evidence). • Cabergoline around the time of human chorionic gonadotrophin (hCG) administration or oocyte pickup in ART cycles (low-quality evidence). • Intravenous fluids (blood plasma expanders) around the time of hCG administration or egg pickup in ART cycles (very low-quality evidence). • Progesterone for luteal phase support in ART cycles (low-quality evidence). A promising intervention that needs to be researched further is coasting (withholding gonadotrophins) for reduction of OHSS. On the basis of this overview, we must conclude that evidence is currently insufficient to support the widespread practice of freezing all embryos and replacing them at a later time when OHSS has dissolved. Clinicians can use the evidence summarised in this overview to choose the best treatment regimen for individual patients - a regimen that not only reduces the chance of developing OHSS but does not compromise pregnancy outcomes. However, results of this overview are limited by the lack of recent primary studies or updated reviews. Furthermore, this overview can be used by policymakers in developing local and regional protocols or guidelines and can reveal knowledge gaps for future research.
Evidence from this review of 630 people in two trials suggests that, in patients with polycythaemia vera and with no clear indication or contraindication to aspirin therapy, low-dose aspirin may reduce the risk of thrombotic and all-cause mortality. No data were provided on mortality from bleeding episodes. No studies in participants with essential thrombocythaemia and with antiplatelet therapy other than aspirin have been published.
We searched for evidence that OWSC could be used to identify which patients with inoperable MBO would recover with conservative management. We also wanted to know if OWSC increased the likelihood of recovery from MBO, reduced hospital stay or improved prognosis. Finally, we wished to know what side effects OWSC might cause for patients with MBO. We conducted the search in June 2017 and found one study. It only recruited nine participants and did not fully report on the outcomes of using OWSC in MBO. We found insufficient evidence that OWSC can identify which patients with MBO will recover with conservative management. We found insufficient evidence that patients with MBO benefit from OWSC in terms of length of hospital stay, recovery time or survival. No conclusions could be made about side effects from OWSC. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. We rated the quality of the evidence as very low due to the lack of studies reporting on the benefits of using OWSC in MBO and the only study we found reporting on side effects recruited very few participants (nine). The low quality of the evidence means that we are very uncertain about the use of OWSC in the management of MBO and cannot confirm its benefits or harms in patients with this condition.
. We searched for trials in July 2015 and April 2017, using the Cochrane Schizophrenia Group's register of trials. The review includes 14 studies investigating the use of cholinergic drugs compared with placebo. All studies randomised small numbers of participants (five to 60 people) with schizophrenia or other chronic mental illnesses who had also developed antipsychotic-induced tardive dyskinesia. . We found the effects of both older and newer cholinergic drugs to be unclear as too few and too small studies are available and do not yield great evidence and leave many questions unanswered. . The available evidence is weak, limited, and small scale. It is not possible to recommend these drugs as a treatment for tardive dyskinesia based on our findings. To fully investigate whether the use of cholinergic drugs have any positive effects for people with tardive dyskinesia, there would have to be well-designed, larger, longer-term studies, particularly on new cholinergic drugs currently being used for treating Alzheimer’s disease. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/
The aim of this review was to assess the effectiveness of using the telephone to deliver interventions to improve the health of PLHIV compared to standard care. A comprehensive search of various scientific databases and other resources found 11 relevant studies. All of the studies were performed in the United States, and so the results may not apply to other countries, particularly developing countries. Some studies were aimed at any HIV positive person in the area in which the study was carried out, and others focused on specific groups of people, such as young substance using PLHIV, or older PLHIV. There were a lot of differences in the types of telephone interventions used in each study. There was some evidence that telephone interventions can improve medication adherence, reduce risky sexual behaviour, and reduce symptoms of depression in PLHIV. However, there were also a number of studies that suggested that telephone interventions were no more effective than usual care alone. We need more studies conducted in different settings to assess the effectiveness of telephone interventions for improving the health of PLHIV.
We conducted a comprehensive search of medical literature up to 5 July 2013 to find randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) and quasi-randomized controlled trials (e.g. allocation by hospital record number or date of birth) comparing computer-assisted surgery (CAS) of the ACL or PCL with conventional operating techniques not involving CAS in adults. We found five studies for inclusion in this review. These studies involved 366 participants, mainly female (70%), aged 14 to 53 years. All five trials involved ACL reconstruction. We were uncertain about the reliability of study findings due to poor reporting of trial methods and, sometimes, results. Our assessment of the quality of the evidence available for individual outcomes ranged from 'moderate' quality (which means further research may change the estimate) to 'very low' quality (which means we are very uncertain about the estimate). The trials provided some moderate quality evidence that there was no difference between computer-assisted surgery and conventional surgery for patient-reported knee function. There was low quality evidence of no difference between the two groups in self-reported function score and very low quality evidence of no difference in a score measuring activity levels. There was low quality evidence of no difference between the two treatment groups in the number of people assessed by clinicians as having a normal or nearly normal knee function at the final follow-up time. No adverse post-surgical events were reported in two trials; this outcome was not reported by the other three trials. CAS took longer to do than conventional surgery (from 9 to 27 minutes longer). Overall, the currently available evidence does not indicate that CAS in knee ligament reconstruction improves outcome compared with conventional surgery.
We included two randomized controlled trials with a total of 2560 participants set in Australia and Tanzania. One trial compared a combined strategy of face washing plus tetracycline (an antibiotic) ointment with tetracycline ointment alone for up to one year. The second trial compared four intervention groups for three months in children who already had follicular trachoma: a combined strategy of face washing plus tetracycline eye drops, face washing alone, tetracycline eye drops alone, and no treatment. The evidence is current to January 2015. Both trials reported the number of children with active trachoma as an outcome measure; one trial also reported the number of children with severe trachoma and the percentage of clean faces after one year. One trial reported that face washing was effective in increasing facial cleanliness and in reducing severe trachoma at one year; the second trial did not show that eye washing alone or in combination with tetracycline eye drops reduced follicular trachoma amongst children who had follicular trachoma at time of enrollment. The two included trials were of uncertain risk of bias due to not reporting many aspects of the trial designs.
We identified 49 randomised controlled trials (over 140,000 school children) of interventions aiming to prevent children who had never smoked from becoming smokers. At longer than one year, there was a significant effect of the interventions in preventing young people from starting smoking. Programmes that used a social competence approach and those that combined a social competence with a social influence approach were found to be more effective than other programmes. However, at one year or less there was no overall effect, except for programmes which taught young people to be socially competent and to resist social influences. A smaller group of trials reported on the smoking status of all people in the class, whether or not they smoked at the start of the study. In these trials with follow-up of one year or less there was an overall small but significant effect favouring the controls. This continued after a year; for trials with follow-up longer than one year, those in the intervention groups smoked more than those in the control groups. When trials at low risk of bias from randomisation, or from losing participants, were examined separately, the conclusions remained the same. Programmes led by adults may be more effective than those led by young people. There is no evidence that delivering extra sessions makes the intervention more effective.
Randomised controlled studies compare treatments to find out if they are truly effective. We searched for randomised studies comparing non-invasive ventilation to routine care for adults with acute cardiogenic pulmonary oedema. We compared studies treating people with non-invasive ventilation versus medical care. Medical care includes therapies such as providing extra oxygen and water pills to patients. The evidence upon which this review is based is current to September 2018. We sought to address if non-invasive ventilation in adults with acute cardiogenic pulmonary oedema reduces rates of deaths, the need for a breathing tube, and heart attacks. We found 24 studies with 2664 participants comparing non-invasive ventilation to medical care alone. Non-invasive ventilation may decrease the chances of dying in hospital. The quality of results for studies reporting death in hospital was low. Studies were poorly conducted, and results were not similar across studies. In addition, non-invasive ventilation probably reduces the chances of needing a breathing tube. The quality of results for studies reporting breathing tube rates was moderate. Studies evaluating breathing tube rates were poorly conducted. Non-invasive ventilation probably has little or no effect on getting a heart attack. The quality of results for studies reporting heart attack rates was moderate, and studies had inconsistent results for this outcome. We are unsure if the length of hospital stay is improved with non-invasive ventilation. The quality of results for studies reporting hospital length of stay was very low, which was due to poor study conduct and inconsistent results. Finally, non-invasive ventilation may make little or no difference to adverse events (complications), compared to medical care. The quality of results for studies reporting adverse events was low. Studies evaluating adverse events were poorly conducted and had inconsistent results.
We looked for studies which compared steroid injections in the ear with placebo in patients with Ménière's disease or syndrome. Only one study satisfied the prespecified inclusion criteria for this review. This study demonstrated a benefit of this treatment for patients with Ménière's disease; at 24 months the patients in the treatment group had far fewer episodes of vertigo. The results of this review are encouraging, however as it is based solely on the results of a single study, further research is required.
The review of trials found that there was conflicting evidence about the benefit of therapists teaching men to contract their pelvic floor muscles for either prevention or treatment of urine leakage after radical prostate surgery for cancer. However, information from one large trial suggested that men do not benefit from seeing a therapist to receive pelvic floor muscle training after transurethral resection (TURP) for benign prostatic enlargement. Overall, there was insufficient evidence to demonstrate a beneficial effect from pelvic floor muscle training. Of three external compression devices tested, one penile clamp seemed to be better than the others. This one penile clamp needed to be used cautiously because of safety risks. In future updates it may be worth considering two separate reviews, looking separately at 'treatment' and 'prevention' trials. More research that is of better quality is also needed to assess conservative management.
The review findings indicate that listening to music during planned caesarean section under regional anaesthesia may improve pulse rates and birth satisfaction scores, although the effect sizes were not large enough to indicate a clinically beneficial effect. The review authors identified one controlled trial that randomly assigned 76 women who listened to their preferred music through earphones, or to standard care, but data were available for only 64 women. The music was provided from the beginning of anaesthesia to the end of surgery. The women's heart rates were reduced by some seven beats/minute when measured at the end of contact with the newborn during the intra-operative period and after the surgeon had completed skin suture. Birth satisfaction scores were increased by a mean of 3.4 points on a 35-point scale when women listened to music. Respiration rates were no different for the two groups and neither were levels of anxiety, which decreased at the end of contact with the newborn and again after closing the skin, with no clear difference with or without music. The trial was from Taiwan and reporting of trial methodology was poor.
Two randomised controlled trials were included in this review involving a total of 271 women with twin pregnancies at 37 weeks' gestation. One of the two trials (involving 235 women) was of high quality, and the quality of the second trial (involving 36 women) was unclear. There were no differences shown between the group of women who had an elective birth at 37 weeks' gestation and the group of women who waited for labour to start spontaneously for the outcomes: birth by caesarean section, perinatal (fetal or neonatal) death or serious perinatal morbidity, or maternal death or serious maternal morbidity. No other differences between the two groups of women were shown for other pregnancy and birth complications or for complications for the infant. Elective birth at 37 weeks' gestation compared with ongoing expectant management for women with uncomplicated twin pregnancies does not appear be associated with an increased risk of harms.
We found one small trial undertaken in 28 children aged 1 to 16 years with confirmed peanut allergy. The study did not include children who had moderate to severe asthma or who had had severe anaphylaxis (a severe allergic reaction that may result in death) because of their peanut allergy. The authors randomised children to intervention or placebo in a 2:1 ratio. Intervention arm children received peanut flour whereas control arm participants received oat flour. The 48-week trial showed that treatment with peanut OIT enabled children receiving OIT to substantially increase the amount of peanut flour they ate in comparison with those in the placebo arm without having an allergic reaction.  However, almost half of the children (nine out of 19) receiving OIT had an allergic reaction due to the OIT which required antihistamines, and two had more serious reactions to the treatment which required adrenaline (epinephrine). Although promising, based on the findings of this one small trial, we cannot recommend that peanut OIT be used routinely for people with peanut allergy. There is a need for further larger studies investigating safer OIT regimens and establishing the long-term effectiveness of OIT after treatment is stopped.
The review of trials found that a few days of using acetazolamide can improve the level of oxygen in the blood of people with COPD. It is not clear if this leads to better outcomes, so more research is needed. Not enough data were reported on the safety of the drug.
The review of trials found that a letter of invitation, mailed educational material, a phone call and some combined actions (such as a letter of invitation plus a phone call and training activities plus reminders) all seem to increase numbers of women participating. However it is not known which of these work better. Other interventions (such as a home visit) have not been proven to work.
We examined research up to 17 February 2015. We included research studies that had women over 16 years of age attending any healthcare setting. Our search generated 12,369 studies and we eventually included 13 studies that met the criteria described above. In all, 14,959 women had agreed to be in those studies. Studies were in different healthcare settings (antenatal clinics, women's health/maternity services, emergency departments, and primary care centres). They were conducted in mainly urban settings, in high-income countries with domestic violence legislation and developed support services to which healthcare professionals could refer. Each of the included studies was funded by an external source. The majority of the funding came from government departments and research councils, with a small number of grants/support coming from trusts and universities. Eight studies with 10,074 women looked at whether healthcare professionals asked about abuse, discussed it, and/or documented abuse in participating women's records. There was a twofold increase in the number of women identified in this way compared to the comparison group. The quality of this evidence was moderate. We looked at smaller groups within the overall group, and found, for example, that pregnant women were four times as likely to be identified by a screening intervention as pregnant women in a comparison group. We did not see an increase in referral behaviours of healthcare professionals but only two studies measured referrals in the same way and there were some shortcomings to these studies. We could not tell if screening increased uptake of specialist services and no studies examined if it is cost-effective to screen. We also looked to see if different methods were better at picking up abuse, for example, you might expect that women would be more willing to disclose to a computer, but we did not find one method to be better than another. We found an absence overall of studies examining the recurrence of violence (only two studies looked at this, and saw no effect) and women's health (only one study looked at this, and found no difference 18 months later). Finally, many studies included some short-term assessment of adverse outcomes, but reported none. There is a mismatch between the increased numbers of women picked up through screening by healthcare professionals and the high numbers of women attending healthcare settings actually affected by domestic violence. We would need more evidence to show screening actually increases referring and women's engagement with support services, and/or reduces violence and positively impacts on their health and wellbeing. On this basis, we concluded that there is insufficient evidence to recommend asking all women about abuse in healthcare settings. It may be more effective at this time to train healthcare professionals to ask women who show signs of abuse or those in high-risk groups, and provide them with a supportive response and information, and plan with them for their safety.
The purpose of this systematic review was to examine the effectiveness and safety of curcumin therapy for the maintenance of remission in patients with ulcerative colitis (UC), a chronic inflammatory condition of the colon. Currently available agents for the management of this condition have been reported to result side effects, particularly when used for prolonged periods. This review includes one randomized trial with a total of 89 participants. All patients received treatment with sulfasalazine or mesalamine (drugs containing 5-aminosalicylic acid). Fewer patients in the curcumin group relapsed at six months compared to patients who received placebo (e.g. fake drug). However, this result was not statistically significant. Patients in the curcumin group had significantly lower disease activity index and endoscopic index scores at six months than patients in the placebo group. No serious side effects were reported. A total of nine mild side effects were reported in seven patients. These side effects included a sensation of abdominal bulging, nausea, a brief increase in blood pressure, and a brief increase in the number of stools. The results of this systematic review suggest that curcumin may be a safe and effective therapy for maintenance of remission in ulcerative colitis when given as additional therapy with mesalamine or sulfasalazine. Further research is needed to confirm any possible benefit of curcumin for maintenance therapy in ulcerative colitis.
We included seven trials with 1497 women who had HER2-positive metastatic breast cancer in this review. They were assigned by chance to receive trastuzumab with or without chemotherapy (taxane, anthracycline or capecitabine in four studies), hormonal therapy (aromatase inhibitors including letrozole or anastrozole in two studies) or targeted therapy (lapatinib in one study). Women treated with trastuzumab were followed up until disease progression in five studies and beyond disease progression in two studies. The length of trastuzumab administration varied between 8.7 and 30 months, and follow-up averaged two years after starting trastuzumab. All studies found that trastuzumab extends time to disease progression, with gains varying between two and 11 months, and in five studies it extended time to death by between five and eight months. However, some patients develop severe heart toxicity (congestive heart failure) during treatment. While trastuzumab reduces breast cancer mortality by one-fifth, the risk of heart toxicity is between three and four times more likely. If 1000 women were given standard therapy alone (with no trastuzumab) about 300 would survive and 10 would have heart toxicities. With the addition of trastuzumab to this treatment, an additional 73 would have their lives prolonged, and an additional 25 would have severe heart toxicity. Omitting the anthracycline-trastuzumab arms (which would not be regarded as standard of care) 21 patients would have severe heart toxicity (11 more than the chemotherapy alone group). These heart toxicities are often reversible if the treatment is stopped once heart disease is discovered. Women with advanced disease might choose to accept this risk. On balance, this review shows that with trastuzumab the time to disease progression and survival benefits outweigh the risk of heart harm. Trastuzumab does not increase the risk of haematological toxicities, such as neutropenic fever and anaemia; however, it seems to raise the risk of neutropenia. There were insufficient data on the impact of trastuzumab on quality of life, treatment-related deaths and brain metastases to reach a conclusion for these outcomes. We rated the overall quality of the evidence as moderate, with the main weaknesses being the fact that all studies included were open-label (not blinded), which may have affected the outcome assessments for time to disease progression and toxicities, and that two studies have not published their results for mortality. Furthermore, the recruitment in three out of seven studies was stopped early and in three trials more than 50% of patients in the control groups were permitted to switch to the trastuzumab arms at disease progression, making it more difficult to understand the real net benefit of trastuzumab on mortality. The evidence to support the use of trastuzumab beyond disease progression is limited. It is important to highlight that, although trastuzumab is used for women with HER2-positive early breast cancer, the women enrolled in these metastatic trials were not previously treated with trastuzumab. The effectiveness of trastuzumab for women relapsing after adjuvant trastuzumab is still an open issue, although it is likely that it is offered to the majority of them.
The researchers identified 14 studies that included a total of 1805 participants. Nine studies (779 participants) compared budesonide to conventional corticosteroids, three studies (535 participants) compared budesonide to a placebo (e.g. a sugar pill), and two studies (491 participants) compared budesonide to mesalamine (an anti-inflammatory drug composed of 5-aminosalicylic acid). Ten studies were judged to be of high quality. Four studies were judged to be of low quality. Budesonide was superior to placebo for induction of remission. An increase in side effects was not seen with budesonide compared to placebo. Withdrawals due to disease worsening were similar in budesonide and placebo groups. Budesonide patients were more likely than placebo patients to experience adrenal suppression a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. Budesonide was significantly less effective than conventional steroids for induction of remission in people with Crohn's disease. However, fewer side effects occurred in those treated with budesonide compared to conventional steroids and budesonide was better than conventional steroids in preserving adrenal function. One study (n = 182) found budesonide to be superior to mesalamine for induction of remission in patients with Crohn's disease whereas another study found no difference in remission rates. The current evidence does not allow for a firm conclusion on the relative efficacy of budesonide compared to 5-aminosalicylic products. Budesonide is more effective than placebo for induction of remission in Crohn's disease. Although budesonide is less effective than conventional steroids for induction of remission the likelihood of side effects and adrenal suppression is lower than with conventional steroids.
Our systematic review identified 15 randomised studies with 1550 patients comparing CRRT with IRRT. We did not find any difference between CRRT and IRRT with respect to mortality, renal recovery, and risk of haemodynamic instability or hypotension episodes.
Although four randomised controlled trials met the inclusion criteria, one was excluded because of poor methodology. The three remaining trials compared testosterone treatment with placebo in a total of 109 middle-aged to elderly people, predominantly men. The participants had symptoms of lower limb atherosclerosis, predominantly intermittent claudication. The trials were published from 1967 to 1971 and all took place in Denmark. Testosterone did not provide any clear improvement in the symptoms reported by the participants, walking distance or other objective tests for peripheral arterial disease including leg muscle blood flow. The dose of testosterone in the trials varied between 300 mg taken by mouth every two weeks for three months to a lower (100 mg) oral dose taken more often and 200 mg given by intramuscular injection, first weekly then every two weeks for six months. Side effects were poorly reported except for subjective sexual functioning, which did seem to improve with testosterone treatment. No trials investigated oestrogens in women with lower limb atherosclerosis. Trials by the Women's Health Initiative (published in 2004) have shown that oestrogen and progestin does not confer any protection against peripheral arterial disease in healthy postmenopausal women or reduce the risk of coronary events in postmenopausal women with coronary heart disease.
We included two randomized controlled studies (clinical trials where people are randomly put into one of two or more treatment groups) with 297 men comparing PUL to sham surgery (participants are made to believe they received treatment, while in reality they did not) or transurethral resection of prostate (TURP: removing the excess prostate growth using a camera and an electrically activated resecting loop inserted via the penis). The average age of the participants was 65.6 years. Compared to sham surgery up to three months, PUL may improve urinary symptoms and likely improves quality of life without additional unwanted side effects after surgery. In the short term, there were no additional surgeries because PUL did not work. PUL likely does not make erections or ejaculation worse. Compared to TURP up to 24 months, PUL may be less effective in relieving urinary symptoms, but result in similar quality of life. PUL may preserve ejaculation, but may have less unwanted effects on erections than TURP. However, we are either very uncertain or have no evidence about serious unwanted side effects or the need for additional treatment after surgery. Findings of this review are up-to-date until 31 January, 2019. The certainty of evidence for most outcomes was low. This means that the true effect may be substantially different from what this review shows.
Only one small randomized trial of 54 men was included in this review. Based on the results of this trial, which used non-valid ways to measure symptom improvements, allopurinol cannot be recommended. Further studies of allopurinol treatment, enrolling larger numbers of men and using standard and validated measures to measure symptom improvements, are necessary to determine whether allopurinol is an effective treatment for chronic prostatitis.
We performed a comprehensive literature search for randomized controlled trials and found one study that addressed our question. This study was a randomized trial of adults undergoing surgery to remove their bladder. They received either 12 mg alvimopan of up to 15 doses over seven days (143 patients) or placebo (137 patients). This study was conducted at centres that did many of these operations (at least 50 per year), had experienced surgeons and also used other measures such as asking patients to get out of bed soon after surgery to hasten bowel recovery. We found that patients who receive alvimopan short-term probably tolerate solid food faster, are discharged from the hospital more quickly and have fewer major adverse events. We did not find any differences with regards to these patients' need to be readmitted to hospital, their risk of heart problems or their need for narcotic pain medications. Patients taking alvimopan were less likely to have a tube placed back into their stomach. The quality of evidence was rated as at least moderate as per GRADE for all primary outcomes. This means that our estimates of how well alvimopan works is likely close to how well it really works although there is a possibility that it may be different.
This review is up-to-date to May 2014. We included 26 trials involving 17,011 participants: 24 trials assessed lowering blood pressure, one trial tested raising blood pressure, and two trials assessed what to do with drugs taken before stroke. All studies took place in hospitals that were used to treating people with stroke. Not all trials contributed information to all outcomes, and we have used data that were available in publications. There is insufficient evidence to say that lowering blood pressure saves lives or reduces disability in people with acute stroke. Immediately restarting blood pressure-lowering drugs taken before the stroke may increase disability. More research is needed to identify those people who are most likely to benefit from altering blood pressure in acute stroke, the time window in which the treatment is likely to be of benefit, what types of stroke are likely to respond favourably, and the environment in which such treatment may be best given in routine practice.
We identified two randomized controlled trials involving a total of 147 participants (current until January 2016). Due to differences in the techniques and outcomes measured, we were unable to combine the data from these studies. In one study, participants were randomized to receive either subintimal angioplasty (SIA) with stenting or remote endarterectomy (RE) (a surgical procedure to unblock the artery) with stenting. This study showed significantly better vessel patency (no obstruction) with RE compared to SIA. Three-year follow-up results showed clinical improvement measured by a Rutherford classification improvement in 64% of participants in the SIA group compared to 80% of participants in the RE group. Postexercise ankle brachial index improvements (0.2) were reported in 70% of SIA participants compared to 82% of RE participants. The technical success rate was 93% for SIA participants and 96% for RE participants. Primary patency was 56.8% in SIA compared to 76.5% in RE at 24 months, and 47.7% in SIA and 62.7% in RE at 36 months. Assisted primary patency was 52.3% in SIA compared to 70.6% in RE at 36 months. Secondary patency favored RE at 36 months. Limb salvage at three years' follow-up was 95% in the SIA group and 98% in the RE group. There were no deaths during or around the time of the procedure, but complications occurred in two SIA participants and three RE participants. The other study, which compared the SIA OUTBACK device with a manual re-entry technique, reported that technical success was achieved in all cases but did not report on clinical improvement. The primary 6-month patency rate was 100% in the OUTBACK group (26 of 26 participants) compared to 96.2% in the manual re-entry group (25 of 26 participants). The primary 12-month patency rate was 92.3% in the OUTBACK group (24 of 26 participants) compared to 84.6% in manual group (22 of 26 participants). Patency rates at 24 and 36 months were not reported. Limb salvage rates at 36 months were not reported. No complications were reported. Both studies were at an overall low risk of methodological bias, but the quality of the evidence is low due to small study size and the small number of studies. Moreover, the two included trials differed from each other in the techniques and control used, preventing the combining of trial results. Since we included only two small studies, we doubt the completeness and applicability of the evidence presented in this review. Further studies are needed to reach a definitive conclusion.
In this review we have included results from 27 randomised trials with more than 12,000 women. All of the trials examined telephone support versus usual care (no additional telephone support). In two trials women received automated text messages. We did not identify any trials comparing different types of telephone support (for example, text messaging versus one-to-one calls). All but one of the trials were carried out in high-resource settings. The majority of studies examined support provided via telephone conversations between women and health professionals although a small number of trials included telephone support from peers. Many of the results described in the review are based on findings from only one or two studies. Overall, results were inconsistent and inconclusive. Telephone support may increase women's overall satisfaction with their care during pregnancy and the postnatal period; although results for both periods were from only two studies. There was no consistent evidence confirming that telephone support reduces anxiety during pregnancy or after the birth of the baby. Evidence from two trials showed that women who received support had lower average depression scores in the postnatal period but without clear evidence that women who were supported were less likely to have a diagnosis of depression. Results from trials encouraging breastfeeding through telephone support were also inconsistent, although there was some evidence that telephone support may increase the duration of breastfeeding. There was no strong evidence that women receiving telephone support were less likely to be smoking at the end of pregnancy or during the postnatal period. For infant outcomes, such as preterm birth and infant birthweight, overall, there was little evidence. Where evidence was available, there were no clear differences between groups. There remains uncertainty regarding the benefit of telephone support and despite some encouraging findings, there is insufficient evidence to recommend routine telephone support for women accessing maternity services.
Information and communication technologies (ICTs) are technologies that help gather, store, process and share information electronically.  Examples of ICTs are electronic medical records, medical journals and databases on the internet, videoconferencing for doctor appointments, or systems on the internet to give feedback to doctors so they can improve the care they provide.  ICTs have the potential to improve health care and the health of patients.  But even though computers are being used more and more in hospitals, not all health care professionals use ICTs.   For this reason, there are many strategies to try and promote the use of ICTs.  Strategies can include training groups of health care professionals to use a specific ICT, or teaching someone one-on-one to use an ICT, or simply providing training materials. A review of the effects of different strategies to promote the use of ICTs was conducted.  After searching for all relevant studies, 10 studies were found.  The evidence shows that some ways, such as group training, or one-on-one training sessions, or providing training materials, may improve the use of ICTs.  But overall, it is still uncertain whether some strategies are effective.  More research is needed.
Eleven studies involving a total of 2093 participants were included. The evidence was dominated by one large multicentre trial of 1319 participants. The methods of two studies were flawed such that their results were likely to be biased. The remaining studies were at a lower risk of bias. The trials evaluated five different comparisons of interventions. Only the two comparisons tested by more than one trial are reported here. These were reamed versus unreamed intramedullary nailing (six trials) and Ender nail versus interlocking nail (two trials). The review found no evidence of a significant difference between reamed and unreamed intramedullary nailing in re-operations for complications, nor in various complications such as nonunion (where the bone fails to heal). However, reamed nailing was more associated with a lower implant failure, such as broken screws, than unreamed nailing. Moreover, there was some weak evidence that reamed nailing may be associated with fewer major re-operations for non-union when used for closed fractures (where the skin remains intact) compared with open (where the skin is broken) fractures. The review also found that the Ender nail resulted in more re-operations and deformity (malunion) than an interlocking nail. The review concluded that there is insufficient evidence to draw definitive conclusions on the best type of, or technique for, intramedullary nailing for tibial shaft fractures in adults.
From literature searches updated to 5 January 2016, 10 randomised controlled trials that enrolled 1644 infants were included. We are not aware of any financial support from the industry for the included studies. In this update of the review there was no significant reduction in the rate of chronic lung disease at 36 weeks' postmenstrual age. A significant reduction in the combined outcome of death or chronic lung disease at 36 weeks' postmenstrual age among all randomised neonates and among survivors was noted. Even though the results were significant, the upper confidence interval was infinity (i.e. we would have to treat every baby with inhaled steroid to prevent one baby dying or developing chronic lung disease at 36 weeks' postmenstrual age). This would not be acceptable in clinical practice. A lower rate of reintubation (the need for the insertion of a tube into the airway) was noted in the steroid group compared with the control group in one large study. There were no statistically significant differences in short- and long-term complications between groups. The results of the long-term follow-up of one large study is awaited. In general the quality of the studies was good.
We systematically analysed the published trials comparing the usefulness of FG as a small-vessel sealing agent. Eighteen randomised controlled trials on 1252 people were retrieved following bibliographic searches on standard medical databases. There were significant clinical and methodological differences among the included trials. The use of FG following breast and axillary surgery did not reduce the incidence of postoperative seroma, mean volume of seroma, wound infections, postoperative complications and the length of hospital stays. FG reduced the total volume of drained seroma and the duration of persistent seroma requiring frequent aspirations. This review showed no overall benefit of using FG. Although this conclusion is based on the combined analysis of 18 trials, the majority of these were of poor quality due to flaws in trial methods. Therefore, this conclusion should be taken cautiously and a major, multicentre, high-quality randomised controlled trial on people undergoing breast and axillary surgery for breast cancer is required to corroborate this conclusion.
Cabergoline has been compared with inactive placebo in two smaller and shorter (6 - 12 weeks) studies and one larger, medium term trial (24 weeks). These trials included 268 patients with Parkinson's disease and motor complications. The average reduction in the time patients spent in the immobile off state was 1.1 hours greater with cabergoline compared with placebo, although this was not statistically significant. Inadequate data on dyskinesia was collected to allow a conclusion to be drawn. A small but significant advantage of cabergoline over placebo was seen in one study for activities of daily living and physical functioning. No such advantage was seen in one other study due to small numbers of patients and the comparatively low doses of cabergoline used. Levodopa dose reduction was greater with cabergoline by 145 mg per day. There was a trend towards more side effects with cabergoline but towards fewer withdrawals from cabergoline treatment. In the management of the motor complications seen in Parkinson's disease, cabergoline can be used to reduce levodopa dose and modestly improve motor function and activities of daily living with an acceptable side effect profile. This is based on, at best, medium term evidence. Further long term trials are required to compare the newer with the older dopamine agonists, particularly in terms of quality of life and cost.
We searched for clinical trials to January 2019 looking at the benefits and harms of continuous injection of a local anaesthetic after surgery to remove the bowel through a vertical cut in the abdomen. We looked for trials comparing local anaesthetic to an inactive substance (placebo) such as salty water (normal saline). We found six clinical trials including 541 participants. Most participants were aged 55 to 65 years, of varying health status from fit and healthy to having a severe systemic disease (a disease that affects the whole body). In people who received a local anaesthetic, pain at rest, pain on movement, and requirement for morphine-like pain killers were reduced on the first day after surgery compared to people who received an inactive substance. People who received a local anaesthetic also opened their bowels about half a day earlier and were discharged from hospital about a day earlier compared to people who received an inactive substance. We did not find a difference between people who received a local anaesthetic and those who received an inactive substance in the rates of any serious complications after surgery until hospital discharge. We rated the certainty of the evidence from studies using four levels: high, moderate, low, very low. Reasons for downgrading the certainty of the evidence included limitations problems with the design of the studies, missing data, differences between trials and how the outcomes were measured, and the small number of participants. We need more high-quality trials to evaluate this treatment, especially its effects on recovery after surgery, side effects and complications. We rated the certainty of the evidence for pain after surgery at rest and the length of hospital stay as high, meaning that we are very confident in the findings about the effects of the treatment on these outcomes. We rated the certainty of the evidence for the requirement for morphine-like pain killers and the time until the first bowel movement as moderate. This means that we are moderately confident in the findings about the effects of the treatment on these outcomes. We rated the certainty of the evidence for pain after surgery on movement and the rates of any serious complications after surgery until hospital discharge as low, meaning that we have limited confidence in the findings about the effects of the treatment on these outcomes.
We looked at evidence from 34 studies enrolling 3033 children. Fourteen of 21 studies, in children with their first episode of nephrotic syndrome, evaluated prednisone for two or three months compared with longer durations. Thirteen studies evaluated different corticosteroid regimens in children with frequently relapsing disease (FRNS). Studies were of variable methodological quality with only about half of the studies at low risk of bias. Among studies of long versus shorter duration of prednisone, older studies at high or unclear risk of bias tended to over-estimate the effect of longer course therapy compared with new studies at low risk of bias. Studies at low risk of bias found no significant differences in the risk of relapse or the development of FRNS between prednisone given for three to six months compared with two or three months. Therefore there is no benefit of increasing the duration of prednisone beyond two or three months in the initial episode of SSNS. Based on four studies in children with frequently relapsing nephrotic syndrome, prednisone given for five to seven days at the onset of a viral infection reduces the risk of relapse. This review updates information previously published in 2000, 2003, 2005 and 2007. The addition of three new studies evaluating different durations of prednisone in the first episode of nephrotic syndrome has changed the conclusions expressed in previous versions of this review
This Cochrane Review summarises trials evaluating the effects of directly observed therapy (DOT) for treating people with tuberculosis (TB) or people on prophylaxis to prevent active disease compared to self-administered treatment. After searching for relevant trials up to 13 January 2015, we included 11 randomized controlled trials, enrolling 5662 people with TB, and conducted between 1995 and 2008. What is DOT and how might it improve treatment outcomes for people with TB DOT is one strategy to ensure that patients with TB take all their medication. An 'observer' acceptable to the patient and the health system observes the patient taking every dose of their medication, and records this for the health system to monitor. The World Health Organization currently recommends that people with TB are treated for at least six months to achieve cure. These long durations of treatment can be difficult for patients to complete, especially once they are well and need to return to work. Failure to complete treatment can lead to relapse and even death in individuals, and also has important public health consequences, such as increased TB transmission and the development of drug resistance. What the research says Overall, cure and treatment completion in both self-treatment and DOT groups was low, and DOT did not substantially improve this. Small effects were seen in a subgroup of studies where the self-treatment group were monitored less frequently than the DOT group. There is probably no difference in TB cure or treatment completion when the direct observation was conducted at home or at the clinic (moderate quality evidence). There is probably little or no difference in TB cure direct observation is conducted by a community health worker or family member (moderate quality evidence) and there may be little or no difference in treatment completion either (low quality evidence). Direct observation may have little or no effect on treatment completion in injection drug users (low quality evidence). The authors conclude that DOT on its own may not offer the solution to poor adherence in people taking TB medication.
This review assessed if knowing the cervical length can prevent preterm birth. We included seven randomised controlled studies, which involved 923 pregnant women at 14 to 32 weeks' gestation. One study included expectant mothers with twins, without any symptoms of preterm birth or labour, and looked at the number of babies born prematurely before 36 weeks. Four studies included expectant mothers of single babies with threatened preterm labour, and one study involving women with premature rupture of the membranes looked at the safety of transvaginal ultrasound. One trial included expectant mothers with singleton pregnancies who did not have any symptoms of preterm birth or labour to look at the efficacy of transvaginal ultrasound cervical length screening. All studies used transvaginal ultrasound to assess cervical length. For women with twin pregnancies and not showing symptoms of preterm birth, we are unclear of the impact of knowing the cervical length on whether babies are born before 34 weeks' gestation, or their gestational age at birth (1 study, 125 women), because we assessed the quality of the evidence to be very low. For women with a single baby and threatened preterm labour, knowledge of their cervical length may have led to a longer pregnancy by about four days (4 studies, 410 women), but the evidence on the number of babies born before 37 weeks was unclear (2 studies, 242 women). For women whose waters had broken, it is unclear whether healthcare provider knowledge makes any difference to whether the women gave birth preterm, or on the number of infections, again because we judged the quality of evidence as very low. For women with singleton pregnancies not showing symptoms of preterm birth, it is unclear whether an ultrasound to measure cervical length made any difference to whether their babies were born before 37 weeks' gestation (1 study, 296 women; very low-quality evidence). What does this mean? We found a limited number of studies including small numbers of women. The studies varied in their design and had a broad spread of results. Women were not blinded to whether they had an ultrasound or not. Currently, there is not enough high quality research to show if knowledge of cervical length in women with twin or singleton pregnancies has any effect. Future studies could include ways of managing women as a result of the cervical length results, and it would be useful to look at specific populations separately, such as single babies versus twins and women with and without symptoms of preterm labour. They could also report on all important maternal and perinatal outcomes, and include cost-effectiveness analyses.
This updated review assessed whether there were harmful or beneficial effects from participating in randomized controlled trials (RCTs). The outcomes of patients who participated in RCTs were compared with outcomes of patients who were eligible for the trial and received similar clinical interventions, but did not participate. Comparisons were included both of 'experimental' treatment inside and outside of RCT and of 'control' treatment comparisons. On average, the outcomes of patients participating and not participating in RCTs were similar, suggesting that participation in RCTs, independent of the effects of the clinical interventions being compared, is likely to be comparable.
Fifteen trials involving a total of 2064 participants were included. Three types of photocoagulation were used in the trials: direct photocoagulation of the entire CNV, perifoveal photocoagulation and grid photocoagulation. Control groups in the trials included observation only, submacular surgery and different lasers. This review found that the use of photocoagulation is effective for people with lesions that are outside the centre of the macula. However, these types of lesions are less common in AMD. Severe loss of vision can be prevented in about one in six people.
This review of existing studies was carried out by the Cochrane Oral Health Group and the evidence is current up to 13 May 2013. In this updated review there are now 22 trials published between 1975 and 2012 in which a total of 12,455 children were randomised to treatment with either fluoride varnish or placebo/no treatment. Study duration ranged from one to five years among included trials (12 of these lasted two years). The evidence produced has been found to be of moderate quality due to issues with trial designs. However in the 13 trials that looked at children and adolescents with permanent teeth the review found that the young people treated with fluoride varnish experienced on average a 43% reduction in decayed, missing and filled tooth surfaces. In the 10 trials looking at the effect of fluoride varnish on first or baby teeth the evidence suggests a 37% reduction in decayed, missing and filled tooth surfaces. There was little information concerning possible adverse effects or acceptability of treatment. The evidence presented is of moderate quality due to issues with trial designs.
The review authors searched the medical literature in order to clarify the role of PEI and PAI for the treatment of liver cancer and to compare their benefits and harms with no treatment, with placebo (a pretend treatment), or with other treatments (such as laser, cryoablation, or microwave ablation; hepatic resection; and liver transplantation). We collected and analysed data from randomised clinical trials (where people were allocated at random to one of two or more treatments groups) of people with liver cancer who were able to receive PEI or PAI. Evidence is current to July 2014. The review authors only identified three randomised trials with 261 participants. The risk of bias was low in one and high in two trials. We found two trials that compared PEI versus PAI and one trial that compared PEI versus surgery. We found no trials that compared PEI or PAI versus sham (pretend) intervention, best supportive care, cryotherapy, laser-induced thermotherapy, or high-frequency ultrasound. We found no randomised trials that compared PAI versus surgery. The review authors found low-quality evidence suggesting that PEI yielded the same result as PAI regarding overall survival (the length of time that the person remains alive) and recurrence-free survival (time that the person remains free of cancer). We calculated the number of participants that would be required to judge a relative risk reduction (relative risk is a comparison of the risk of an event happening for one treatment group compared with another treatment group) for survival of 20%. We found that for the comparisons PEI versus PAI, the number of participants was too low to reach valid conclusions. In both groups, participants reported the occurrence of mild side effects such as transient fever, flushing, and local pain. Based on one randomised trial with high risk of bias, there was very low quality evidence that surgical resection does not seem to be superior to PEI in people with early liver cancer. Of note, no severe side effects occurred in people treated with PEI while there were three postoperative deaths in people treated surgically. Again, too few participants were randomised to claim or reject important differences. There is a need for more randomised clinical trials assessing interventions for people with early-stage liver cancer. Such trials should be conducted with low risks of bias (systematic errors, that is overestimation of benefits and underestimation of harms) and of play of chance (random errors, that is errors due to too few participants and too few outcomes).
Through February 2013, we did computer searches for randomized controlled trials of the skin patch or vaginal ring compared to pills for birth control. Pills included types with both estrogen and progestin. We wrote to researchers to find other trials. We found 18 trials. Of six patch trials, five compared the marketed patch to birth control pills and one studied a patch being developed. Of 12 ring trials, 11 looked at the marketed ring and pills while one studied a ring being developed. The methods compared had similar pregnancy rates. Patch users reported using their method more consistently than the pill group did. Only half of the patch studies had data on pregnancy or whether the women used the method correctly. However, most of the ring studies had those data. Patch users were more likely than pill users to drop out early from the trial. Ring users were not more likely to drop out early. Compared to pill users, users of the marketed patch had more breast discomfort, painful periods, nausea, and vomiting. Ring users had more vaginal irritation and discharge than pill users but less nausea, acne, irritability, depression, and emotional changes. Ring users often had fewer bleeding problems than pill users. The quality of information was classed as low for the patch trials and moderate for the ring studies. Lower quality was due to not reporting how groups were assigned or not having good outcome measures. Other issues were high losses and taking assigned women out of the analysis. Studies of the patch and ring should provide more detail on whether women used the method correctly.
This review of 33 small studies (2267 participants) evaluated fusion techniques used to treat degenerative disc disease. The major treatments were discectomy (removal of the damaged disc) alone, addition of a fusion procedure (bone transplanted from another part of the body, cement, or cage), and addition of a plate. None of the evidence from this systematic review indicates that one technique is better than another for clinically significant pain relief for patients with chronic cervical degenerative disc disease or disc herniation. The choice for a specific technique cannot be made on the most important aspect, pain relief, which was the primary outcome parameter in our review. There is moderate quality evidence that there was little or no difference in Odom’s criteria (a tool that measures the success of the surgery at relieving the symptoms that were troublesome prior to the surgery) between those who received a bone transplant from the hip and a metal cage to help with fusion. There is moderate quality evidence that the use of a bone graft (bone transplanted from another part of the body) is more effective than discectomy alone in achieving fusion. There is low quality evidence that transplanting bone from the iliac crest is more effective in achieving fusion than using a cage, while cages are more effective in preventing complications. Further research is very likely to have an important impact on the results and our confidence in them.
We included research published up until August 2018. We found three relevant studies involving 1879 participants. These studies were reported from three countries. Participants were over 65 years of age with three or more long-term health problems on average. Interventions investigated included: · patient workshops and individual patient coaching; · patient coaching including cognitive-behavioural therapy; and · whole-person patient review, practitioner training, and organisational changes. All studies were funded by national research bodies. None of the studies reported the main outcome ‘patient involvement in decision-making about their health care’ nor whether there was less patient involvement as a result of the intervention. Interventions were not found to increase adverse outcomes such as death, anxiety, emergency department attendance, or hospital admissions.. We are uncertain whether interventions for involving older people with more than one long-term health problem in decision-making about their health care can improve their self-rated health or healthcare engagement, or make any difference in self-efficacy (one's belief in one's ability to succeed in specific situations) or in the overall number of general practice visits. We can report that these interventions probably make little or no difference in patients' quality of life but probably increase the number of patients discussing their priorities, and are associated with more patient consultations with nurses, when compared to usual care. Interventions may be associated with more changes in the management of health conditions when considered from the patient’s perspective when compared with a control group. The quality of the evidence was limited by small studies, and by studies choosing to measure different outcomes, resulting in lack of data that could be combined in analyses. Further research in this developing area is required before firm conclusions can be drawn.
We identified 15 randomised trials meeting the review inclusion criteria. These include 14 trials reporting data from 2894 women; one trial reported data from 969 cycles so could not be included in meta-analysis. All of the included studies were parallel-design randomised controlled trials conducted in Brazil, Chile, Singapore, Argentina, Finland, Turkey, Spain, Israel, Canada, Greece, Japan, Italy, Norway and Belgium. The evidence is current to April 2016. Only three of 15 studies reported on live birth as an outcome. We found that there was no clear evidence of a difference between Day three and Day two embryo transfer for rates of live birth, ongoing pregnancy, clinical pregnancy, multiple pregnancy or miscarriage. There were no data reported for complication rate, fetal abnormality or women's evaluation of the procedure. Allocation concealment was poorly reported in the included studies and blinding was not possible (although we feel this is unlikely to affect pregnancy outcomes). Blinding of outcome assessors was not reported. The quality of the evidence ranged from moderate to very low. The main reasons for downgrading the evidence were poor reporting of study methods (risk of bias), lack of agreement between studies (inconsistency), low event rates and lack of accuracy (imprecision) for some outcomes and poor reporting of live birth outcomes (selective reporting). Any further studies comparing these timings of embryo transfer are unlikely to alter the findings and we do not plan to update this review again. Many of the trials included in this review have used outdated techniques that include stimulation, laboratory technology and transferring more than one embryo. We would direct the reader to the Glujovsky 2016 Cochrane review comparing Day 2/3 with day 5/6 embryo transfer.
We identified 22 trials with a total of 9137 participants to include in this review (current until May 2016). The mean age of participants, where reported, was 65.2 years. Most participants had either a high-risk procedure or condition. The predisposing conditions were orthopedic surgery in 12 studies and urology, cardiothoracic, neurosurgery, trauma, general surgery, gynaecology or other types of participants in the remaining studies. Compared to IPC alone, IPC plus medication did not show differences in the incidence (rate of new cases) of PE (12 studies with a total of 3017 participants). The incidence of DVT was reduced for IPC combined with medication when compared with IPC alone (11 studies with a total of 2934 participants). The addition of a medication to IPC, however, increased the risk for any bleeding compared to IPC alone, from 0.66% to 4.0%. Major bleeding followed a similar pattern, with an increase from 0.1% to 1.5%.Further analysis looking at different subgroups of participants (orthopedic and non-orthopedic participants) did not show any overall difference in DVT while it was not possible to assess differences between subgroups for PE. Compared with medication alone, combined IPC and medication reduced the incidence of PE (10 studies with 3544 participants). DVT incidence was not different between the medication and the combined IPC and medication group (11 studies with 2866 participants). No differences were observed in rates of bleeding (three studies with 244 participants). Further analysis looking at different subgroups of participants did not show any overall difference in incidence of PE and DVT between orthopedic and non-orthopedic participants. The findings of this review show moderate quality evidence and agree with current guideline recommendations supporting the use of combined IPC and pharmacological prophylaxis, compared with IPC or pharmacological prophylaxis alone, to reduce the incidence of DVT and PE in hospitalized patients. Moderate quality evidence suggests the addition of pharmacological prophylaxis to IPC, increased the risk of bleeding compared to IPC alone, a side effect not observed for IPC when added to pharmacological prophylaxis (very low quality evidence), as expected for a physical method for preventing blood clots. The quality of the evidence was downgraded from high to moderate or very low for risk of bias and imprecision and indirectness between the studies.
We looked for trials which compared SPT to usual care or to another treatment. Ideally, people with dementia should have been randomly allocated to one or other treatment, but we also included trials even if treatment allocation was not strictly random. We found three trials which met our inclusion criteria. The 144 participants were all living in nursing homes. The majority were women with an average age of over 80 years and severe dementia. The way SPT was administered was different in each trial. All the trials used more than one comparison treatment, which differed between trials. The trials all attempted to measure an effect on agitated behaviours, but used different approaches. Because the trials were so different from each other, we were not able to pool the results. Individually, each trial reported different methods to assess the effect of SPT on behavioural problems and the results varied depending on the method used to measure the outcome. None of the studies assessed quality of life, effect on daily activities, effects on caregivers, or how likely participants were to drop out of the study. The studies were small and all had problems with their methods which could have biased their results. Hence, we thought the overall quality of the evidence was very low, meaning we cannot be at all confident in the results. Not enough high-quality research has been done to allow us to judge whether SPT can help people with dementia who are distressed or agitated.
Some studies assessed buying food or drinks from vending machines, grocery stores, restaurants, cafeterias, or coffee shops. Others assessed the amount of food or drink consumed during a snack or meal in an artificial setting or scenario (referred to as laboratory studies or settings). What are the main results of the review? Nutritional labelling on restaurant menus reduced the amount of energy (i.e. calories) purchased, but the quality of the three studies that contributed to this finding was low, so our confidence in the effect estimate is limited and may change with further studies. Eight studies assessed this same type of intervention in laboratory settings, but instead of evaluating how much energy participants purchased, these studies evaluated how much energy participants consumed. These studies did not conclusively demonstrate a reduction in energy consumed when menus or foods were labelled, and they were also of low quality. In addition, six laboratory studies assessed how much energy participants consumed when they were given one food or drink option with or without labels, and five laboratory studies assessed how much energy participants consumed when foods were experimentally labelled as low energy or low fat when they were actually high-energy foods (i.e. mislabelling). Results from these two groups of studies were inconclusive and of low, or in the case of mislabelling studies, very low quality. We found some studies that assessed labelling on vending machines and grocery stores, but their results were not easy to interpret, so we could not use them to inform this review. How up-to-date is this review? The evidence is current to 26 April 2017.
The evidence is current up to 13 June 2014. We found 20 relevant randomized controlled trials with 1401 participants undergoing surgical procedures with general anaesthesia. These studies compared an α-2 agonist (either clonidine or dexmedetomidine) with a control. The doses, methods, and time that the drugs were given varied between studies. All studies reported results for shivering. Our analysis showed that α-2 agonists significantly reduce the risk of postoperative shivering when administered before or during surgery. However, our analysis also showed that there were significant differences between studies that we could not explain. Some study authors had also presented results for core temperature, length of stay in the recovery room, and clinical side effects of the drugs. Seven studies reported that participants given dexmedetomidine were more likely to have a higher level of sedation after surgery, and five studies reported that participants given dexmedetomidine were more likely to have bradycardia (slower heart rate). We did not combine these results in an analysis. None of the studies presented patient-reported outcomes. We felt that the quality of the evidence was low and that some authors did not make enough of an effort to reduce the risk of bias in the methods, which could affect their results. For example, not all authors masked the anaesthetist or surgeon to which drug was given to each participant. This, along with some unexplained differences between studies and some concern about whether we could have missed some relevant results that had not been published, led us to assess the quality of the evidence for shivering as very low. We used GRADEpro software to assess evidence quality. Alpha-2 agonists may reduce the number of people who shiver after surgical procedures, but they are likely to make people sleepier as a side effect. However, the evidence is from studies of very low quality.
Four randomized controlled studies were included in the review; individual studies suggest that educational and counselling interventions may encourage women to abstain from alcohol or reduce the amount of alcohol they drink in pregnancy. The studies involved women who were less than 28 weeks pregnant who were consuming some alcohol. All were carried out in the USA. The interventions ranged from a 10-minute education session and provision of a self-help manual through to an hour-long motivational interview with reinforcement at each prenatal visit. Women in the control groups generally received routine care, which may have included advice on reducing alcohol intake. Outcomes were measured in different ways, and so results have been presented separately for each study. The studies provided very limited information on the effects of interventions on the health of women and their babies. There was very little information provided in these studies on the effects of interventions on the health of mothers and babies. There is an urgent need for more information in this area.
We carried out a wide search for studies of treatments to prevent this type of nerve damage. We identified a total of 29 clinical trials, which involved almost 3000 participants who were receiving platinum-containing anticancer drugs (mostly cisplatin, oxaliplatin and carboplatin) for various types of cancer (mainly colon, ovary, and lung cancers). The nine treatments studied were: amifostine (seven trials), calcium and magnesium (four trials), glutathione (seven trials), Org 2766 (four trials) and vitamin E (three trials). There was one trial each of acetylcysteine, diethyldithiocarbamate (DDTC), oxcarbazepine, and retinoic acid. We chose an objective clinical test of sensation to report as our preferred measure of the effects of treatment. Only seven of the studies used this measure. Nine reported the results of nerve conduction studies which are another objective measure of nerve function. Most of the studies used a subjective assessment of neuropathy, such as the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy grading scale. Most of the included studies were fairly well performed, where it was possible to obtain this information. Based on the combined results that generally described secondary and non-quantitative measures such as the NCI-CTC neuropathy grading scale, modest but promising (borderline statistically significant) results favoured the use of amifostine, calcium and magnesium, and glutathione to reduce the neurotoxicity of cisplatin and related chemotherapies. Three studies of vitamin E could only be studied individually but the results of each imply some mild subjective benefits. Nevertheless, given the limitations of the studies, such as small numbers of participants, lack of objective measures of neuropathy, and differing results among similar trials, the data remain insufficient to conclude that any of the neuroprotective agents tested prevent or limit the neurotoxicity of platinum drugs. Most of the treatments were not associated with adverse events. Amifostine infusions were associated with temporary low blood pressure in a significant number of cases, and retinoic acid with low levels of calcium in the blood. About one-fifth of people treated with DDTC stopped taking it because of harmful effects. Amifostine, calcium and magnesium, vitamin E, and glutathione require further well designed trials to clarify if they are effective or not. This is an updated review. The evidence is current to 4 March 2013.
This review comprises published research studies current through June 2014. A total of 10 randomised controlled trials (RCTs), or studies comparing one treatment to another, were included in the final analysis. In total, the included studies looked at 733 participants. In this review, review authors compared conventional laminectomy versus three other surgical techniques for low back stenosis. Here's the breakdown: Three studies - involving a total of 173 patients - compared conventional laminectomy with one-sided laminotomy. Four studies - involving 382 patients total - compared conventional laminectomy with two-sided laminotomy (one study included three treatment groups and compared conventional laminectomy with one-sided and two-sided laminotomy). And finally, four studies - involving 218 patients total - compared conventional laminectomy with a split-spinous process laminotomy. The Cochrane review authors did not receive outside funding. This review found that each of the three newer techniques of surgery for low back stenosis delivered results no different from those of conventional laminectomy regarding self-care abilities and leg pain. Only perceived recovery of symptoms favoured patients who underwent bilateral laminotomy compared with conventional laminectomy, but the difference between unilateral laminotomy and split-spinous process laminotomy was not significant. The quality of evidence was low or very low according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) recommendations. This was due to the limited number of studies available for review and to poor study designs. Included studies were not designed in such a way as to yield reliable information about surgical outcomes. Before high-quality, evidence-based recommendations can be made about techniques of decompression for lumbar spinal stenosis, more rigorous studies should be done.
However, this review is part of a series of reviews looking at drugs to help relieve perineal pain once it is there in the early days after the birth. This review identified 10 studies, involving 1367 women, looking at how effective paracetamol might be in helping with this pain. The studies were quite old and thus not of high quality. However, they showed that paracetamol (either in a single 500 mg to 600 mg or a single 1000 mg dose) was effective at reducing the perineal pain, mostly caused by episiotomies. The studies did not look carefully at potential adverse effects but generally paracetamol at these doses causes few problems. There are also generally no identified problems for breastfed babies when mothers take paracetamol, but these outcomes were not specifically assessed in any of the included studies. The comparison of how effective paracetamol is compared with other drugs is being assessed in the other reviews in the series.
In February 2016 we searched the medical literature for studies examining the effectiveness of breastfeeding babies 1 to 12 months old during the use of needles. We compared effectiveness of breastfeeding in reducing pain (as scored by crying time and pain scores), to holding, babies lying flat, or the giving of water or sweet solutions. We found 10 studies with a total of 1066 infants. All studies examined if breastfeeding reduced pain during vaccinations. Breastfeeding reduced crying in young babies having vaccinations. On average, breastfed babies cried for 38 seconds less than babies who were not breastfed (6 studies; 547 infants; moderate-quality evidence), and pain scores were significantly lower (5 studies; 310 infants; moderate-quality evidence). No studies reported on any harm (very low-quality evidence). We could draw no conclusions on risk of harm while breastfeeding healthy babies during vaccination. Going forward: if mothers are breastfeeding, it could be considered when possible for babies during vaccinations. More evidence is needed to learn if breastfeeding helps older babies and babies in hospital during blood work or procedures such as insertion of drips. The quality of the evidence was moderate for crying time and pain scores. Most studies included younger infants aged 1 to 6 months. Further research including older infants up to 12 months of age may change our conclusions. In addition, the studies evaluated the effects of breastfeeding during vaccination. We do not know whether breastfeeding helps sick babies aged 1 to 12 months in hospital during blood sampling or drip insertion.
We included 18 trials with 421 participants and 3817 endoscopy procedures. Ten trials compared virtual reality training with no training; five compared virtual reality training with patient-based endoscopy training; one compared virtual reality training with another form of endoscopy simulation training; and two compared two different methods of virtual reality training. Ten trials studied colonoscopy, three studied sigmoidoscopy, and five studied oesophagogastroduodenoscopy. Participants included medical trainees with limited or no endoscopy training from gastroenterology, medicine, family medicine, or general surgery, along with nurses. Compared to no training, virtual reality training appears to provide trainees with an advantage as measured by the ability to complete procedures independently, overall rating of performance, and visualisation of the colon or oesophagus. We found no conclusive evidence that virtual reality training, as compared with traditional patient-based training or another method of endoscopy simulation training, provided benefit, although data were limited. Existing virtual reality simulation curricula can be improved by applying educational theory such as a progressive learning strategy, whereby trainees complete increasingly difficult cases. The results of this review have shown that virtual reality endoscopy training can be used to supplement early traditional endoscopy training for trainees with limited or no endoscopic experience. Overall, the quality of the evidence was poor based on potential bias due to poor methodological reporting in trials and imprecision due to few participants and endoscopic procedures. Future studies must adhere to quality standards, such as proper randomisation, along with using valid metrics to measure endoscopic performance. Researchers should also compare the effectiveness of different simulation curricula that are based on educational theories.
This review compared the effects of amisulpride with those of other so called second generation (atypical) antipsychotic drugs. For half of the possible comparisons not a single relevant study could be identified. Based on very limited data there was no difference in efficacy comparing amisulpride with olanzapine and risperidone, but a certain advantage compared with ziprasidone. Amisulpride was associated with less weight gain than risperidone and olanzapine.
This review identified three randomised controlled trials in the area of psychological treatments for anxiety after TBI. Some evidence was found for the effectiveness of the following interventions: cognitive behavioural therapy (CBT) for treatment of acute stress disorder following mild TBI, and combining CBT and neurorehabilitation for treatment of general anxiety symptoms in people with mild to moderate TBI. The ability to make strong conclusions on the effectiveness of these approaches is limited by the small number of trials available for pooling of data, especially trials with similar conditions and participants.
A literature search was conducted identifying 30 potential trials; four trials were excluded. The 26 clinical trials included in this review encompass a large range of different drugs, doses and combinations in a mixed group of patients over a long time period (1976 to 2011), making it difficult to compare treatment options. Although there are no trials directly comparing chemotherapy with symptomatic management alone, chemotherapy is widely used in this setting and assumed to be of benefit. Cisplatin and carboplatin chemotherapy were shown to shrink the cancer in 10% to 30% of patients and are widely used in current practice. Cisplatin chemotherapy when combined with other drugs has been shown to prolong survival by a few months compared with cisplatin alone, but with the cost of increased side effects. Other chemotherapy has been used, but has been found to be less effective or more toxic. Quality of life for patients on chemotherapy appears to be similar for cisplatin and cisplatin-based combinations. Nearly all patients in these studies were relatively fit and well prior to starting treatment, despite their cancer; these results may not be the same in patients who are not fit and well.
The current review planned to examine studies on the use of melatonin in these children to determine whether this drug is effective for improving their sleep (safety is not mentioned in objectives or abstract and adverse effects is a secondary outcome). We only wanted to use studies where the children had been randomly allocated to a treatment group and a control group that got no treatment or another medication or a placebo. We did not find any of these studies that were suitable to be included in our review and so we are unable to draw any conclusions about whether or not melatonin improves sleep for visually impaired children. To find out, we need appropriately designed clinical trials. Due to lack of knowledge about best practice in the use of melatonin with these children, it would be useful to have researchers involved who are experienced in sleep disorders and in evidence-based practice research. In addition, studies involving more than one location would be beneficial to increase the number of children being evaluated and make it more likely we will reach solid conclusions about whether melatonin works for this group of children, as well as details about the most effective dosage and timing of the treatment.
This is an update of the original review published in 2010. We performed a new search and found 10 new studies (with 4227 participants) to add to the original review, which changed some of the findings. In total, we found 28 randomised trials including 8950 participants that compared self-monitoring and self-management with standard monitoring. The quality of the evidence was generally low to moderate. The combined results of the 28 trials showed a halving of thromboembolic events with self-monitoring and self-management and no reduction in the number of major bleeds. Self-management had similar reductions in thromboembolic events and mortality to the overall benefit, with no effect on major bleeds. Self-monitoring halved the number of major haemorrhages that occurred but did not significantly reduce the rates of thrombotic events or all-cause mortality. In conclusion, self-monitoring or self-management can improve the quality of oral anticoagulant therapy, leading to fewer thromboembolic events and lower mortality, without a reduction in the number of major bleeds. Self-monitoring and self-management are not feasible for all patients, which requires the identification and education of suitable patients.
This review includes 17 studies (from 54 reports) with 23,200 children. Four of the included studies were conducted in Malawi, three in Bangladesh, two in Ghana and one each in Burkina Faso, Haiti, Honduras, Chad, Congo, Kenya, Niger, Peru, Guatemala, and Indonesia. Four included studies enrolled pregnant women and provided LNS plus complementary feeding during pregnancy and post-partum, followed by infant supplementation starting at six months of age. The other studies provided LNS plus complementary feeding to children after six months of age. None of the included studies were conducted in emergency settings. Findings of this review suggest that LNS plus complementary feeding is probably an effective intervention for improving growth outcomes and reducing the occurrence of children who are of short stature for their age (stunting), have low weight for their age (moderate underweight), have low weight for their height (moderate wasting) and anaemia. Additionally, LNS plus complementary feeding probably improves height and weight for age as well as mid-upper arm circumference without adverse effects among children aged six to 23 months. The intervention seems to be more effective if provided for a duration longer than 12 months. Evidence also suggests that LNS plus complementary probably reduces moderate stunting, moderate wasting and moderate underweight, compared to other FBF. Furthermore, LNS plus complementary feeding is probably more effective than MNP at reducing moderate underweight and improving height and weight. Overall, we considered most studies to be at high risk of bias for blinding of participants and personnel due to the nature of intervention. We rated the quality of the evidence for most outcomes as either low or moderate. The evidence is current to October 2018.
This review of studies of vitamin E supplements found that while extra vitamin E reduces the chances of some complications (including disease of the retina), the risk of life-threatening infection is increased. The risk of bleeding in the brain is increased when extra vitamin E is given by vein but decreased when the extra vitamin E is given by other routes.
Evidence from this updated review, which includes eight trials involving 5701 participants, indicates that there is currently not sufficient evidence to support the routine use of fibrinogen depleting agents for the treatment of acute ischaemic stroke. Further trials are needed to determine reliably whether there is worthwhile benefit, and if so, which categories of patients are most likely to benefit.
We searched for evidence on 20 May 2019 and identified 11 randomised studies (studies in which participants are assigned to one of two or more treatment groups using a random method) that enrolled a total of 2412 women. Nine studies tested NRT used alongside counselling to stop smoking, whilst the other two studies tested bupropion. Low-quality evidence suggests that NRT combined with behavioural support might help women to stop smoking in later pregnancy more than behavioural support alone. Medication trials often use placebos, that is tablets or patches that look like the drug but do not actually include it, so that each comparison group has equal expectation of success and there is a fairer test of the benefits of the medicine itself. When just the higher-quality, placebo-controlled trials were analysed, the evidence suggested that NRT was more effective than placebo NRT. There was no evidence that either nicotine patches or fast-acting NRT (such as gum or lozenge) was more effective than the other. Low-quality evidence suggests that bupropion may be no more effective than placebo in helping women quit smoking later in pregnancy. We found no trials investigating other smoking cessation pharmacotherapies or electronic cigarettes. There was insufficient evidence to conclude whether NRT had either positive or negative impacts on rates of miscarriage, stillbirth, preterm birth (less than 37 weeks), mean birthweight, low birthweight (less than 2500 g), admissions of babies to neonatal intensive care, or newborn deaths. However, in one trial where infants were followed until two years of age, those infants born to women who had been randomised to NRT were more likely to have healthy development. Similarly, it is unclear whether bupropion had a positive or negative impact on birth outcomes. Studies that looked at whether women used their stop smoking medications as instructed found that use was generally low, and the majority of women used little of the NRT they were given. More research evidence is needed, in particular placebo-controlled trials that test higher doses of NRT, encourage women to use sufficient medication, and follow infants into childhood. Furthermore, more studies are required investigating the effect and safety of bupropion, electronic cigarettes, and varenicline for giving up smoking during pregnancy.
We sought evidence for the usefulness of these video-assisted devices for the placement of breathing tubes in babies. We searched scientific databases for clinical trials of babies who needed intubation in the delivery room, operating room or intensive care unit. The studies could measure time to intubation, number of attempts at intubation, success rate of first intubation or side effects. The evidence is current to May 2017. We included three studies, which provided data on up to 467 intubation attempts in newborns by trainees. Data from three included studies suggest that videolaryngoscopy increases the success of intubation at first attempt but does not decrease the time to intubation, the number of attempts or side effects due to placement of the breathing tube. These studies were done with trainees and highlights the use of videolaryngoscopy as a teaching tool. We make a case for further research in evaluating the use of video-assisted devices in the placement of breathing tubes in newborns.
We performed a systematic search of the literature to identify all the randomised controlled trials conducted on this topic. A total of 232 patients in four trials were randomised to remote ischaemic preconditioning or no preconditioning for three different operations on blood vessels. Based on the evidence from these small trials, there were too few data to be able to say whether remote ischaemic preconditioning has any beneficial or harmful effects. The studies varied in the surgical procedures, outcome measures and the way remote ischaemia was induced. The number of deaths around the time of surgery was not clearly different between the two groups. Heart attacks (myocardial infarction) may have been reduced in the remote ischaemic preconditioning group but this was apparent in only one trial and was not consistent across the trials. Unplanned critical care admissions tended to increase in the remote ischaemic preconditioning group. All the trials had a high risk of bias and the safety of this technique needs to be confirmed in trials with adequate numbers of participants.
This review included 13 trials with 5810 participants from Latin America, Africa and Asia. All trials compared the provision of MNP for point-of-use fortification with no intervention or placebo. Six trials included participants younger than 59 months of age only, four included only children aged 60 months of age or older, and three trials included children both younger and older than 59 months of age. MNPs contained from two to 18 vitamins and minerals. We searched existing clinical trials in December 2016 and ongoing trials in April 2017. We also contacted relevant institutions for additional information upon publication of the protocol and in April 2017. The review found that children receiving iron-containing MNP for point-of-use fortification of foods were at significantly lower risk of having anaemia and iron deficiency and had higher haemoglobin concentrations. We did not find any positive or negative effect on diarrhoea or mortality, but the data on these two outcomes were very limited. We rated the overall quality of the evidence for the provision of multiple MNP versus no intervention or placebo as moderate for anaemia, iron deficiency and adverse effects. We judged the evidence to be of low quality for haemoglobin, mortality and diarrhoea, and to be very low-quality for ferritin. In general, the most common risk of bias in the studies was the lack of blinding for participants, personnel and outcome assessors. Point-of-use fortification of foods with MNPs containing iron reduces anaemia and iron deficiency in preschool- and school-age children and seems feasible for public health purposes. However, future research should aim to increase the body of evidence on mortality, morbidity, developmental outcomes and adverse effects. Due to the lack of trials, we were unable to determine at this time if this intervention has comparable effects to those observed with iron supplements (provided as drops, tablets or syrup).
We included six randomised studies (involving 122 pregnant women) but only four studies (involving 116 women) contributed to the analyses. Our review found that there is not enough reliable evidence to compare planned caesarean delivery with planned vaginal delivery. Sometimes a planned caesarean cannot happen because labour progresses too quickly and sometimes, even though vaginal delivery is planned, complications arising during labour may make a caesarean section necessary. The review found that not enough women have been recruited into trials and, therefore, the decision how best to deliver a preterm baby, either cephalic or breech presentation, remains opinion and current practice within a hospital, rather than being evidence-based. All four trials were stopped early, due to difficulties with recruiting women. There were no data on serious maternal complications including admissions to intensive care unit. However, there were seven cases of major maternal postpartum complications in the group allocated to planned caesarean section (wound dehiscence, deep vein thrombosis, endotoxic shock and puerperal sepsis) and none in the group randomised to vaginal delivery. Excess blood loss from the birth canal after childbirth (postpartum haemorrhage) was not clearly different between the two groups, nor was birth asphyxia or respiratory distress syndrome or injury to the baby at birth.
We searched the literature to May 2016 and found three published randomised trials that met the review inclusion criteria. We did not identify any ongoing trials. The three included studies involved 708 participants who had undergone excisional treatment to the cervix (known as laser or large loop excision of transformation zone (LLETZ) or loop electrosurgical excision procedure (LEEP)). Two studies tested a antimicrobial vaginal pessary versus no treatment; the other tested oral antibiotics compared with placebo. We found that there was no benefit to prophylactic antibiotics after LLETZ to reduce or prevent prolonged vaginal discharge, severe vaginal bleeding, fever, lower abdominal pain, unscheduled medical consultation, and additional self-medication. There was little information on antibiotic-related adverse effects. The limited evidence available does not support routinely giving antibiotics for infection prevention after LLETZ. As there are growing concerns with antibiotic resistance, antibiotics for infection prevention after excision of the cervical transformation zones should only be used in the context of clinical trials. The quality of the evidence regarding prophylactic antibiotics for preventing severe vaginal bleeding, fever, and adverse events was very low, with evidence from other comparisons being of low quality.
The review looked for randomised studies to assess the impact of dieting or exercise, or both, on women's weight loss in the months after giving birth. It paid particular attention to breastfeeding women to be sure that breastfeeding was not compromised. The review of trials found 14 studies, with 12 studies involving 910 women carrying excess weight after childbirth that contributed data for analysis. The findings suggest that diet combined with exercise or diet alone compared with usual care seemed to help with weight loss after giving birth. There is potential for these interventions to play a role in preventing future maternal obesity. There was not sufficient evidence to be sure that exercise or diet did not interfere with breastfeeding though it appeared not to in the included studies. It seems preferable to lose weight through a combination of dieting and exercise, compared to dieting alone, because exercise is thought to improve circulation and heart fitness, and to preserve lean body mass. Further research is needed.
In our review, we looked at 27 randomized controlled trials of drugs compared to placebo to find out which treatments were effective at providing pain freedom two hours after treatment. We also wanted to know what side effects might be caused by the treatments. A total of 7630 children received medication in the studies. The evidence is current to February 2016. Each study had between 13 and 888 participants. Their average age was 12.9 years and ranged from 8.2 to 14.7 years. Nineteen of the studies were funded by the drug manufacturer. Ibuprofen appears to be effective in treating children with migraine, but the evidence is limited to only two small trials. Ibuprofen is readily available and inexpensive, making it an excellent first choice for migraine treatment. Paracetamol was not shown to be effective in providing pain freedom in children, but we only found one small study. Triptans are a type of medication designed specifically to treat migraine and are often effective at providing greater pain freedom in children and adolescents. The triptans examined in children included rizatriptan and sumatriptan, while almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan were examined in adolescents. The combination of sumatriptan plus naproxen sodium is also effective at treating adolescents with migraine. Overall, there is a risk that the triptan medications may cause minor unwanted side effects like taste disturbance, nasal symptoms, dizziness, fatigue, low energy, nausea, or vomiting. The studies did not report any serious side effects. The overall quality of the evidence provided by the review was moderate for the triptans, but low for paracetamol and ibuprofen, as we only identified a few studies. More studies need to look at the effects of each of the migraine treatments in children and adolescents separately.
This review aimed to find out if there were important differences between different clot-dissolving drugs. It also aimed to find out if there were differences in effect when giving the same drug in different doses or by different routes (into an artery or a vein). The review, which included 20 studies involving 2527 participants, showed that there was some evidence that lower doses of thrombolytic agents led to serious bleeding in the brain less often. However, it was not clear if the benefit from lower doses was as big as with higher doses. There was no evidence to show that one thrombolytic agent was clearly better than another, or that intra-arterial treatment was better than intravenous treatment. Therefore, more larger randomised controlled trials are required to answer questions about which drug, or dose or route of administration is best for thrombolysis. At present, rt-PA as currently licensed in many countries, should be regarded as best practice.
We searched for all randomised controlled trials comparing psychological therapies to a control, other psychological therapies or other therapies for the treatment of PTSD in children and adolescents aged 3 to 18 years. We identified 14 studies with a total of 758 participants. The types of trauma related to the PTSD were sexual abuse, civil violence, natural disaster, domestic violence and motor vehicle accidents. Most participants were clients of a trauma-related support service. The psychological therapies used in the included studies were cognitive behavioural therapy (CBT), exposure-based, psychodynamic, narrative, supportive counselling, and eye movement desensitisation and reprocessing (EMDR). Most included studies compared a psychological therapy to a control group. No study compared psychological therapies to medications or medications in combination with a psychological therapy. There was fair evidence for the effectiveness of psychological therapies, particularly CBT, for the treatment of PTSD in children and adolescents for up to a month following treatment. More evidence is required for the effectiveness of psychological therapies in the longer term and to be able to compare the effectiveness of one psychological therapy to another. The findings of this review are limited by the potential for bias in the included studies, possible differences between studies which could not be identified, the small number of identified studies and the low number of participants in most studies.
This review included 47 studies with 2884 participants. The average age of the children and adolescents was 12.6 years. Most studies included young people with headache (23 studies) or stomach pain (10 studies), The remaining studies investigated children with irritable bowel syndrome, fibromyalgia, temporomandibular disorders, sickle cell disease, inflammatory bowel disease, or included samples with various chronic pain conditions. Psychological therapies reduced pain frequency immediately following treatment for children and adolescents with chronic headache, and pain intensity and anxiety for children and adolescents with other chronic pain conditions. Psychological therapies also reduced disability for children and adolescents with non-headache chronic pain conditions immediately following treatment and for children with headache and mixed chronic pain conditions up to 12 months later. We did not find any benefit of psychological treatments on reducing anxiety for children with headache or for depression in children with headache or mixed chronic pain conditions. We judged all outcomes to be low or very low-quality, meaning our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect or we have very little confidence in the effect estimate; or the true effect is likely to be substantially different from the estimate of effect.
This review found only one randomized trial of treatment for spasticity in motor neuron disease, which involved 25 participants, and no further trials have been found in subsequent updates. There were a number of issues with the design of the study which unfortunately reduced the certainty of the findings. At three months participants performing the 15 minute twice daily exercises had significantly less spasticity overall than control participants (mean reduction of -0.43, 95% confidence interval (CI) -1.03 to +0.17 in the treatment group versus an increase of +0.25, 95% CI -0.46 to +0.96 in control) but the mean change between groups was not significant, as measured by the Ashworth scale (a scale of spasticity, with a range of 0 to 5, where higher is worse). The trial was too small to determine whether individualized moderate intensity endurance type exercises for the trunk and limbs are beneficial or harmful. No side effects from exercise were reported. No other randomized trials of different treatments or therapies were found. Further research is needed to determine if exercise or other therapies such as anti-spasticity medication are beneficial or harmful.
Two trials were included in the review involving a total of 529 people. No recommendations can be made regarding filter efficacy in preventing pulmonary embolism. One trial which was conducted in 1972 showed a reduction in pulmonary embolism rates but not deaths in a group of people who suffered traumatic hip fractures and who had a filter inserted. No preventive DVT treatment was given as this was controversial at the time. Outcomes were given at 34 days.The trial participants were inadequately randomised, had a higher proportion of people who were not able to undergo surgical fixation in the control group, and outcome assessors were not blinded. In the PREPIC trial, caval filters were associated with an increased risk of blood clot formation in the legs following their insertion. This study did not demonstrate any difference in the death rates between the two groups; the participants were older (average age 73 years) with co-existing medical conditions and the majority of people died from cancer-related causes or heart problems. No details were recorded of adverse events of filters, but the numbers in this trial were not of sufficient size to detect them. There is a lack of information on the effectiveness of caval filters in other clinical scenarios, especially in the two situations where they are used most frequently and thought to be the most advantageous. These are when patients cannot be anticoagulated, or when pulmonary embolism occurs despite adequate anticoagulation. Vena caval filter use is increasing and more trials are needed to confirm their benefit and accurately assess their safety.
The review included 35 studies with 1138 people with cystic fibrosis aged between 4 and 63 years of age. Studies compared different physiotherapy treatments and people were selected for one treatment or the other randomly. Not many studies looked at the same types of physiotherapy over the same period of time; studies ranged in duration from two days to 13 months. Given the differences in study design, it was difficult to combine the results from these studies in a useful way. We did not find any clear evidence that vibrating devices were better than any other form of physiotherapy which they were compared to in these studies, or that one device was better than another. One study found that people using an vibrating device needed additional antibiotics for a chest infection more often than those using positive expiratory pressure. When recommending the most suitable method of airway clearance, physiotherapists should consider the needs of the people they are treating. For the future, larger and longer trials are needed to measure the frequency of lung infections, preference, adherence to and general satisfaction with treatment, financial constraints should also be taken into consideration. We think adherence is important, because if people with cystic fibrosis are willing to stick to their physiotherapy regimen, there may be improvements in other outcomes such as exercise tolerance, respiratory function and mortality. Overall, we thought most studies had some design problems which might affect our confidence in some of the results. In about a quarter of studies there were concerns that not all the results were reported clearly and in about a third of the studies the reasons for people withdrawing from a trial were not clearly explained. In comparisons of different types of physiotherapy, a person and their physiotherapist will always know which treatment they are receiving and this might affect their answers to some questions, such as which treatment makes them feel better, but we only thought this was a problem in a few studies. We used a scoring system called GRADE to assess the quality of the evidence, we then judged it to be either low or very low quality, which suggests that further research is very likely to affect our confidence in the results in this review for of any of the interventions analysed.
Decisions about whether to participate in randomized trials are made more difficult because of the widespread belief that new treatments must inevitably be superior to existing (standard) treatments. Indeed, it is understandable that people hope that this will be the case. If this was actually so, however, the ethical precondition of uncertainty would often not apply. This Cochrane methodology review addresses this important question: "What is the likelihood that new treatments being compared to established treatments in randomized trials will be shown to be superior?" Four cohorts of consecutive, publicly funded, randomized trials, which altogether included 743 trials that enrolled 297,744 patients, met our inclusion criteria for this review. We found that, on average, new treatments were very slightly more likely to have favorable results than established treatments, both in terms of the primary outcomes targeted and overall survival. In other words, when new treatments are compared with established treatments in randomized trials we can expect slightly more than half will prove to be better, and slightly less than half will prove to be worse than established treatments. This conclusion applies to publicly funded trials as we did not include studies funded by commercial sponsors in our analysis.The results are consistent with the ethical preconditions for random allocation – when people are enrolled in randomized trials, the results cannot be predicted in advance as there is genuine uncertainty about which of the treatments being compared in randomized trials will prove to be superior.
In February 2013, we searched medical databases to look for controlled trials of participants who had undergone surgery and had been randomly assigned to nurse- or doctor-led preoperative assessment (POA). We found two trials, one randomized and one quasi-randomized. Both studies were conducted in the UK and compared POA performed by the nurse with POA performed by the non-specialist doctor. One studied 1874 adult participants who were undergoing elective surgery, and the other studied 595 children who were undergoing day surgery. Neither study reported on cancellations of surgery, gain in participant information or knowledge or perioperative complications. Reported outcomes focused on the accuracy of the assessment. As there is currently no evidence from trials concerning the impact of nurse-led POA on patient outcomes, we are unable to make any recommendations for practice on the basis of this review.
A total of 26 trials including 6950 patients were included in this review. Fifty-four percent of these patients were female, mean age was 35 years, and mean number of recurrences per year before entry into the trials was 11. Duration of treatment in trials ranged from two to 12 months. A total of 14 trials compared acyclovir versus placebo. Four trials compared valacyclovir versus placebo and two trials compared valacyclovir versus no treatment. Three trials compared famciclovir versus placebo. Two trials compared valacyclovir versus famciclovir, and one trial compared acyclovir versus valacyclovir versus placebo. Among the 26 included trials, 22 declared pharmaceutical company funding. The last search for studies was carried out in February 2014. Suppressive antiviral therapy with acyclovir, valacyclovir, or famciclovir in patients experiencing at least four recurrences per year decreases the number of patients having at least one recurrence compared with placebo. There is no evidence that suggests that any of these drugs is superior to the others. Althought the three antiviral drugs showed better results compared with placebo, we are uncertain as to how much a difference there are likely to make, because of issues with the conduct and reporting of studies, and inconsistency of their results. The quality of the evidence is low and we think that the size of the effects is likely to change with more research. Because few studies compared the three drugs against one other, we are moderately confident in the fact that there is no difference between the three drugs in terms of effectiveness.
This review identified 26 controlled trials looking at the best strategies for removal of catheters. In 11 studies comparing late night versus early morning removal, removal at midnight resulted in a longer time to first void and patients passing significantly larger volumes, although these findings varied widely. There was no apparent effect on the number of patients who required recatheterisation because of subsequent urinary retention, but patients with catheters removed at midnight were discharged from hospital significantly earlier than those with morning removal. Based on findings from 13 trials, limiting how long a catheter was left in place was linked to a shorter stay in hospital and less risk of infection. The information available from three trials was too limited to assess whether clamping prior to removal, to simulate normal filling of the bladder, improved outcomes.
Twenty-three trials involving 2861 older and mainly female patients with hip fractures are included in this review. The findings from the three main comparisons are summarised here. Six studies involving 899 participants compared a press fit arthroplasty with one that was secured in place with bone cement. Those joints that were cemented in place resulted in less pain and better mobility than those that were of the press fit type. Seven trials involving 857 participants compared those implants which have a second joint built into them (bipolar hemiarthroplasties) with those without this additional joint (unipolar hemiarthroplasties). No notable differences between these two types of implant were demonstrated. Seven studies of 734 participants compared different types of hemiarthroplasty with a total hip replacement. Most implants had been cemented in place. There was a trend to better functional outcomes after total hip replacement, but firm conclusions could not be made because of the lack of patient numbers. There is good evidence that people with arthroplasties that are cemented in place have less pain and better mobility after the operation than those, which are inserted as a press fit. There is limited evidence that a total hip replacement leads to better functional outcome than a hemiarthroplasty.
We sought clinical trial evidence from scientific databases to evaluate the effectiveness of these computer systems. The evidence is current to January 2012. We found data from 42 trials (40 randomized controlled trials (trials that allocate people at random to receive one of a number of drugs or procedures) and two non-randomized controlled trials). Computerized advice for drug dosage can benefit people taking certain drugs compared with empiric dosing (where a dose is chosen based on a doctor's observations and experience) without computer assistance. When using the computer system, healthcare professionals prescribed appropriately higher doses of the drugs initially for aminoglycoside antibiotics and the correct drug dose was reached more quickly for oral anticoagulants. It significantly decreased thromboembolism (blood clotting) events for anticoagulants and tended to reduce unwanted effects for aminoglycoside antibiotics and anti-rejection drugs (although not an important difference). It tended to reduce the length of hospital stay compared with routine care with comparable or better cost-effectiveness. There was no evidence of effects on death or clinical side events for insulin (low blood sugar (hypoglycaemia)), anaesthetic agents, anti-rejection drugs (drugs taken to prevent rejection of a transplanted organ) and antidepressants. The quality of the studies was low so these results must be interpreted with caution.
We included five studies. These studies reported the effect of adding whole brain radiation to surgery or radiosurgery in terms of survival, brain disease progression, quality of life and treatment side effects. The sample size of these studies ranged from 19 to 359 patients. Adding whole brain radiotherapy to surgery or radiosurgery reduces brain metastases progression rates substantially but there was no clear evidence of an effect on survival and it is unclear whether it may cause side effects such as memory loss. We considered the evidence on survival, intracranial disease progression, neurocognitive function, quality of life and treatment side effects to be of low quality.
This systematic review identified four studies (108 participants) investigating immunosuppressive treatments for adults with biopsy-proven FSGS. Adult patients treated with cyclosporin A in combination with prednisone were more likely to achieve partial remission of nephrotic syndrome compared with prednisone alone, however this result is based on only one small study. No data was available on the progression to kidney failure or death.
This review found one small study, including 70 participants, which compared laser photocoagulation with no treatment for people with this disease. This study was inadequately reported and analysed, although it suggested a benefit with photocoagulation during the first two years of follow up. Another small study compared three laser wavelengths to achieve photocoagulation of the lesion, but actually had very little power to demonstrate a difference between them as only 27 participants were included. Therefore, despite its widespread use for many years, the amount of benefit achieved with photocoagulation and the possibility that it is maintained over the years remains unknown. Furthermore, these and other studies suggest that the enlargement of the laser scar could be a potentially vision-threatening long-term complication after two years, since it may cause the gradual occurrence of a blind spot in the centre of the visual field due to progressive atrophy of the retina.
In the current review, which looked for studies up to April 2015, we identified 13 studies involving 917 participants. Eleven studies evaluated topical treatments (medication applied to the skin), two trials studied an oral treatment, and two studies assessed a parenteral treatment (via injection or infusion). Seven studies used a control group that received no treatment or a placebo, whereas all others also or solely compared two active treatment groups. No study evaluated the effects of ice or the application of cold or hot bandages. Overall, topical treatments resulted in a higher and faster improvement of the clinical signs and symptoms compared to placebo or no intervention. Reporting on safety data was limited, with no available information on some treatments (notoginseny creams, parenteral low-molecular-weight heparin or defibrotide). Although some studies reported on harmful side effects with topical heparinoid creams, Essaven gel or phlebolan, the trials were too small in size to adequately measure any differences between treatments. Reported side effects of topical treatments consisted mainly of local allergic reactions. Only one study with 15 participants assessed anything other than localised control of the condition. That study reported on extension of the clot or symptomatic venous thromboembolism (when the blood clot breaks loose and travels in the blood stream), observing no cases when treated orally with non-steroidal anti-inflammatory drugs or with low-molecular-weight heparin. None of the studies reported on the development of suppurative or septic phlebitis (when pus is formed inside the vein or around the vein wall or both), catheter-related bloodstream infections or quality of life. Some of the included studies may have been biased due to design limitations, but we could not always assess this risk because the original researchers did not always provide enough information to judge. The overall quality of the evidence for each of the outcomes varied from low to moderate, mainly because the studies had design flaws or were very small. We could not analyse data on primary outcomes together because the trials examined different treatments, in different ways, looking at different outcomes. In short, the evidence about the treatment of acute infusion superficial thrombophlebitis is limited and of low quality, and we do not have enough information to recommend the use of any of the treatments studied.
Sixty-one trials were included which evaluated 58 induction phases (5111 patients randomised to placebo) and 12 maintenance phases (1579 patients randomised to placebo). The researchers found that placebo response and remission rates varied according to which class of drug was being tested with the highest placebo response rates observed for biological drugs (genetically engineered medications made from living organisms). The highest placebo remission rates were observed for trials evaluating aminosalicylates (a type of anti-inflammatory drug). The lowest placebo response and remission rates were in trials that assessed corticosteroids (drugs that suppress inflammation and immunity). The requirement of a minimum rectal bleeding score for study eligibility was associated with an increased placebo response rate compared to studies that did not use rectal bleeding for trial eligibility. The time point of primary outcome assessment was found to be significantly associated with placebo remission rates such that every one week increment in endpoint assessment was associated with an increase in the placebo remission rate. There were several trial design features that were associated with lower placebo response and remission rates. A key finding was that trials enrolling patients with more severe endoscopic disease (i.e. inflammation of the colon as confirmed by a colonoscopy) at trial entry were associated with lower placebo response and remission rates, which underpins the importance of objectively ensuring that patients enrolled into UC trials have sufficient disease severity. Disease duration of greater than five years prior to trial enrolment was associated with a significantly lower placebo response rate compared to disease duration of less than or equal to five years. The researchers also found that placebo rates have remained stable from 2008 to 2015. In conclusion, placebo response and remission rates vary according to endoscopic disease severity and rectal bleeding score at trial entry, drug class, disease duration, and the time point at which the primary outcome was measured. The overall findings will help researchers conducting trials to design their studies, determine the number of patients required for their planned trials and also provide useful information about trial design features which should be considered when planning new trials.
Twenty-nine eligible trials, involving 5247 participants, were identified. It confirms reports from individual trials that motor complications are reduced with dopamine agonists compared to levodopa, but also demonstrates that other important side-effects are increased and symptom control is poorer with agonists. Unfortunately, the balance of risks and benefits remains unclear highlighting the need for further studies assessing patient-rated overall quality of life and economic measures as their primary outcomes.
Only one randomised controlled study could be included in this review (including 154 preterm infants that needed breathing support). Indomethacin and surgery gave similar benefits. There were no differences in deaths during the hospital stay, chronic lung disease, necrotising enterocolitis, cerebral or other bleeding. Surgery was more effective in closing the PDA (three needed to treat for one to benefit) but it was associated with complications (pneumothorax and retinopathy of prematurity). The one study found was carried out over 30 years ago. Clinical practice has changed a great deal and surgical closure of a PDA is safer. Therefore, whether the results of the study are applicable today is debatable. Updates of this review in July 2007 and February 2012 did not identify any additional randomised controlled studies for inclusion, but three observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation: chronic lung disease, retinopathy of prematurity and neurosensory impairment.
This review found no clear overall benefit or harm from chest physiotherapy. Some individual chest physiotherapy techniques were more beneficial than others in resolving atelectasis and maintaining oxygenation. These results do not support one technique over another. Due to the limited number, poor quality and age of trials in this review, there is not enough evidence to determine whether or not chest physiotherapy is beneficial or harmful in the treatment of infants being ventilated in today's intensive care units. Further good quality trials are needed to address this issue.
Of the 91 included studies, 86 had information on small babies, of which 18 also looked at stillbirth; another five studies only looked at stillbirth. The most accurate test for detecting a small baby was ultrasound scan to estimate a baby’s weight. Of the substances measured in mother’s blood, human placental lactogen (hPL), a hormone produced by the placenta during pregnancy, was the most accurate. There was only one study which looked at both ultrasound scanning and measurement of a placental substance. Placental growth factor (PlGF) was the most accurate test of a placental substance to identify a baby that would be stillborn; there were no studies of ultrasound scanning to detect a baby that would be stillborn. Tests of placental substances were better at identifying a baby at risk of stillbirth than detecting a small baby. Many of the studies included in this review were carried out between 1974 and 2016. Studies of placental substances were mostly carried out before 1991 and after 2013; earlier studies may not reflect developments in test technology. More studies are needed to find out whether a combination of ultrasound scans and mother’s blood tests could improve identification of pregnancies which end in the birth of a small baby or in a stillborn baby. No studies were identified for this review that looked at the accuracy of ultrasound and blood tests used together.
Cochrane review authors evaluated randomised controlled trials (RCTs) that compared prolapse surgery with and without any perioperative (before, during, or after) interventions. The evidence is current to 30 November 2017. Reviewers included 15 trials that evaluated eight different interventions related to prolapse surgery. Although primary outcomes of the review were objective failure (recurrence of prolapse on examination) and awareness of prolapse, reviewers also measured adverse effects, focusing on intraoperative blood loss, intraoperative ureteral injury, postoperative urinary tract infection, and repeat surgery. Key results Reviewers found very little evidence on perioperative interventions in pelvic organ prolapse surgery. Few trials reported primary outcomes. A structured programme of pelvic floor muscle training before and after surgery did not consistently demonstrate any benefit for the intervention. With regard to other preoperative interventions, neither bowel preparation nor detailed preoperative mapping demonstrated significant benefit when compared to usual care. Intraoperative interventions such as injection of a vasoconstrictor agent, ureteral stent placement during uterosacral ligament suspension, or placement of a vaginal pack did not demonstrate benefit for reduced blood loss or rate of urinary tract infection or injury to the ureter. Vaginal packing postoperatively did not reduce the rate of haematoma (collection of blood) when compared to prolapse surgery without packing in a single trial. The rate of postoperative urinary tract infection was not reduced by use of a vaginal pack, prophylactic antibiotics, or vaginal dilators. Quality of the evidence The quality of the evidence ranged from very low to moderate. The main limitation was imprecision, associated with small sample sizes and low event rates.
We identified three trials that compared the efficacy of laparoscopic surgery and open surgery. These studies included 392 participants (195 in the laparoscopic group vs 197 in the open surgery group). The method used to allocate participants based on randomisation, that is, the choice of treatment that participants received, was determined by a method similar to coin tossing, so the two groups were as similar as possible. We found that laparoscopic surgical resection may lead to little or no difference in mean hospital stay when compared with open surgical resection. Operating time was longer in the laparoscopic group by an average of 49 minutes. No important differences were observed in terms of 30-day postoperative mortality, early overall morbidity, major and minor complications, surgical complications, postoperative times to liquid and solid diets, and reoperations due to anastomotic leak. To assess quality of life, researchers used different scales at different periods of time. Although one trial reported that patients who received laparoscopic surgery had better quality of life, the other two trials showed no benefit favouring either laparoscopic surgery or open surgery. The quality of the evidence varied from low to very low owing to risk of bias (i.e. conclusions may overestimate benefits or underestimate harms because of biased study design and conduct) and limitations in the patient population sample. Well-designed trials are necessary to obtain a more accurate estimate of the benefits and safety of laparoscopic surgery over open surgery.
The evidence is current to December 2016. We updated our search in November 2017, but these results have not yet been incorporated in the review. We included 15 completed randomized controlled trials involving 1822 participants. There are 8 ongoing studies and 12 waiting further assessment. None of the completed studies included infants or children. In four studies participants were undergoing abdominal or orthopaedic surgery, one study included participants undergoing a procedure to restore proper blood flow to the brain, and in the remaining 10 studies participants were undergoing large blood vessel or heart surgery with or without heart bypass. The studies all used cerebral NIRS in the operating room, with only two also using cerebral NIRS in the intensive care unit. The control groups were monitored using methods such as heart rate and mean arterial blood pressure, electroencephalogram, transcranial doppler, bispectral index, oxygen saturation in the jugular vein, evoked potentials or cerebral tissue oxygen partial pressure. Overall, the different studies varied in their approach to the review question. We did not pool (combine) the data for the outcome postoperative neurological injury because of variations between studies. One study with 126 participants having major abdominal surgery reported that 4/66 versus 0/56 participants experienced neurological injury with blinded and active monitoring, respectively. A second study with 195 participants undergoing coronary artery bypass surgery reported that 1/96 versus 4/94 participants suffered neurological injury in the blinded (masked) and active (with active treatments) monitoring groups, respectively. We are unsure whether active NIRS monitoring has an important effect on the risk of postoperative stroke and delirium because there was a low number of events and the result was not precise (2 studies, 240 participants; 1 study, 190 participants, respectively; low-quality evidence). Based on two studies with 126 participants, we found low-quality evidence that cerebral NIRS monitoring may reduce the number of participants with mild cognitive impairment at one week after surgery. Based on six studies with 962 participants, we found moderate-quality evidence that monitoring with cerebral NIRS probably leads to little or no decrease in the number of participants with a decline in cognitive function one week after surgery. We are uncertain whether active cerebral oxygenation monitoring has a crucial effect on intraoperative or postoperative deaths because there was a low number of events and the result was not precise (3 studies, 390 participants; low-quality evidence). We did not find any detrimental effects of the routine use of NIRS-based brain oxygenation monitoring. Overall, it is uncertain whether active NIRS monitoring has a crucial effect on postoperative stroke, delirium or death because of the imprecision of the results (low-quality evidence). Therefore, the effects of active cerebral NIRS monitoring on postoperative nervous system injury, delirium, decline in cognitive function and death are uncertain. For some outcomes, such as postoperative stroke or other neurological injury, the evidence was based on few studies with limited numbers of participants. Reporting of outcomes was often incomplete for all study participants, as was reporting of the study design, such as blinding. Some studies had potential conflicts of interest from industry sponsorship.
We identified 96 studies, up to December 2012, for inclusion in the review. These studies, involving 10,401 stroke survivors, investigated physical rehabilitation approaches aimed at promoting recovery of function or mobility in adult participants with a clinical diagnosis of stroke compared with no treatment, usual care or attention control or in comparisons of different physical rehabilitation approaches. The average number of participants in each study was 105: most studies (93%) included fewer than 200 participants, one study had more than 1000 participants, six had between 250 and 100 participants and 10 had 20 or fewer participants. Outcomes included measures of independence in activities of daily living (ADL), motor function (functional movement), balance, walking speed and length of stay. More than half of the studies (50/96) were carried out in China. These studies showed many differences in relation to the type of stroke and how severe it was, as well as differences in treatment, which varied according to both treatment type and duration. This review brings together evidence confirming that physical rehabilitation (often delivered by a physiotherapist, physical therapist or rehabilitation therapist) can improve function, balance and walking after stroke. It appears to be most beneficial when the therapist selects a mixture of different treatments for an individual patient from a wide range of available treatments. We were able to combine the results from 27 studies (3243 stroke survivors) that compared physical rehabilitation versus no treatment. Twenty-five of these 27 studies were carried out in China. Results showed that physical rehabilitation improves functional recovery, and that this improvement may last long-term. When we looked at studies that compared additional physical rehabilitation versus usual care or a control intervention, we found evidence to show that the additional physical treatment improved motor function (12 studies, 887 stroke survivors), standing balance (five studies, 246 stroke survivors) and walking speed (14 studies, 1126 stroke survivors). Very limited evidence suggests that, for comparisons of physical rehabilitation versus no treatment and versus usual care, treatment that appeared to be effective was given between 30 and 60 minutes per day, five to seven days per week, but further research is needed to confirm this. We also found evidence of greater benefit associated with a shorter time since stroke, but again further research is needed to confirm this. We found evidence showing that no one physical rehabilitation approach was more effective than any other approach. This finding means that physiotherapists should choose each individual patient's treatment according to the evidence available for that specific treatment, and should not limit their practice to a single 'named' approach. It was difficult for us to judge the quality of evidence because we found poor, incomplete or brief reporting of information. We determined that less than 50% of the studies were of good quality, and for most studies, the quality of the evidence was unclear from the information provided.
We identified three new relevant studies in this update. In total, this review now includes seven studies with 704 participants. Most of the participants (82%) were male; the average age across the studies was 29 years (range 12 to 90 years). All of the studies investigated just one comparison: immobilisation in external rotation (when the arm is orientated outwards with the forearm away from the chest) versus immobilisation in internal rotation (the usual sling position, where the arm rests against the chest) following closed reduction. Participants were followed over different lengths of time; the most common duration was two years or longer. We are uncertain whether immobilisation in external rotation makes a difference to the risk of re-dislocation at one-year or more follow-up compared with immobilisation in internal rotation. None of the four studies reporting on patient-reported outcome measures for shoulder instability at a minimum of one-year follow-up found evidence of any important difference between the two interventions. We are uncertain of the relative effects of the two methods of immobilisation on resumption of pre-injury activities or sports. One study found no evidence of a difference between interventions in the return to pre-injury activity of the affected arm. Two other studies found greater return to sports in the external rotation group in a small group of participants who had sustained their injury during sports activities. None of the trials reported on participant satisfaction or health-related quality of life. We are uncertain whether there is a difference between the two interventions in the number of participants experiencing instability, defined as either re-dislocation or subluxation (a partial dislocation). The reporting of adverse events (complications) was unsatisfactory. There were reports of nine cases of short-term shoulder stiffness in the external rotation group and two cases of under-arm rash in the internal fixation group. There were three more serious adverse events: abnormal sensitivity and hand pain; abnormal sensation such as tingling in the little finger and along to the elbow; and major movement restriction. It was unclear to what extent these three adverse events could be attributed to the treatment. We rated the certainty of the evidence as very low for all outcomes. This was mainly because there were not enough data and we were unsure how reliable the results were from the individual studies. Thus we are uncertain about the estimates of effect. Overall, the current evidence is insufficient to inform the choice of immobilisation in external versus internal rotation. There is no evidence to inform on any other conservative interventions following closed reduction of traumatic anterior dislocation of the shoulder.
This review looked at whether antibiotics are effective in preventing infection in women having a cesarean section. It also studied the effect of giving the antibiotics before or after the cord is clamped and different kinds of antibiotics. The review found 95 studies involving over 15,000 women. Routine use of antibiotics at cesarean section reduced the risk of wound and womb infections in mothers as well as the risk of serious complications of infections for the mothers by 60% to 70%. This was so whether the cesarean section was planned (elective) or not, and whether the antibiotics were given before or after clamping of the umbilical cord. The evidence to support antibiotic treatment was of moderate quality but often the way the study was done was not described well enough. None of the studies looked properly at possible adverse effects on the baby and so, although there are benefits for the mother, there is some uncertainty about whether there are any important effects on the baby.
The search, updated in May 2018, identified 14 studies that tested phonics training in 923 English-speaking poor readers. The studies took place in Australia, Canada, the UK, and the USA. Six of the 14 included studies were funded by government agencies and one was funded by a university grant. The rest were funded by charitable foundations or trusts. Each study compared phonics training alone, or with one other reading-related skill, to either no training (i.e. treatment as usual) or alterative training (e.g. maths). Participants were English-speaking children or adolescents, of low and middle socioeconomic status, whose reading was one year, one grade, or one standard deviation (distance from the average) below the level expected for their age or grade for no known reason. Phonics training varied between studies in frequency (up to four hours per week), duration (up to seven months), training group size (individual and small groups), and delivery (human and computer). We measured the effect of phonics training on poor readers' ability to read words and novel words (non-words) accurately and fluently, as well as their comprehension of text, and their knowledge of letter-sound rules (letter-sound knowledge) and speech sounds (phonological output). We found that phonics training in English-speaking poor readers probably improved irregular word reading accuracy, mixed/regular word reading fluency, and non-word reading fluency. It may also have improved mixed/regular word reading accuracy, non-word reading accuracy, reading comprehension, spelling, letter-sound knowledge, and phonological output. The overall quality of the evidence ranged from low to moderate. This was primarily due to large differences in the size of phonics-training effects between studies. More studies are needed to improve the precision of the outcomes. The evidence suggests that phonics training can improve literacy in English-speaking poor readers. The positive effects of phonics training on all reading-related outcomes suggests that phonics training is not harmful for poor readers.
We set out to review the effects of self-management education for cystic fibrosis on a range of health outcomes in individuals of all ages with cystic fibrosis and their caregivers. Our search for available evidence identified four trials, and all four compared a form of self-management education to standard treatment. The precise focus of self management differed between trials and included a training programme for managing cystic fibrosis, education on chest treatments, education on nutrition specific to cystic fibrosis, and education on general and disease-specific nutrition. Self-management education had no positive effects on lung function, weight, or intake of fatty food. There is some evidence to suggest that self-management education improves knowledge about cystic fibrosis and its management in patients with this condition and some self-management behaviours in patients and caregivers. However, due to the small number of trials in this review, and because of concerns about the quality of these trials, we are unable to reach any firm conclusions about the effects of self-management education for cystic fibrosis. We recommend that further trials are conducted to evaluate the effects of self-management education interventions.
This review identified 24 studies (4473 participants) comparing cranberry products with control or alternative treatments. There was a small trend towards fewer UTIs in people taking cranberry product compared to placebo or no treatment but this was not a significant finding. Many people in the studies stopped drinking the juice, suggesting it may not be an acceptable intervention. Cranberry juice does not appear to have a significant benefit in preventing UTIs and may be unacceptable to consume in the long term. Cranberry products (such as tablets or capsules) were also ineffective (although had the same effect as taking antibiotics), possibly due to lack of potency of the 'active ingredient'.
SPf66 has had 10 trials in Africa, Asia, and South America. Results were initially promising, but further trials showed only a small effect in some trials, and no effect in Africa. There is no evidence that SPf66 is effective enough to be introduced on a routine basis for prevention of malaria.
We searched our own specialised register of controlled trials. We also contacted Sanofi Aventis, the manufacturers of rimonabant, and researchers who presented early findings at conferences. We found two randomized controlled trials (RCTs) of rimonabant for smoking cessation, covering 1567 smokers, and one RCT of rimonabant for relapse prevention covering 1661 quitters. The available information shows that rimonabant at the 20 mg dose increased by 1½-fold the chances of not smoking at one year, compared with placebo. Rimonabant 5 mg did no better than placebo at any time point. In the relapse prevention trial, smokers who quit successfully with rimonabant 20 mg were 1½ times more likely to remain abstinent on active treatment (5 mg or 20 mg for 42 weeks) than on placebo. For those who quit successfully on 5 mg, neither active nor placebo treatment appeared to benefit them in avoiding relapse. This inconsistent picture makes it difficult to find a clear benefit for rimonabant in preventing relapse. One trial of taranabant (317 smokers) did not find a benefit for treatment over placebo, and the taranabant group suffered more side effects than the placebo group. Main side effects for rimonabant included nausea and upper respiratory tract infections, and serious harms were reported to be low. For taranabant, the main side effects included problems with digestive, nervous, psychiatric, skin and blood vessel organ systems. For both drugs, the number and severity of the side effects increased in those taking higher doses. Although the evidence on weight change is sparse in these trials, weight gain was reported to be significantly lower among the rimonabant 20 mg quitters than in the 5 mg or placebo quitters. During treatment, overweight or obese smokers tended to lose weight on 20 mg, while normal weight smokers did not. Taranabant also limited weight gain during cessation attempts. In 2008 both rimonabant and taranabant were withdrawn by the manufacturers, because of links to mental disorders and unacceptable side effects.
We searched for evidence in April 2016 and identified one randomised controlled trial including 40 babies. Investigators reported a small decrease in the concentration of alkaline phosphatase (an enzyme involved in bone growth) among infants who had received calcium/phosphorus supplementation. We found no difference in growth between infants who had been given human milk supplemented with extra calcium and phosphorus and infants who had received no supplementation. One small trial provided the evidence, and we judged the evidence to be of low quality. Researchers reported no follow-up of these babies into childhood. Evidence is insufficient to allow a judgement as to whether extra calcium and/or phosphorus provided to preterm babies confers benefit for their bones and growth. It is no longer very common to give calcium and phosphorus supplements alone, as human milk fortifiers now available include many other components as well as minerals to support the growth and development of preterm babies. We therefore suggest that future trials conducted to examine effects of mineral supplements in preterm babies include them in multi-component human milk fortifiers and assess clinically important outcomes into childhood.
The statistical evidence for efficacy in 'possible or probable Alzheimer's disease' patients was so modest however that one additional statistically non-significant trial would have reduced the results to non significance; evidence for efficacy in vascular dementia rested on relatively stronger effects for hydergine on clinical ratings; and effective doses may be higher than 3 mg/d (i.e., than that currently approved in the USA). Despite its availability for 40 years, the circumstances of hydergine's efficacy in dementia syndromes have not been adequately researched, and have yet to be precisely defined.
We included three randomised controlled trials in which women were allocated at random to receive one of several interventions (treatments) and which involved 161 obese participants. The trials were conducted in the USA and the UK. All compared lifestyle advice (diet and exercise) plus self-help techniques (to encourage adherence to the advice) with usual care. The evidence is current to January 2018. We found no benefit for endometrial cancer survivors from receiving lifestyle advice in terms of survival, cardiovascular events or quality of life, though such interventions were not associated with significant or serious harms to participants. They did, however, report higher rates of musculoskeletal symptoms, presumably due to increases in physical activity. Whilst some women lost weight with these interventions, others did not, meaning that overall there was little or no benefit. The quality of included studies was, however, low or very low and all were small in terms of the number of participants and not designed to specifically look at the effect of their intervention on survival. Additional high-quality studies are required in this field and currently there are five ongoing trials.
Sepsis is the inflammatory response of the body to severe infection, which can be caused by a variety of micro-organisms including bacteria, viruses and fungi. Signs of sepsis include fever, hypothermia, rapid heart rate and respiration; and a laboratory finding of increased or decreased white blood cell count. Deaths as a result of sepsis and septic shock remain high despite giving antibiotics, especially if the functions of a persons's vital organs such as the lungs, heart and kidneys are affected. Several studies have looked into other agents than antibiotics to help the body fight the effects of sepsis. Intravenous immunoglobulin preparations contain antibodies that help the body to neutralize bacterial toxins. There are two types of preparations. These are polyclonal immunoglobulins that contain several antibodies directed at endotoxin and inflammatory mediators, and monoclonal immunoglobulins which target a specific inflammatory mediator or antigen. Intravenous immunoglobulins are blood products, specifically pooled sera derived from human donor blood. For this updated Cochrane review, we searched the medical literature databases to January 2012. We included 43 randomized controlled trials (RCTs); 25 were RCTs of polyclonal intravenous immunoglobulins (IVIGs) with 17 in adults (1958 participants) and eight in newborn infants (3831 participants) including a large polyclonal IVIG trial on infants with sepsis that was published in 2011. The remaining 18 trials (a total of 13,413 participants) were of monoclonal antibodies. Both standard and immunoglobulin M (IgM)-enriched polyclonal immunoglobulins decreased the number of deaths in adults but not in infants. However, no reductions in adult deaths were seen with polyclonal IVIG using high quality trials only. Among newborn infants with sepsis, there is definitive evidence that standard polyclonal IVIG does not reduce the number of deaths. In the monoclonal immunoglobulin trials, anti-endotoxin antibodies showed no benefit while the anti-cytokines showed a very small reduction in deaths among adults with sepsis. The polyclonal immunoglobulin trials in adults were small compared to the trials of monoclonal agents. The reduction in deaths observed with polyclonal IgM-enriched preparations as add-on therapy for sepsis needs to be confirmed in large studies that use high quality methods.
The evidence is current to March 2016. We did not find any trials in adult populations and included three trials involving 420 children. All trials were set in countries where death rates for meningitis are high. In one study no funding source was mentioned. The remaining two studies were funded jointly by pharmaceutical concerns with government agencies and a charitable agency. No studies reported important healthcare outcomes such as duration of hospital stay, raised intracranial pressure, or status epilepticus. An adverse effect in children with restricted fluid intake was that they were less likely to have low levels of sodium in their blood and therefore they would experience greater reductions in body fluids. An adverse effect of unrestricted fluid administration was reported in one study as short-term swelling of the face and low blood sodium levels one to two days after fluids were started, although the largest study found no difference in blood sodium levels. Quality of the evidenceAnalysis of available trials found low quality evidence that there is no significant difference between maintenance versus restrictive fluid regimens for the outcome of death and acute severe neurological complications. There was also some evidence favouring maintenance fluid therapy over restricted fluids for chronic severe neurological events at three months follow-up, but the quality was very low.
In this review, the authors looked for studies (randomised controlled trials (RCTs)) from around the world to find out how women with ovarian cancer were assessed to see if they were eating and drinking well and what help they may be given with nutrition before or after surgery. A lack of information was found on this topic. One RCT was found where a small group of women (40 including 35 with ovarian cancer) requiring extensive elective surgery for gynaecological cancer including surgery to the gut, were able to restart eating normal foods on the day after surgery. They were able to leave hospital earlier and did not have more complications in the month after surgery than women who were not allowed to resume eating normal foods until at least three days after the operation. More studies are needed to confirm whether restarting normal eating one day after surgery can be recommended for women having surgery for ovarian cancer. More research is needed to provide information about how to identify and treat problems of malnutrition in women with ovarian cancer.
We included a single study with 11 reports that focused on results for different outcomes. The participants of the included study were 46 children aged 8 to 18 years recruited from the clinic of a tertiary hospital in Melbourne, Australia who were diagnosed with long-term constipation either based on their symptoms and/or X-ray studies. The studies divided the patients into two groups, one receiving the actual TES , with electrodes placed on their belly and electrical current running, and the other receiving sham stimulation, with identical device administered but without the electrical current. The participants were followed-up for up to four years, although only outcome information up until the follow-up period of two months were available in this review. The study was funded by the Australian National Health and Medical Research Council and Murdoch Children's Research Institute Theme Investment Grants. There was not enough information on certain aspects of the trial methodologies from the reports gathered, although it was clear that the physiotherapists who administered the TES treatment or sham treatment were aware of which group the patients were allocated to. The knowledge of the participants' allocated group might have influenced the way the actual and sham therapies were administered, as well as the way some of the outcome data, such as symptoms of constipation and soiling and quality of life, might have been reported by the therapist as well as the patients and their carers. This raised concerns regarding the overall methodological quality of the study. The very low quality evidence for all of the results means that we are uncertain about the effects of TES when compared with sham stimulation. Overall, there were no differences between children who received TES and sham stimulation in the number of children with improved complete spontaneous bowel movements, improved bowel movements (as assessed by X-Ray with special contrast), improved symptoms related to soiling and quality of life. There were also no differences between the two groups in the average change in the quality of life scores after the therapy, as assessed by the children themselves as well as their parents. The only difference noted was in mean bowel transit rate, namely, distance travelled by the radioactive substance along the bowel, in which children who received TES had their radioactive substance slightly further down their bowel compared to children who received a sham stimulation. However, it was unclear whether such a difference in distance travelled in the bowel translated to any meaningful differences in defaecation and constipation-related symptoms. No side effects were reported in the study. Overall, this study included a small number of patients and we had concerns regarding the methods resulting in very low quality evidence for all the outcomes assessed. The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the effectiveness and side effects of TES in children with chronic constipation can be drawn. Further studies assessing TES for the management of constipation are needed. We suggest that future research should provide clear documentation on specific methods in the conduct of the trials, and include outcomes that are important for patients, such as spontaneous or complete bowel movements or improvement in constipation-related symptoms along with assessments of quality of life.
In this review we were interested in whether giving babies sugar-based solutions to taste when the needle breaks the skin will help reduce their pain. We found 14 separate studies that had asked this question. However, the differences between the studies were often too great to let us combine their findings. Overall, the studies show that different types of sugar-based solutions were effective but we were not able to confidently assert that there is strong evidence for this treatment in reducing pain. We did find some evidence that babies may not cry for as long if given sugar-based solutions. This review is broadly in agreement with two other reviews, one asking this question in younger children, and one in older children. There is a need for better studies in this field.
The aim of this review is to compare the efficacy of the various forms of drug treatment that have been used to treat psychotic depression. We did this by analysing all randomised controlled trials (RCTs) that investigated drug treatments for psychotic depression. We searched for these trials in a wide-ranging way. The search identified 3659 studies, but in the end, we found only 12 RCTs that met our inclusion criteria. These trials involved a total of 929 people. From these trials, we found evidence that the combination of an antidepressant plus an antipsychotic provides more effective treatment for psychotic depression than either treatment alone. However, our confidence in this conclusion is limited because the information came from only a small number of RCTs, which included small numbers of people. In addition, the types of people involved varied between RCTs, and the RCTs differed in design, which means that we cannot confidently generalise their findings.
We wanted to know which of these two methods is more likely to detect poor growth. Ultrasound assessment can also be used to detect growth restriction but this is costly and not always available, and there are concerns about its unnecessary use. We found only one randomised trial (involving 1639 women at 20 weeks’ gestation and above) comparing repeated measures of SFH with abdominal palpation. The trial found no difference between the two approaches in detecting poor growth. With such limited evidence, it is still not known whether one method is more effective than the other, and how these methods compare with ultrasound measurement. The main findings from this review were assessed for quality using software called GRADEpro. The overall evidence was of low/very low quality.
We searched the medical literature until 30 April 2013 for studies comparing different methods of treating fingertip entrapment injuries. Our review includes evidence from two studies where participants were randomly allocated to one of two conditions. The studies included 191 children with results available for a total of 180 children. Both the studies had weaknesses that could undermine the reliability of the results. Since the studies compared different methods, we could not combine their results. One study looked at the routine use of antibiotics in children with a surgically repaired fingertip injury to prevent infection. Due to the small number of children experiencing infection this study does not provide conclusive evidence of the effect of giving or withholding antibiotics. Only one child in each group had an infection after a week. Both children had had more severe injuries. The other study compared two different dressing types for use in fingertip entrapment injuries. The low number of complications was comparable in the two treatment groups. Due to the low number of participants in the study we could not be certain that length of time the injuries took to heal and the number of dressing changes were the same in the treatment groups. However, it also found that the dressing made of silicone caused less distress for the child when being changed after the first week, probably because it stuck less to the wound than the paraffin dressing. Overall, there is not enough evidence about how to best treat fingertip entrapment injuries in children. We recommend that further research is carried out, especially to see if surgery leads to better outcomes than simple wound cleaning and dressing. These studies should evaluate the effect of the treatment on fingertip function, nail growth and nail deformity for a minimum of three months after treatment.
This review asked the question whether there are any benefits or dangers of using this type of care. We found only data of limited quality and or applicability, so no clear answers are possible. The seven studies we looked at suggested that home management of children newly diagnosed with type 1 diabetes does not lead to any disadvantages in terms of blood glucose, acute diabetic complications and hospitalisations, psychological variables and behaviour, or total costs. This would be particularly relevant for children not acutely ill, but also for children who require a short period of initial treatment in the hospital.
This review looked for randomized trials comparing Huperzine A with control in patients with AD. Six trials were identified but most trials were of low methodological quality. Although Huperzine A seemed to have some beneficial effects on improvement of general cognitive function, global clinical status, behavioral disturbance and functional performance for patients with AD, the small trials with limited numbers of patients and the low methodological quality resulted in cautious assessment of the results. More large, high-quality randomized trials are needed.
We searched various databases until 23 May 2018. Only one study, which was conducted in Iran, is included in our review. The study ran for two years and involved 20 people with OAC aged between 25 and 56 years. Participants were divided into two groups and two surgical treatments were compared for treating oro-antral communications; one group was treated with pedicled buccal fat pad flap (PBFPF) and the other with buccal flap (BF). The study did not find evidence of a difference between PBFPF and BF in terms of successful (complete) closure of OAC. Both interventions resulted in successful closure by one month after surgery. The study did not therefore report any adverse effects of treatment failure. It may not be possible to generalise these findings because the quality of the evidence was very low, due to unclear risk of bias and the small numbers studied in the single included trial. The evidence currently available is insufficient to draw reliable conclusions regarding the effects of interventions used to treat OAC or fistulae due to dental procedures. More well-designed and well-reported trials evaluating different interventions are needed to provide reliable evidence to inform clinical decisions.
We included 15 trials with 3129 ICU surgical or medical participants from academic hospitals. Four studies used parenteral nutrition and nine studies used only enteral nutrition. The route was unclear in the remaining two studies. While the studies planned to give different amounts of calories in the experimental and control groups, the actual difference in calories was small. Most studies were funded by the US government or non-governmental associations, but three studies received funding from the industry. Five studies did not state how they were funded. The differences in the type of nutrition and type of participants across studies did not allow us to combine study results, so we describe the range of results across the individual studies. The number of deaths at the hospital, in the ICU and at 30 days in those who received low-calorie nutrition was similar to those in the control group. The length of hospital and ICU stay and the length of mechanical ventilation varied across studies, sometimes shorter and sometimes longer when compared to the control group. The number of infections also varied across studies. We tried to analyse subgroups of participants in order to clarify this variation, but the results were not consistent. The overall quality of evidence for each outcome according to GRADE classification varied from very low to low. This was due to problems in the design and conduct of the studies, the variation in the study results (inconsistency between studies) and the wide range of possible results (imprecision).
The review of 121 trials found that larger doses of misoprostol are more effective than prostaglandin and that oxytocin is used in addition less often. However, misoprostol also increases hyperstimulation of the uterus. With smaller doses, the results are similar to other methods. The trials reviewed are too small to determine whether the risk of rupture of the uterus is increased. More research is needed into the safety and best dosages of misoprostol. Another Cochrane review has shown that the oral route of administration is preferable to the vaginal route.
We found seven randomised controlled trials, which included 324 adults and children with eczema. We conducted the search up to 14 August 2014. Two of the seven trials included only children; four included children and adults; and one only included adults. Four of the seven trials compared treatments made up of multiple different house dust mite reduction and avoidance measures, and three trials tested a single treatment. The treatments were compared against other house dust mite reduction or avoidance treatments, no treatment, a placebo intervention (e.g., cotton bed covers), or standard care only. We did not find any evidence to inform clinical practice. Some small treatment responses reported were in people with atopic eczema who were sensitive to one or more airborne allergens. We found no evidence of benefit in the other six included studies. Therefore, their use in the eczema population as a whole is unknown. High-quality longer trials of single, easy-to-use house dust mite reduction or avoidance measures should be performed. These seven very low-quality (Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach) small trials do not provide enough evidence to recommend any of the house dust mite reduction and avoidance measures tested.
We included 19 studies that recruited 1099 adults in total (studies ranged in size from 8 to 209 participants, but most (12 out of 19) had fewer than 25 participants per treatment group). The studies focused on people who were given immunonutrition or a standard feed before and after or only after their surgery. The studies varied in the length of time over which people were given the feeds, but this was usually at least five days. The evidence is current to February 2018. We did not find evidence of a difference in the length of hospital stay but there was wide variation between the individual studies in what they showed. We found some evidence that people who had immunonutrition may be about half as likely to have breakdown of their surgical wound called a fistula (a channel between the inside of the throat and the surface skin). We found no evidence that immunonutrition had any effect on wound infection (but not all studies were clear in how they measured this) or death. Study feeds were generally well tolerated and there was no evidence of a difference in adverse events such as diarrhoea between treatment groups. Other clinical complications such as pneumonia and urinary tract infections were not commonly reported, but there was little evidence of a reduction with immunonutrition. Most studies included in this review were small and poorly reported, which means that their results may be less reliable. More studies are needed that are larger, of better quality and conducted within current healthcare systems.
This review aimed to find out how effective ergonomic treatments were in treating CTS. Only two studies were found (involving 105 participants). Both were designed to minimise research biases, but neither was of high quality. Neither study assessed short-term overall improvement, adverse effects or need for surgery as outcomes. One small study (25 participants) found an ergonomic keyboard reduced pain after 12 weeks but the second study reported no difference in pain severity between the keyboard groups at six months. Neither study found improvements in hand function or signs of CTS by people using ergonomic computer keyboards more than those experienced by people using standard keyboards. Based on the two studies in this review, which represent all the available evidence of sufficient quality for inclusion, there is no strong evidence for or against the use of ergonomic keyboards for the treatment of CTS.
Authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 17 June 2015. It includes 14 studies published from 1991 to 2015 in which 1316 participants were randomised (1280 of whom were included in the analyses) to receive oral cryotherapy versus standard care (usually saline mouthrinses) or no treatment or a different treatment or a different method of oral cryotherapy, and the number of people developing oral mucositis of different severities was compared. Nearly all the evidence was on adults receiving oral cryotherapy versus standard care or no treatment. This evidence fell into two main groups: 1) adults receiving fluorouracil-based (5FU) treatment for solid cancers; or 2) adults receiving high-dose melphalan-based cancer treatment before haematopoietic stem cell transplantation (HSCT). HSCT is given to help the body to produce all types of blood cells, which are destroyed during cancer treatment. There is evidence showing that oral cryotherapy can lead to large reductions in the numbers of adults who get oral mucositis of all severities after receiving 5FU-based treatment for solid cancers. There is less certain evidence to suggest that oral cryotherapy may reduce the numbers of adults who get oral mucositis after receiving high-dose melphalan-based cancer treatment prior to HSCT. The evidence suggests that it does reduce oral mucositis in these adults, but the size of the reduction is much less certain. However, there is more certain evidence that there is a large reduction in severe oral mucositis in these adults. Oral cryotherapy did not cause any serious side effects in any of the participants of these studies, and most people seemed able to carry it out properly and complete it. The evidence presented, on the main outcome of whether or not people developed oral mucositis of all severities, is of moderate (because the nature of the oral cryotherapy treatment meant that the studies could not be 'blinded' which is a desirable characteristic of these studies) to low quality (because in addition to the above problem, the results of the individual studies were too different to give a precise result when they were combined).
The evidence is current to January 2019. We included nine studies (randomised controlled trials, that is studies in which participants are assigned to one of two or more treatment groups using a random method) of 2955 infertile couples undergoing IVF or ICSI. There were three different study designs: (1) TLS with conventional assessment of still TLS images versus conventional incubation and assessment; (2) TLS utilising embryo selection software versus TLS with conventional assessment of still TLS images; and (3) TLS utilising embryo selection software versus conventional incubation and assessment. TLS with conventional assessment of still TLS images versus conventional incubation and assessment All the evidence for this comparison was low-quality. It is unclear whether there is any difference between the interventions in rates of livebirth or ongoing pregnancy or miscarriage. The evidence suggests that if the rate of livebirth or ongoing pregnancy associated with conventional incubation and assessment is 35%, the rate with use of TLS with conventional morphological assessment of still TLS images would be between 27% and 40%, and if the miscarriage rate with conventional incubation is 4%, the rate associated with conventional morphological assessment of still TLS images would be between 4% and 14%. It is unclear whether there is a difference between interventions in rates of stillbirth or clinical pregnancy. TLS utilising embryo selection software versus TLS with conventional assessment of still TLS images All findings for this comparison were very uncertain due to very low-quality evidence. No data were available on livebirth, but one study reported ongoing pregnancy. It is unclear whether there is any difference between interventions in rates of ongoing pregnancy, miscarriage, or clinical pregnancy. The evidence suggests that if the rate of ongoing pregnancy associated with TLS with conventional morphological assessment of still TLS images is 47%, the rate associated with TLS utilising embryo selection software would be between 22% and 52%, and if the miscarriage rate associated with conventional morphological assessment of still TLS images is 5%, the rate associated with TLS utilising embryo selection software would be between 4% and 15%. No studies reported stillbirth. TLS utilising embryo selection software versus conventional incubation and assessment All findings for this comparison were very uncertain due to the very low-quality of the evidence. It is unclear whether there is any difference between interventions with respect to rates of livebirth or clinical pregnancy. The evidence suggests lower rates of miscarriage in the TLS group for the outcome of miscarriage. The evidence suggests that if the livebirth rate associated with conventional incubation is 48%, the rate with the use of TLS would be between 46% and 55%, and if the miscarriage rate with conventional incubation is 11%, the rate associated with TLS would be between 5% and 10%. There is no good evidence showing that TLS is more or less effective than conventional methods of embryo incubation. Patients may wish to take part in randomised controlled trials on TLS in order to add to the existing evidence base and to help guide assisted reproductive technology patients in the future. The quality of the evidence ranged from very low to low. The main limitations were high risk of bias in the included studies, imprecision, indirectness, and inconsistency.
This review included 23 trials, involving a total of 8447 participants. The review found that antibiotics are effective in reducing the incidence of infection, both at the surgical-wound site and in the chest and urinary tract. The effect of a single dose of antibiotic is similar to that from multiple doses if the antibiotic chosen is active through the period from the beginning of surgery until the wound is sealed. There were too few data available to confirm the expected tendency for increased adverse drug-related events such as gut problems and skin reactions.
We identified four studies. One randomised study (clinical trials where people are randomly allocated to one of two or more treatment groups) compared sublingual glucose administration, in the form of table sugar, with an oral administration in 42 hypoglycaemic children between one and 15 years old. Two non-randomised studies compared buccal glucose administration with oral administration in 23 adult healthy fasting volunteers. One randomised study compared a dextrose gel with oral administration of glucose in 18 people with type 1 diabetes and hypoglycaemia. Providing sugar under the tongue (sublingual) resulted in a greater rise in blood glucose after 20 minutes than giving the sugar orally, but this was in a specific setting including children with hypoglycaemia and symptoms of concomitant malaria or respiratory tract infection. On the other hand, giving glucose by the buccal mucosa route resulted in a lower plasma glucose concentration than with the oral route. For dextrose gel (where uptake of the glucose occurs through a combination of oral swallowing and via the buccal mucosa), no clear benefit was shown compared to oral glucose administration (glucose tablets or glucose solutions). Most studies did not report on time to resolution of symptoms, resolution of hypoglycaemia as defined by blood glucose levels above a certain threshold, time to resolution of hypoglycaemia, adverse events, and treatment delay. The evidence is of very low certainty due to limitations in study design, few studies and small number of participants in the studies, and because half of the studies were performed with healthy volunteers rather than in people with characteristic hypoglycaemia.
We included three studies in our systematic review. Altogether the studies evaluated 2971 participants, with 1467 participants allocated to the intervention groups and 1504 to the control groups. The studies had a length of intervention of 9, 12 and 24 months. This plain language summary was current as of December 2013. The use of the TTM SOC in combination with diet or physical activity, or both, and other interventions in the included studies provided inconclusive evidence about the impact of such interventions on sustainable weight loss (mean difference in favour of the TTM SOC was between 2.1 kg and 0.2 kg at 24 months). However, other positive effects were noted, such as changes in physical activity and dietary habits that included increased exercise duration and frequency, reduced fat intake and increased fruit and vegetable consumption. The studies did not report other important outcomes such as health-related quality of life, illness (morbidity) and economic costs. Overall, the quality of the evidence was low or very low. The main limitations included incomplete reporting of outcomes, methodological shortcomings, extensive use of self-reported measures and insufficient assessment of sustainability due to the lack of long-term assessments.
This review found no studies that compared the benefits and costs of early screening versus not screening for hip problems. Studies that compared the addition of ultrasound to clinical examination reported that when ultrasound was performed on all infants, the rate of treatment increased with no significant difference in rate of late detected dysplasia or surgery. Targeted ultrasound to infants at high risk of hip dysplasia did not significantly increase the rate of treatment but also did not significantly reduce the rate of late detected dysplasia or surgery. It is not possible to give clear recommendations for hip screening of newborn infants from the available evidence. Where infants are clinically detected as having unstable but not dislocated hips, or are detected on ultrasound to have mild hip dysplasia, there is evidence that delaying treatment by two to eight weeks reduces the need for treatment without a significant increase in late diagnosed dysplasia or surgery.
In this review we found seven studies that were eligible for inclusion, of which four studies compared the efficacy of oxcarbazepine to placebo or to other medications used in treating mania. While there was no evidence that oxcarbazepine worked better compared to a placebo, it did have similar efficacy to more accepted medications for the treatment of the illness. Two studies examined its acceptability to participants. Oxcarbazepine may cause more side effects than placebo. No differences in side effects were found between oxcarbazepine and other active medications. All the studies examined mania, hypomania, mixed episodes or rapid-cycling disorder. More studies of better methodological quality are needed if we are to be certain whether oxcarbazepine works or not when treating mania, mixed episodes, depression and rapid-cycling in bipolar disorder.
We searched clinical trial databases to look for any evidence of effectiveness and safety of HRT use in women who had had endometrial cancer up to May 2017. We only found one study that randomly allocated women to receive either HRT or a placebo (pretend treatment). This found no difference in the likelihood of the cancer regrowth between the two groups. They showed that HRT may or may not increase the risk of recurrence of developing a new cancer. They did not provide any information on survival or symptom relief. However, the study was not completed due to poor recruitment into the clinical trial, so was not large enough to definitively say whether the use of HRT could be recommended after treatment for early endometrial cancer. We are uncertain whether HRT increases the risk of recurrence after a diagnosis of endometrial cancer, as the certainty of the current evidence was very low. We identified only one randomised trial and this trial did not include enough women to definitely answer the question. This trial also had areas of potential bias that reduced our certainty in the results. Limited, very-low certainty, evidence suggests that HRT may have little or no effect on the risk of endometrial cancer returning for women who have been treated surgically for an early-stage endometrial cancer. There were no data to say whether HRT had an effect on overall survival after hysterectomy for endometrial cancer.
For this updated review, we identified five new studies (606 participants), bringing the total number of studies to 12, involving 2171 participants with COPD. The average age of participants was 66 years, 67% were male and participants had received a diagnosis of moderate to severe COPD. Eleven studies compared an injectable vaccine versus a control, and one study compared two different types of injectable vaccine. Key results People who were vaccinated were less likely to experience an episode of community-acquired pneumonia; 19 people with COPD (95% confidence interval (CI) 13 to 52) would have to be vaccinated to prevent one episode of pneumonia. Vaccination made no difference in the risk of pneumococcal pneumonia due to S pneumoniae or in the chance of dying or of being admitted to hospital. People who were vaccinated were less likely to experience a COPD exacerbation; eight people with COPD (95% CI 5 to 58) would have to be vaccinated to prevent one person from having an acute exacerbation. We found no difference in effectiveness between the two types of injectable vaccine. Quality of the evidence Evidence in this review is generally independent and reliable, and we are moderately certain about the results. Conclusions In line with current guidance, this review suggests that all people with COPD should be given pneumococcal vaccination to provide some protection against community-acquired pneumonia, and to reduce the chance of an acute exacerbation.
In the epsilon aminocaproic acid trial, the trial physicians assigned each person to receive a placebo or the active treatment based on a pair-matching technique for age, factor-assay and the number of extractions. The fact that the trial physicians made this decision may have introduced a selection bias. However, we do not think that this had a major impact on the trial's conclusions. Overall, the two trials were small and differed from each other in terms of how many of the people taking part had severe haemophilia, the simultaneous use of clotting factor concentrates and the different antifibrinolytic treatment schedules. We rated the overall quality of the evidence as low for using antifibrinolytic medicine to prevent bleeding in people with haemophilia after minor oral surgery or dental extractions. No evidence was found for people with Von Willebrand disease. It could however be argued that, if antifibrinolytic medicine works for people with haemophilia, it is likely that the medicine will also work for people with other bleeding disorders undergoing dental extractions or minor oral surgery.
Five randomised trials involving 153 women (154 pregnancies) were included. These trials did not report many of the outcomes we had hoped to look at. The evidence was judged to be very low quality for important outcomes (caesarean section, large-for-gestational age, perinatal mortality, and neonatal hypoglycaemia). This was because the trials were small, may not have been fair tests, and did not show a clear difference between MDI and CSII. There were no clear differences in any of the reported outcomes between women who had insulin via a pump rather than as multiple injections. For mothers, this included caesarean section, weight gain during pregnancy, and blood sugar levels. For babies, this included the baby's weight, if they were born premature, and problems such as difficulty breathing, a low Apgar score at birth, low blood sugar, jaundice, or physical abnormalities. In one small trial, there was no difference in the number of days mothers spent in hospital. This was the only measure of cost or use of health service resources reported. The trials did not provide enough information to know whether an insulin pump or multiple injections are better for a pregnant woman with diabetes or her baby. More research is needed, with bigger groups of women, good reporting of how the trials were undertaken, more outcomes assessed and reported, and using the latest pump technology and insulins.
We found evidence from one small trial to suggest that parenteral nutrition may result in an increase in weight, serum albumin levels and calorie and protein intake when compared to enteral nutrition (usual food intake). However, the effect of other methods of delivery of nutritional support remains unclear. Results from another small study suggested that the use of energy dense enteral feeds resulted in greater average daily energy intake and subsequently improved weight gain. Three studies looked at glutamine supplementation and did not show a benefit from its use. One study looked at the effect of using olive oil based parenteral feeds rather than those containing standard fats and found that it lead to less weight gain. One study considered the effect of adding fructooligosaccharide to enteral feeds and found that it did not effect the amount of weight gained or how often participants felt nauseated. No studies were identified that compared the nutritional content in either the PN or EN groups of studies. The trials were all of low quality and very different in terms of outcome measures used. In the future, much larger, rigorously conducted trials are needed in order to address this important question.
The evidence is current to August 2017. We included 106 studies with a total of 15,027 critically ill participants of any age and any gender. Relevant effects were found for the following drugs: H2 receptor antagonists, antacids, sucralfate, and proton pump inhibitors. H2 receptor antagonists inhibit gastric acid secretion by blocking histamine receptors but can cause a small number of blood platelets (thrombocytopaenia), inflammation of the kidney (interstitial nephritis), and confusion. Antacids neutralise stomach acid but may cause diarrhoea or constipation. Proton pump inhibitors inhibit the final stage of gastric acid production, and it has been found that they may be associated with increased risk of Clostridium difficile diarrhoea. Ulcer protective agents, such as sucralfate, create a barrier between the gastric acid and the gastric mucosa by coating it. They may, however, cause constipation and interfere with the absorption of certain antibacterial agents. In comparison with placebo or no preventive treatment, H2 receptor antagonists, antacids, and sucralfate might be effective in preventing clinically important upper GI bleeding in ICU patients. Hospital-acquired pneumonia was most likely to occur in ICU patients taking either H2 receptor antagonists or sucralfate when compared with patients given placebo or no preventive treatment. Evidence of low certainty suggests that proton pump inhibitors were more effective than H2 receptor antagonists in preventing upper GI bleeding in ICU patients. With proton pump inhibitors, 25 of 1000 people were likely to develop upper GI bleeding, and with H2 receptor antagonists, 73 of 1000 people (95% confidence interval 46 to 115 people) were likely to develop upper GI bleeding. The effect of H2 receptor antagonists versus proton pump inhibitors with respect to the risk for developing hospital-acquired pneumonia was consistent with benefits and harms. Our certainty in the evidence ranged from low to moderate. For effects of different interventions compared with placebo or no prophylaxis, the certainty of evidence was moderate (H2 receptor antagonists) or low (antacids and sucralfate). For effects of H2 receptor antagonists compared with placebo or no preventive treatment on risk of hospital-acquired pneumonia, the certainty of evidence was low. For effects of H2 receptor antagonists compared with proton pump inhibitors on hospital-acquired pneumonia, the certainty of evidence was also low.
We found eleven studies with 172 participants to include in the review. All studies compared low-flow oxygen to room air. Ten of the studies were short-term. Four of the studies looked at giving additional oxygen at night. At night, oxygen levels rose during both rapid eye movement (REM) sleep and non-REM sleep in those people breathing low-flow oxygen. Participants breathing oxygen at night also spent less time in REM sleep and took less time to fall asleep. Six of the studies looked at the effect of extra oxygen on exercise. The levels of oxygen and carbon dioxide in the blood of participants increased during or after exercise when they breathed in low-flow oxygen. People were able to exercise for longer if they breathed in low-flow oxygen. There was more regular attendance at school or work in those receiving long-term oxygen. There is little evidence to support or oppose the long-term use of oxygen therapy in people with advanced CF lung disease. In the short term, treatment has shown some improvement in blood oxygen levels in people with CF during sleep and exercise. This increase in oxygen also came with an increase in carbon dioxide levels, which is probably not clinically important. However, caution needs to be exercised in those with advanced lung disease where this may require further monitoring. There should be research into the effects of long-term oxygen treatment on sleep quality and exercise in people with CF. Unfortunately, we do not expect that any such research will be undertaken any time soon, so we do not plan to update this review again until we find any new trials.
We found 10 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) comparing the short-acting insulin analogues insulin lispro, insulin aspart, or insulin glulisine to regular human insulin in 2751 participants. The people in the included trials were monitored (followed) for 24 to 104 weeks. This evidence is up to date as of 31 October 2018. We are uncertain whether short-acting insulin analogues are better than regular human insulin for long-term blood glucose control or for reducing the number of times blood sugar levels drop below normal (hypoglycaemic episodes). The studies were too short to reliably investigate death from any cause. We found no clear effect of insulin analogues on health-related quality of life. We found no information on late diabetes complications, such as problems with the eyes, kidneys, or feet. No study reported on socioeconomic effects, such as costs of the intervention and absence from work. The overall certainty of the included studies was low or very low for most outcomes, mainly because all studies were carried out in an open-labelled fashion (study participants and study personnel knew who was getting which treatment). Several studies also showed inconsistencies in the reporting of methods, and results were imprecise.
We found four studies including 4265 pregnant women. Two of the included studies were of high quality, while the other two were of relatively low quality with limitations and biases in design and conduct. The studies were conducted in Sierra Leone, Peru and Uganda. In two studies, the women were also given a daily iron or iron-folate supplement along with antihelminthic treatment. There was no effect of antihelminthic administered in second trimester of pregnancy on maternal anaemia, low birthweight, preterm births or perinatal deaths. There was no impact on maternal anaemia in studies in which iron or iron-folate was also given to pregnant women along with antihelminthic. The impact on infant survival at six months of age could not be evaluated because data were not available. Evidence provided so far from randomised controlled trials is, therefore, insufficient to recommend use of antihelminthics for pregnant women after the first trimester of pregnancy.
In this review, we found six trials which enrolled 340 patients who had undergone surgery for borderline ovarian tumours. These trials compared the number of deaths among women who had various forms of treatment or no additional treatment after surgery. In five of the trials, the women had tumours confined to the ovaries and most were followed up for over 10 years. Only one trial enrolled women with tumours that had spread beyond the ovary, and this trial followed patients up for less than three years, which is not long enough to detect any difference between groups receiving different treatments. None of the trials found any demonstrable benefit from any of the additional forms of treatment. However, all six trials were conducted over 15 years ago and since then platinum-based chemotherapy has become widely used to treat advanced ovarian cancer. However, only one of the trials in our review assessed this more modern type of chemotherapy. Further trials of platinum-based chemotherapy and of less toxic treatments are needed, looking at the benefit of reducing the anxiety and distress of further surgery and treatment for relapse. One further trial, which recruited 32 women who had borderline ovarian tumours in both ovaries, compared conservative surgery (taking away the most diseased ovary and removing the tumour from the other ovary) with ultra-conservative surgery (removing the tumours without taking away either ovary). Nearly all the women who had ultra-conservative surgery became pregnant compared with half of those who had conservative surgery. Although about two thirds of the women in the trial developed similar tumours again, most women got pregnant before the disease recurred, all had their recurrences treated by further surgery, none developed invasive ovarian cancer nor died of their tumour. This small study suggests that ultra-conservative surgery by an experienced surgeon with careful follow up for recurrence may be recommended for women with bilateral borderline ovarian tumours who still intend to have children but, ideally, this approach should be evaluated in other independent trials. Despite rigorous searches, we did not find any trial directly comparing conservative surgery with radical surgery (surgery to remove all of the female reproductive organs) or comparing keyhole surgery (laparoscopy) with open surgery (laparotomy) for women with borderline ovarian tumours. None of these trials looked at how the various treatments affected the quality of life (QoL) of the women.
The evidence is current to 24 November 2016. We included a single randomised trial with 50 people allocated to the addition of retinoic acid after high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation, and 48 people allocated to the same treatment but without the addition of retinoic acid. The update search did not identify any new studies. Overall survival and event-free survival were no different between the two treatment alternatives. Other outcomes, including those concerning adverse events, were not adequately reported. Additional retinoic acid as part of a postconsolidation therapy after high-dose chemotherapy followed by autologous haematopoietic stem cell transplantation may not improve survival in people with high-risk neuroblastoma, and we lack information on its safety. More research is needed before we can draw solid conclusions. The evidence is based on a single study. The quality of the evidence in this single included study is low.
Three small trials of 271 babies were included in this review. The results of these studies show that it is possible to reduce the chance of serious blood infection occurring, but that almost 10 babies need to be given preventive antibiotics to avoid one case of infection. There was no difference in the likelihood of death. There were not enough data on other important effects of the antibiotics or on the possible serious side effects. There was not much similarity between the studies included in this review. Therefore, there is currently not enough evidence to recommend routinely using antibiotics in babies with central venous lines.
We identified one new study for this update. The three studies included a a total of 207 participants, which were women with breast cancer. The studies were small in size. We found no evidence of an effect for depression, stress, anxiety, fatigue, and body image. The findings of individual studies suggest that dance/movement therapy may have a beneficial effect on the quality of life, somatization (i.e. distress arising from perceptions of bodily dysfunction) and vigor of women with breast cancer. No adverse effects of dance/movement therapy interventions were reported. The evidence is based on only three small studies and the quality of the evidence is not strong. No conclusions could be drawn regarding the effect of dance/movement therapy on psychological and physical outcomes in cancer patients because of an insufficient number of studies. More research is needed. We did not identify any conflicts of interests in the included studies.
We search scientific databases for clinical trials assessing the effect of delayed (more than four days after birth) versus earlier introduction of progressive enteral feeds (where breast or formula milk is fed directly by a tube into the stomach) on the incidence of necrotising enterocolitis, death and general health in very low birth weight infants. The evidence is current to September 2014. We found nine trials with 1106 infants that assessed the effect of delayed rather than early introduction of milk feeds for very preterm or very low birth weight infants. Data from these trials did not provide any evidence that delaying enteral feeding reduces the risk of necrotising enterocolitis. The included trials were generally of reasonable methodological quality but, in common with other trials of feeding interventions in infants, it was not possible to mask carers and clinical assessors to the given treatment.
This review identified and assessed seven clinical trials that tested antibiotics in patients sick with leptospirosis. Four of these trials compared intravenous penicillin to a placebo. Three of the trials looked at differences between different antibiotics. All trials had high risk of systematic errors (bias) and of random errors (play of chance). When looked at together, these trials do not answer the basic questions about whether or not antibiotics should be used. Part of the reason for this is that there is a wide range of severity among people ill with the disease. Additional randomised clinical trials are needed. Nonetheless, these trials suggest that antibiotics administered to patients who are sick with leptospirosis may make patients feel better two days earlier than they otherwise would have improved. However, it is also possible that when patients are severely ill, penicillin therapy might increase the risk of death or dialysis in comparison to those who receive no antibiotics. Other antibiotics have not been tested in this way. Despite the lack of evidence, if a clinician chooses to treat leptospirosis with an antibiotic, there does not seem to be any difference between the appropriate use of intravenous penicillin, intravenous cephalosporin, doxycyline, or azithromycin. But, for this they have not been tested to the same extent as intravenous penicillin.
Clinical trials to test these hypotheses were performed before currently used criteria for dementia had become generally accepted. The results show improvement after the treatment with vinpocetine versus placebo, but the number of demented patients treated for at least six months was small. The available data does not demonstrate many side effect problems. Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use.
We found 11 randomised controlled trial (RCTs) from different parts of the world which recruited a total of 3673 participants overall. We judged two of the trials to be of high quality, and we graded the remainder as poor quality. This updated review provides clearer evidence that use of antibiotic eye drops can speed up the resolution of symptoms and infection, and that they are unlikely to be associated with any serious side effects.
It is known that treatment with the drug interferon clears hepatitis C virus from the blood in about 15% of patients. This review identified studies comparing ribavirin plus interferon with interferon alone in patients with chronic hepatitis C. This review shows, by combining the results from all trials, that adding ribavirin to interferon increases the number of patients who clear the hepatitis C virus to about 40% as well as the number of patients who demonstrate improved liver histology. Ribavirin and interferon may also reduce the risk of liver-related morbidity or all-cause mortality. However, the number needed to treat to prevent one patient developing morbidity or dying seems very large. Furthermore, combination therapy was associated with increased risk of anaemia and several other adverse reactions. The results gives rise to a dilemma - should we, by adding ribavirin to interferon, increase the risk of haematological, dermatological, gastrointestinal, infectious, and miscellaneous adverse reactions in a situation where it has not yet been clearly demonstrated that the antiviral effect of the intervention is directly linked to the reduction of all-cause mortality? We, therefore, suggest that the combination intervention is applied only with stringent emphasis on the individual patients' well-being. Furthermore, we suggest that all future trials within the area should focus more on adverse reactions and long-term clinical outcomes.
Overall, based on 37 studies, which included a total of 4,684,724 women, we did not find enough strong evidence suggesting a potentially higher risk of ovarian cancer in women treated with fertility drugs. A cumulative analysis of 12 case-control studies from the USA revealed increased risk of ovarian cancer in women using fertility drugs, and this risk was higher in nulliparous women (women who have not given birth) when compared to multiparous women (women who have given birth to more than one child). One of the 37 included studies reported a two-fold increase in development of serous borderline ovarian tumour in women after more than four cycles of progesterone; however the number of cases included in this group was very small. One cohort study also suggested an increased risk of borderline ovarian tumour in infertile women treated with clomiphene citrate when compared to infertile women who did not undergo treatment to conceive. Studies showing an increase in the risk of ovarian cancer were of low methodological quality, with short follow-up periods and with lack of adjustment for important confounding factors; therefore the results are too unreliable. However, compared with older studies, recent studies have tended to report both the dose and the number of cycles of infertility drugs and have included more contemporary drug regimens; this has made the final results more reliable. Infertility has been found to be an important risk factor for ovarian cancer. However, the association between infertility drugs and ovarian cancer needs to be addressed with consideration of other factors such as age, body mass index, parity, genetic factors (i.e. family history for ovarian cancer), and aetiology of the infertility, along with longer follow-up times.
This review included randomised controlled trials (RCTs) that explored oral stimulation by finger stimulation only in preterm infants. Review authors identified studies to be included by searching electronic databases, clinical trials registers, peer-reviewed journals and published conference proceedings. We included 19 studies of poor quality with small numbers of participants. Study findings suggest that oral stimulation interventions can shorten the transition to oral feeding, reduce length of hospital stay and decrease time spent on parenteral nutrition. No studies looked at longer-term outcomes of the interventions (i.e. beyond six months). Studies have reported no effect on breast feeding outcomes nor on weight gain. These studies were small and most were of low or very low methodological quality. Review authors identified no high-quality studies that could support the efficacy, effectiveness and safety of oral stimulation interventions. Larger, well-designed RCTs are needed to help inform parents and caregivers about the possible benefits and harms of this intervention.
We searched several important medical databases in April 2016, as well as trial registers, conference proceedings and reference lists. We found only one relevant medical study in which the children participating were allocated randomly to different treatments. The study compared treatments in which the simple bone cysts were injected with bone marrow or steroid (methylprednisolone acetate). Ninety children with an average age of 9.5 years participated in this study. Results were available for 77 children. Two years after treatment, X-ray examination showed that successful healing of bone cysts was more common in children who had received steroid injections; however, we are very uncertain whether this is a true finding. Low quality evidence two years after treatment showed children in the two treatment groups had similar high levels of function (measured by the Activity Scale for Kids score) and low levels of pain (measured by Oucher score). There was very low quality evidence that there was no difference between the two interventions for adverse events, including pathological fracture after treatment. As the quality of the evidence is low, or very low, we cannot definitively conclude that there are no differences between the treatments, and we do not know whether either treatment gives better results with fewer complications. This review is based on one trial with a small number of participants. Hence, at present there is insufficient evidence to determine the best method for treating simple bone cysts in the long bones of children. More studies with larger numbers of participants and that monitor children for longer follow-up periods are needed.
This review provides evidence that group-based parenting programmes improve childhood behaviour problems and the development of positive parenting skills in the short-term, whilst also reducing parental anxiety, stress and depression. Evidence for the longer-term effects of these programmes is unavailable. These group-based parenting programmes achieve good results at a cost of approximately $2500 (£1712 or €2217) per family. These costs are modest when compared with the long-term social, educational and legal costs associated with childhood conduct problems.
The aim of this review was to see how effective palliative care interventions in care homes are, and to describe the outcome measures used in the studies. We found only three suitable studies (735 participants), all from the USA. There was little evidence that interventions to improve palliative care for older people in care homes improved outcomes for residents. One study found that palliative care increased bereaved family members' perceptions of the quality of care and another found lower discomfort for residents with dementia who were dying. There were problems with both of these findings. Two studies found that palliative care improved some of the ways in which care was given in the care home, however, we do not know if this resulted in better outcomes for residents. There is a need for more high quality research, particularly outside the USA.
This review summarised and meta-analysed the evidence from randomised clinical trials on the effect of prostaglandins for adult liver transplanted patients. We found ten trials randomising 652 patients. Evidence from these trials is inconclusive on the role of prostaglandins regarding outcomes such as death or liver re-transplantation. The risk of acute kidney failure requiring dialysis may be reduced by two thirds if a liver transplant patient receives prostaglandins, although the level of evidence is only moderate due to risks of systematic errors (bias) and random errors (play of chance). No severe adverse events are reported. Therefore, further randomised trials with low risk of bias and sufficient sample sizes are still needed to establish whether prostaglandins should be administered for liver transplanted patients.
We searched for evidence from randomised controlled trials in September 2017. We identified eight studies with a total of 2227 women undergoing elective (planned) caesarean section before the onset of labour. Of these women, 1097 underwent cervical dilatation with a double-gloved index finger, or in one study with a Hegar dilator, during surgery, while 1130 did not undergo cervical dilatation during surgery. Low- or very low-quality evidence suggested it was unclear whether cervical dilatation had any impact on postpartum haemorrhage (estimated blood loss greater than 1000 mL), the need for blood transfusion, and other measures of blood loss, postpartum haemorrhage within six weeks, febrile morbidity (infection indicated by increased temperature over a defined time period), endometritis (infection of the lining of the womb), or uterine subinvolution (uterus not returning to its normal size after childbirth). There were no data for cervical trauma. We found a slight improvement with mechanical dilatation for some outcomes that had not been specified in our original protocol, but the evidence for these outcomes was based on one or two studies (mean blood loss, endometrial cavity thickness, retained products of conception, distortion of uterine incision, and healing ratio). Cervical dilatation did not have a clear effect on other secondary outcomes, (again not specified in our original protocol): wound infection, urinary tract infection, operative time, infectious morbidity, and integrity of uterine scar. It is uncertain whether cervical dilatation has any impact on reducing postoperative problems after caesarean section. This means there is insufficient evidence to encourage or discourage the use of mechanical dilatation of the cervix at elective caesarean section for reducing postoperative ill-health.
Study characteristics In November 2017 we searched for clinical trials that used cannabis products to treat conditions with chronic neuropathic pain in adults. We found 16 studies involving 1750 people. Studies lasted 2 to 26 weeks. Studies compared different cannabis-based medicines. Ten studies compared an oromucosal (mouth) spray with a plant-derived combination of tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, and cannabidiol (CBD), an anti-inflammatory ingredient of cannabis, against a fake medication (placebo). Two studies each compared inhaled herbal cannabis and cannabis plant-derived THC with placebo, and one study compared a man-made cannabinoid mimicking the effects of THC (nabilone) with placebo. One study compared nabilone with a pain killer (dihydrocodeine). We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. There was no high-quality evidence. All cannabis-based medicines pooled together were better than placebo for the outcomes substantial and moderate pain relief and global improvement. All cannabis-based medicines pooled together were better than placebo in reducing pain intensity, sleep problems and psychological distress (very low- to moderate-quality evidence). There was no difference between all cannabis-based medicines pooled together and placebo in improving health-related quality of life, stopping the medication because it was not effective, and in the frequency of serious side effects (low-quality evidence). More people reported sleepiness, dizziness and mental problems (e.g. confusion) with all cannabis-based medicines pooled together than with placebo (low-quality evidence). There was moderate-quality evidence that more people dropped out due to side effects with cannabis-based medicines than with placebo. Herbal cannabis was not different from placebo in reducing pain and the number of people who dropped out due to side effects (very low-quality evidence).
We included three studies on a total of 13,885 participants (9640 children and 4245 adults) and 1200 households in Nicaragua and Niger. They examined five programmes by governmental, non-governmental or research organisations that gave recipients cash handouts worth USD 145 to USD 250 (or more, depending on household characteristics) as part of a disaster response (in these cases, to droughts). The studies had some serious methodological limitations, so we considered the evidence to be of very low quality and very uncertain. UCTs appeared to contribute to a very small increase in the proportion of children who received vitamin or iron supplements and a beneficial effect on children's home environment. They may have resulted in a very large reduction in the chance of dying, a moderate reduction in the number of days spent sick in bed, and a large reduction in children's risk of acute malnutrition. UCTs had no clear effect on the proportion of children who received deworming drugs, children's height for age, adults' level of depression, or the quality of parenting behaviour. No adverse effects were identified.The included studies did not examine several important outcomes, including food security and equity impacts. Compared with grants of food, there was no evidence that a UCT influenced the chance of child death or severe acute malnutrition. Compared with the same UCT paid via mobile phone, a UCT paid in-hand led to a moderate increase in household dietary diversity, but there was no evidence for any effect on social determinants of health, health service expenditure, or local markets and infrastructure. Additional research is required to reach clear conclusions regarding the effectiveness and relative effectiveness of UCTs in improving health services use and health outcomes in humanitarian disasters in LMICs.
After searching for all relevant studies up to May 2015, we found 13 studies (14 articles) that met our inclusion criteria. However, only three compared different operation types. The others compared aspects of one operation type. One study presented early and late outcomes. What happens to people with Dupuytren’s disease up to five weeks after needle fasciotomy compared with fasciectomy? • Hand function may be slightly better after needle fasciotomy than after fasciectomy (low-quality evidence). • People who have had needle fasciotomy may be more satisfied than those who have had fasciectomy (low-quality evidence). • Fasciectomy probably straightens fingers better than needle fasciotomy in people with advanced disease, but probably no difference is apparent in people with milder disease (low-quality evidence). • A feeling of tingling in the fingers is probably more common after fasciectomy than after needle fasciotomy during the first week after treatment (low-quality evidence). What happens to people with Dupuytren’s disease five years after needle fasciotomy compared with fasciectomy? • Satisfaction may be better after fasciectomy than after needle fasciotomy (low-quality evidence). • Recurrence may be more common after needle fasciotomy than after fasciectomy (low-quality evidence). What happens to people with Dupuytren’s disease up to 36 months after z-plasty closure of a limited fasciectomy compared with use of small ‘firebreak’ skin grafts (a form of dermofasciectomy)? • Little or no difference in outcomes is likely between patients who had z-plasty and those who had small skin grafts, although skin graft procedures take longer to perform (low-quality evidence). What happens to people with Dupuytren’s disease who wear a splint at night after surgery? • Wearing a splint at night after surgery probably does not help to straighten fingers nor to improve hand function, and it may slightly worsen the patient's ability to make a full fist (low-quality evidence). Reporting of complications was variable. We often do not have precise information about side effects and complications, particularly rare but serious side effects. Side effects may include altered feeling in the fingers or reduced ability to make a full fist. Rare complications may include injury to the tendons that pull the fingers into the palm.
We searched for all published Cochrane Reviews of MS clinical trials that evaluated the effectiveness of rehabilitation interventions compared with various control groups (no intervention or different type of intervention). We evaluated all relevant reviews, and summarised the findings. We included a total of 15 Cochrane Reviews, which included 168 clinical trials, and a total of 10,396 people with MS. These good-quality reviews evaluated a range of rehabilitation interventions, including: physical activity and exercise therapy, hyperbaric oxygen therapy, whole-body vibration, occupational therapy, cognitive and psychological interventions, nutritional and dietary supplements, vocational rehabilitation, information provision, telerehabilitation, and interventions for the management of spasticity. The findings showed some benefits for people with MS who participated in exercise and physical activity programmes or multidisciplinary rehabilitation programmes (where the intervention is provided by a team of health professionals from different professions). They found improvements in everyday activities, function, and health-related quality of life, compared with those who were not offered rehabilitation. Evidence for other rehabilitation modalities was limited, due to lack of good-quality studies. More research is needed to determine whether various types of rehabilitation modalities are effective in reducing disability in people with MS.
We identified a broad range of studies of different types of preparations used at different dosages in both adults and children. The evidence is current up to March 2014. We found no good evidence for or against the effectiveness of OTC medications in acute cough. Nineteen studies reported adverse effects of these medications and described infrequent, mainly minor side effects such as nausea, vomiting, headache and drowsiness. The results of this review have to be interpreted with caution because the number of studies in each category of cough preparations was small. Many studies were poorly reported making assessment of risk of bias difficult. While all studies were placebo-controlled randomised controlled trials only a minority reported their methods of allocation and randomisation and there was lack of reporting of blinding of outcome assessors and whether cough outcome measures were validated. In addition, studies supported by pharmaceutical companies or other providers were more likely to have positive results. Studies were very different from each other in terms of treatment types, treatment duration and outcomes measured, making evaluation of overall effectiveness of OTC cough medicines difficult.
The review authors searched the medical literature and were able to find only one small randomised controlled trial. The 14 infants included in the trial had a birthweight over 2000 g and were enrolled at a mean age of 10 hours. They had received ventilatory support and fluid expansion after birth. Infants treated with low dose dopamine (2.5 microg/kg/min) did not differ from the infants receiving placebo (dextrose water) in the number who died before discharge from hospital. Neurodevelopmental disability was similar in both groups, in all infants randomised and in survivors. The timing of assessments was variable. These findings are limited with only one small study in which three of 12 survivors were lost to follow up.
The two studies included in this review randomly assigned 305 women being treated with clomiphene citrate to help eggs to develop to additionally receive a medicine (urinary hCG) to trigger their release or to receive no additional treatment. We found no trials comparing other ovulation triggers given with other medicines used for ovulation induction. The evidence is current to November 2013. Giving women on clomiphene citrate additional urinary hCG may not increase their chances of delivering live babies, ovulating or becoming pregnant. Multiple pregnancies, miscarriages and preterm deliveries were not more common with or without an ovulation trigger. No serious adverse events were reported in either study. We cannot be certain whether ovulation triggers are better or worse than no ovulation triggers in women undergoing ovulation induction because not enough women were included in the two trials for definite results to be obtained. Larger trials in women undergoing ovulation induction that compare different ovulation triggers versus no additional treatment are needed.
No studies on antibiotics, pneumococcal vaccination and any other non-drug prophylaxis were identified. This review found that intravenous immunoglobulin (IVIG), thymosin, oral transfer factor, Bacillus Calmette-Guerin (BCG) vaccine injection and two kinds of Chinese medicinal herbs (Huangqi granules and TIAOJINING) may help prevent infections in nephrotic children. These studies were methodologically poor. Currently there is no strong evidence for recommending any interventions for preventing infections in nephrotic syndrome. More research is needed.
We included 7 trials, with a total of 249 participants, covering 6 treatments in this review. Topical clobetasol propionate and mometasone furoate were effective in treating genital lichen sclerosus. There was no substantial difference in the efficacy of relieving symptoms (e.g. itching and pain) between pimecrolimus cream and clobetasol propionate, but the former was less effective in improving gross appearance. More research is needed for a number of reasons: to decide the strength of steroids that should be used, as well as the frequency and length of application to the skin which gives the best results; to examine other skin treatments; to assess the long-term benefits of topical treatments with regard to relieving symptoms and reducing the risk of developing genital cancers; and to examine the benefits of treatments on the quality of the sex lives of people with this condition.
Review authors identified 28 randomized controlled trials involving 3497 critically ill patients with circulatory failure, among whom 1773 died. Patients were followed up to one year. The following drugs, given alone or in combination, were studied in 12 different comparisons: dopamine, norepinephrine, epinephrine, phenylephrine, vasopressin, and terlipressin. In summary, researchers found no significant differences in risk of dying in any comparisons of different drugs given alone or in combination when latest reported death was considered. Disturbances in the rhythm of the heart were observed more frequently in people treated with dopamine than in those treated with norepinephrine. The quality of the evidence was high for the comparison of norepinephrine and dopamine, and was very low to moderate for the other comparisons. Findings were consistent among the few large studies and studies of different quality.
Transcutaneous electrical nerve stimulation (TENS) is rarely used for the treatment of dementia but has been studied in a number of randomized controlled trials. Although the available data suggests TENS may be beneficial for some neuropsychological and/or behavioural aspects of dementia insufficient data was available to these reviewers for definitive conclusions to be drawn.
The review shows that artemisinin drugs clear malaria parasites from the blood more effectively than standard treatment drugs. In areas where malaria parasites are more resistant to existing drugs, such as South-East Asia, artemisinin drugs are not better at sustained parasite clearance than standard treatment with quinine or mefloquine. Combination treatment using an artemisinin drug together with the longer-acting antimalarial drug mefloquine improves sustained clearance of parasites, but mefloquine is associated with adverse effects. There are few studies on combination treatment with longer-acting antimalarial drugs that are safer than mefloquine. There is no evidence from trials that any of the several artemisinin derivatives is better than the others.
We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of dietary fibre intake in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes). The evidence is current to January 2015. Twenty three trials fulfilled our inclusion criteria. All of the trials were short term and so could not examine the effect of fibre intake on CVD events. All of the trials examined the effects of fibre intake on lipid levels (lipids are fat-like substances, including cholesterol found in the blood), blood pressure or both. Pooling the results showed a beneficial reduction in total cholesterol and LDL cholesterol (sometimes called 'bad' cholesterol), and diastolic blood pressure with increasing fibre intake. There were no clear patterns for the type of fibre used (soluble or insoluble fibre) or the way in which fibre was provided (via supplements or food stuffs) but their were few studies in each group so results are uncertain. Overall the risk of bias was unclear with few studies judged to be at low risk of bias (so less chance of arriving at the wrong conclusions because of favouritism by the participants or researchers), and for some there was a high risk of bias for some of the quality criteria. The results of this review need to be interpreted cautiously bearing this in mind. There is a need for longer-term well-conducted RCTs to determine the effects of fibre intake on CVD events and to further explore effects by the type of fibre and the way in which increased fibre is provided.
The authors found 56 studies; the overall findings show that school-based secondary prevention programmes aimed at reducing aggressive behaviour do appear to produce improvements in behaviour. The improvements can be achieved in both primary and secondary school age groups and in both mixed sex groups and boy-only groups. Further research is needed to investigate if the apparent beneficial programmes effects can be realised outside the experimental setting and in settings other than schools. None of the studies collected data on violent injury, so we can not be certain of the extent to which an improvement in behaviour translates to an actual injury reduction. In addition, more research is needed to determine if the beneficial effects can be maintained over time, and if the benefits can be justified against the costs of implementing such programmes.
We searched for evidence on 31 January 2016 and found one small randomised controlled trial (abstract only) that was of poor quality and involved 180 women from Canada.The trial compared two blood sugar ranges, one strict the other more liberal, and reported a very few health outcomes for the pregnant woman and her baby. The trial did not provide any data for this review's main outcomes. For the woman, these related to the development of high blood pressure and protein in the urine during pregnancy, developing type 2 diabetes. For the baby, these outcomes related to death of the baby, increased birthweight, increased risk of birth trauma because of their size, and disability. More women were on insulin in the strictly controlled group (but this result is based on very low quality evidence). No clear differences were reported for caesarian section rates. No other secondary outcome data for women with GDM relevant to this review were reported. No differences were reported for the number of babies that had a birthweight greater than 4000 g or were small-for-gestational age. No other secondary outcomes for the babies relevant to this review were reported.The study did not report on adverse events. This review found that there is not yet enough evidence from randomised controlled trials to determine the best blood sugar range for improving health for pregnant women with GDM and their babies. Four studies are ongoing but not yet complete. More high-quality studies are needed that compare different targets for blood sugar levels and assess both short-term and long-term health outcomes for women and their babies to guide treatment. Studies should include women's experiences and assess health services costs.
We found 32 studies that tested the effects of increased police patrols on traffic deaths, injuries, and crashes. There was one randomized controlled trial and no quasi-randomized controlled trials. Almost all of the programs included additional interventions like community information programs, media campaigns, and special training for police officers. Most studies found that increased police patrols reduced traffic crashes and fatalities. Evidence for the effect on traffic injuries was less consistent. The detail provided on the methodology of included studies was almost uniformly poor. When this information was reported, the methodological quality was often weak. Therefore, the available evidence does not firmly establish that increased police patrols reduce the adverse consequences of alcohol-impaired driving. Good quality controlled studies with adequate sample size are needed to evaluate increased patrols. Also needed are studies assessing the cost-effectiveness of this intervention.
Six studies involving a total of 610 patients matched the inclusion criteria for this review. Four evaluated three tricyclic antidepressant agents (amitriptyline, nortriptyline and trimipramine) for the treatment of tinnitus. These studies did not find enough evidence to prove the efficacy of these agents in the management of tinnitus. One study evaluated paroxetine, a selective serotonin reuptake inhibitor antidepressant, and one evaluated trazodone, an atypical antidepressant. Neither of these studies showed benefit of paroxetine or trazodone in the treatment of tinnitus. Side effects, though relatively minor, were common in all groups of antidepressants. Further research is required.
There are many types of dressings that can be used, which also vary considerably in cost.This review (four studies involving a total of 511 participants) identified no research evidence to suggest that any type of hydrocolloid wound dressing is more effective in healing diabetic foot ulcers than other types of dressing.
We examined the research published to 7 August 2017. We found three clinical trials recruiting 366 preterm babies. All three studies reported on preventing severe stages of retinopathy. We found that orally administered beta-blockers may offer short-term benefits such as lower risk of progression to a more severe stage of retinopathy and less need for additional treatment. However, there were no data on long-term vision; and studies did not show an effect of beta-blockers on the most severe stages of retinopathy. On the other hand, serious adverse effects of beta-blockers were reported in one of three studies. The overall quality of evidence for outcomes in this review varied from low to moderate. Thus, our confidence in the results of this review is very limited. We cannot recommend routine use of beta-blockers for prevention or treatment of ROP in preterm infants. Future high-quality studies are necessary to determine whether benefits of beta-blockers outweigh their risks in preventing or treating ROP in preterm infants.
Nine studies, involving 8228 women, were included in this review. Most of the women in the studies (91%) had tumours 3 cm or less in size, all had complete removal of the tumour on pathology and 68% had no evidence of cancer in their lymph nodes. Where the breast size was known, 83% had small or medium breasts. The evidence is current up to May 2015. Local recurrence was not different for women having fewer treatments (four fewer local relapses per 1000 (where the true value may be anywhere between 16 fewer to 10 more local relapses per 1000)). Breast appearance was not different for women undergoing fewer treatments (31 fewer fair/poor breast appearance per 1000 (where the true value may be anywhere between 59 fewer to 3 more per 1000 with fair/poor breast appearance)). Survival was not altered by having fewer treatments (13 fewer deaths per 1000 (where the true value could be between 31 fewer to 5 more deaths per 1000)) and there was no significant difference in late skin toxicity (4 more episodes of toxicity per 1000; where the true value may be anywhere between 14 fewer to 36 more episodes of toxicity per 1000) or radiation toxicity. Acute skin toxicity is decreased with fewer treatments (326 fewer events per 1000 (where the true value may be anywhere between 264 fewer to 374 fewer acute skin toxicity events per 1000)). This review indicates that for women who fit these criteria, using fewer radiation treatments after tumour removal gives the same cancer control, with less skin reaction at the time and the likely the same side-effects in the long term. We found high quality evidence for the following outcomes: local recurrence-free survival, breast appearance, toxicity, overall survival and breast cancer-specific survival. We found moderate quality evidence for relapse-free survival, and no data for mastectomy rate (mastectomy may be required because of local recurrence or unacceptable treatment-related toxicity) or costs.
We identified nine clinical trials to October 2015, which all investigated some form of caregiver-mediated exercises compared with usual care, no treatment (intervention), or another intervention that was not caregiver-mediated. We included 333 patient-caregiver couples in the review. We found trials in which caregiver-mediated exercises themselves were the studied subject (called CME-core). In addition, we found trials in which the caregiver was the provider of another, already existing intervention. In the latter category, it was difficult to separate the effect of caregiver-mediated exercises from the effect of the other intervention. We found evidence that caregiver-mediated exercises could have a positive effect on patients' standing balance (low-quality evidence) and quality of life (very low-quality evidence) directly after the intervention. In the long term, we found very low-quality evidence for a positive effect on walking distance. For speed of use of the arm and hand, we found low-quality evidence in favour of the control group. We found no significant side effects or beneficial effects on caregiver strain; we judged the quality of this evidence as moderate (after intervention) to very low (long term). Furthermore, we found no significant effects for basic activities of daily living, such as dressing and bathing, after intervention (moderate-quality evidence) or follow-up (low-quality evidence). In addition, we found no significant effects for extended activities of daily living, such as cooking and gardening, after intervention or at follow-up (both low-quality evidence). In the CME-core analysis, we found moderate-quality evidence for a positive effect of caregiver-mediated exercises for basic activities of daily living. It can be concluded that caregiver-mediated exercises may be a promising form of therapy to add to usual care. The number of included trials was small and the level of evidence was of very low to moderate quality. Therefore, results should be interpreted with caution.
We identified results from three randomized controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) to determine whether glasses were successful in reducing the occurrence of strabismus in far-sighted infants. The trials enrolled infants ages 12 months or younger and measured outcomes between the ages of three and four years. The three trials enrolled 855 infants and included about 79% of the infants in the final analyses of different outcomes. These trials were all conducted in the UK with follow-up periods ranging from one to 3.5 years. The evidence is current up to April 2014. Combining the results of the three trials, we found the risk of strabismus with wearing glasses is uncertain. We identified several potential biases in the way these three trials were conducted. Given the high risk of bias and amount of missing data, it is possible the observed decrease in risk of developing strabismus may be an overestimate of the true effect. The evidence does not currently support the conclusion that glasses prevent strabismus in far-sighted children. More research is required to answer the question. In addition, the prescription of glasses, particularly glasses that correct all of the prescription (full correction), may prevent eyes from developing naturally and normalizing to clear visual acuity. Emmetropization (normalization of vision which usually occurs during the natural growth process) was reported in two trials: one trial suggested that spectacles impede emmetropization, and the second trial reported no difference in the rate of refractive error change. The overall quality of the evidence was very low, particularly due to improper trial design, incomplete outcome data, and the lack of power to provide an accurate estimate of the overall treatment effect of spectacle correction for preventing strabismus.
Three trials have compared ropinirole with an inactive placebo in 263 patients in the later stages of Parkinson's disease. Two studies were relatively small, were conducted over the short term (12 weeks), and used relatively low doses of ropinirole (maximum allowed 8 and 10 mg/d) in a twice daily administration regime. For these reasons, the results of these trials have not been included in a statistical overview. The other study was medium term (26 weeks) and used ropinirole doses in line with the current UK licensed maximum (24 mg/d) in a three times a day regime. The conclusions of this review are based on this single trial and thus should be viewed with some caution. No clear difference in the time patients spent in the immobile off state was found between ropinirole and placebo. However, this was probably due to there being too few patients in the trial. Measurements of physical difficulties and problems with activities of daily living (such as bathing, shopping, etc.) were poor in these studies with incomplete information available. Levodopa dose reduction was greater with ropinirole than placebo by 180 mg/d. However, dyskinesia was increased in those who received ropinirole (2.9 times more common with ropinirole than placebo). No other differences in side effects or withdrawals from treatment were found. Ropinirole reduces levodopa dose but at the expense of increased dyskinetic side effects. No clear effect on off time reduction was found in this single trial. Side effects were similar with ropinirole and placebo. These conclusions apply to short and medium term treatment, up to 26 weeks. Further longer term trials are required, with measurements of quality of life and costs, and also studies to compare the newer with the older dopamine agonists.
This review aims to examine the effectiveness and safety of these three instruments. The findings showed that UCS results in less blood loss when compared to MES. Operating time was shorter when EBVS was used compared to MES. No marked difference was observed between UCS and EBVS. No difference in complications between all three instruments were reported in the findings. However, it is recognised that more trials are needed to support the evidence provided in this report.
This review included seven randomised controlled trials with a total of 266 participants. Four trials studied the effects of non-steroidal anti-inflammatory agents (NSAIDs) in chronic CMO while the other three examined the effect of NSAIDs in acute CMO. This review found two trials which showed that topical NSAID (0.5% ketorolac tromethamine ophthalmic solution) has a positive effect on chronic CMO and a third trial which was supportive of this finding (albeit not statistically significantly so). One study suggested no effect and our review suggests further work is needed for a more conclusive decision regarding use of NSAIDS in chronic CMO. Similarly, the effects of NSAIDs in acute CMO remain unclear and this too needs further investigation.
We include 41 full-text peer-reviewed studies of either structured telephone support or home telemonitoring in this review. Twenty-five studies evaluate structured telephone support (eight new studies, plus one previously included study now classified as telemonitoring; total of 9332 participants), 18 evaluated telemonitoring (nine new studies; total of 3860 participants) and two studies evaluated both interventions (included in listed counts). This review demonstrates that supporting people with heart failure at home using information technology can reduce the rates of death and heart failure-related hospitalisation. It can improve people's quality of life and knowledge about heart failure and self care. Most patients, even those who are elderly, learn to use the technology easily and are satisfied with these interventions. We assessed the quality of the evidence for the primary outcomes in this review (all-cause mortality, all-cause hospitalisation and heart failure-related hospitalisation) according to GRADE criteria. We rated it from very low (all-cause hospitalisations) to moderate (all-cause mortality and heart failure-related hospitalisations).
Although complex laboratory studies show that ion generators alter airways function, the few studies which have been conducted in the homes of people with asthma, demonstrate no significant benefit in improving lung function or symptoms.
Data from one quasi-randomised trial with 88 infants from 75 families were included in the review. Infants in the early discharge programme with home gavage feeds had a mean hospital stay that was approximately nine days shorter than that of infants in the control group. Infants in the early discharge programme also had lower risk of clinical infection during the home gavage period compared with infants in the control group during the corresponding time in hospital. No significant differences were observed between groups in duration and extent of breast feeding, weight gain, re-admission within the first 12 months post discharge from the home gavage programme or from hospital, scores reflecting parental satisfaction or health service use. Evidence is needed regarding the effects of early home discharge for preterm babies who are stable but still need gavage (tube) feeds.
In this review, existing evidence comparing the health outcomes between treated and untreated individuals are summarized. Available data from the limited number of available trials and participants showed no difference between treated and untreated individuals in heart attack, stroke, and death. About 9% of patients treated with drugs discontinued treatment due to adverse effects. Therefore, the benefits and harms of antihypertensive drug therapy in this population need to be investigated by further research.
We did a computer search for studies of pills with three phases versus pills with one phase in May 2011. We also wrote to researchers and manufacturers to find other trials. We included randomized trials in any language. The studies had to follow women for at least three treatment cycles. We found 23 trials that looked at three-phase versus one-phase birth control pills. Many studies did not have good methods and the authors did not always report all their methods. The two types of pills did not differ in the numbers of women who got pregnant. About half of the trials found better bleeding patterns with the three-phase pill. The numbers of women who stopped using the pills were about the same for both types of pills. The evidence was not strong enough to say whether the three-phase pill was better than the one-phase pill for pregnancy prevention, bleeding patterns, or continued use. Therefore, we recommend one-phase pills for women starting to use birth control pills. Large trials that are of good quality are needed to see if pills with three phases work better than those with one phase.
A former Cochrane review published in 2004 found some evidence of a possible benefit of using oral Chinese herbal medicine (CHM) for eczema; however, the results from only 4 included studies were inconclusive and need to be updated (those four studies have not been included in this update as they investigated a product that has been withdrawn from the market since 2004). As well as updating that review, we have also widened the scope of the review to assess the effects of topical CHM for eczema. We wrote a new protocol to expand the scope of this review. This review included 28 randomised controlled trials (RCTs), with 2306 children and adults, of which 4 compared CHM to placebo, 22 to conventional medications, and 2 to CHM taken by mouth. Most of the included studies reported a higher number of participants who had recovered and significantly improved, with less itching in the CHM groups than the control groups. Where CHM was compared to conventional drugs, although the total effectiveness rate outcome was superior with CHM, it was based on very low quality evidence. One study reported that the quality of life (QoL) score in the CHM group was better than in the placebo group after using a CHM formula taken by mouth for 12 weeks. We assessed most of the studies as at high 'risk of bias' and therefore not of good quality, and there was substantial inconsistency between the studies, so any positive effect in CHM must be treated with caution. One study reported one severe adverse event. Minor adverse events were observed in 24 studies, including temporary elevation of enzymes in 3 cases, which was reversed soon after stopping CHM. Eight included studies received government funding. We could not find conclusive evidence that CHM taken by mouth or applied to the skin was of benefit to children or adults with eczema. Well-designed, adequately powered RCTs are needed to evaluate the efficacy and safety of CHM for eczema.
We searched the medical literature until May 2014 and found two relevant studies that included a total of 94 adults with cervical spine facet dislocations. One trial included individuals with spinal cord injuries and the other included individuals without spinal cord injuries. Both studies compared the anterior versus posterior surgical approach. Quality of the evidence  The two studies were small and both were at high risk of bias. We therefore judged the quality of the evidence to be very low. Summary of the evidence  Neither study found differences between the two approaches in neurological status and pain at one year. One study also found no differences between the two approaches in patient-reported quality of life. Although one study found that the anterior approach resulted in more normal curvature of the neck, the other study reported finding no difference between the two approaches with regard to the alignment of the neck vertebrae. The evidence was insufficient to indicate differences between the two approaches in medical adverse events, rates of instrumentation failure and infection. Although over half (11) of 20 people in the anterior approach group in one study had voice and swallowing disorders, these all resolved by three months. Conclusion  The quality of the evidence was very low, meaning that we are very uncertain about the direction and size of effect. Thus we are unable to say whether either an anterior or posterior approach to the surgical management of individuals with dislocations to the cervical spine facet joints is better than the other. We suggest that further research is needed to inform the choice of surgical approach.
After searching for all relevant studies (until 14 April 2016), we found one study in which a subgroup of 227 people with AAA received either the beta-blocker metoprolol (medication that reduces blood pressure) or a placebo (dummy treatment). This study's results were imprecise for all causes of death and death from cardiovascular disease or nonfatal cardiovascular events at 30 days or six months after AAA repair. Side effects from the drug were reported for the whole study population and were not available for the subgroup of participants with AAA. We judged this study to be at a generally low risk of bias. We graded the quality of the evidence to low as we only included one small sized study in the review, there were few events reported and the result was consistent with benefit and harm. Larger and longer studies are needed to find out which treatment is most effective. At present, people with AAA are offered a wide range of pharmacological treatment including antiplatelet drugs, antihypertensives and lipid-lowering drugs. Future trials should test available drugs to find the most effective strategy, whether that be one single drug or a combination of treatments. In addition, the acceptability of such interventions needs to be assessed and future studies should measure adverse side effects associated with these drugs and their impact on quality of life.
Four trials met the inclusion criteria. They included a total of 104 people; however, three trials did not provide results that we could include in the review. (One trial studied different kinds of foot orthoses, which are in-shoe devices that redistribute force and change gait), and two investigated the effects of adding botulinum toxin injections to various treatments such as stretching, exercises, splints, and footwear.) This review therefore only included the results of one trial, in which 47 children (aged between 5 and 14.5 years) received treatment with either plaster casts alone or plaster casts and injections of botulinum toxin A (BTX) into calf muscles. The study reported how much the children toe walked (based on their parents' observation), any change in ankle range of movement, and relapse (whether the children were still toe walking 12 months after treatment). The included study took place in Sweden and was not funded by anyone with a commercial interest in the results of the study. The evidence was too uncertain to determine whether or not there were differences in outcomes (amount of toe walking observed by parents, range of movement at the ankle, or recurrence of toe walking at 12 months) between children who received plaster casts and injections of BTX into calf muscles, compared to those who received plaster casts alone. There were small numbers of adverse events in both groups, including calf pain and minor skin problems during treatment. The available evidence is too uncertain to determine whether treatment with BTX injections and plaster casts are any more effective than just plaster casts in children with toe walking not associated with a medical condition. The limited evidence found in this review indicates a need for future research on treatments for this condition.
We found 15 randomized controlled trials, conducted primarily in North America and Europe, to investigate the effects of methods to lower blood pressure (drug-based in 14 trials; lifestyle change in 1 trial) in 4157 type 1 and 9512 type 2 diabetics, ranging from 16 to 2130 participants in individual trials. The follow-up period ranged from one to nine years for included trials. Of the 15 trials, six were funded in full by one or more drug companies. Seven more studies received drug company support, usually in the form of study medications. The remaining two studies were conducted with support from government-sponsored grants and institutional support. The evidence is current to April 2014. Overall, the included trials provided modest support for lowering blood pressure to prevent diabetic retinopathy, regardless of diabetes type or baseline blood pressure level. However, the evidence did not indicate that lowering blood pressure kept diabetic retinopathy from worsening once it had developed or that it prevented advanced stages of diabetic retinopathy that required laser or other treatment of affected eyes. Treatment to reduce the blood pressure of people with diabetes is warranted for other health reasons, but the available evidence does not justify reduction of blood pressure solely to prevent or slow diabetic retinopathy. Overall, the quality of the evidence was low to moderate based on the reported information. The quality was downgraded mainly because some studies did not report outcomes for all or most participants at follow-up time points, and results from different studies were not highly consistent.
No studies comparing vitamin A or other retinoid supplements to placebo (dummy drug containing no vitamin A) were included, but we did find one study comparing beta-carotene supplementation (a precursor of vitamin A) to placebo. A total of 24 people with cystic fibrosis (aged 6.7 to 27.7 years) were put into groups at random and treated either with β-carotene capsules (at a high dose for three months followed by a low dose for a further three months) or with placebo (for six months). No studies on vitamin A supplementation were included in this review. The single included study revealed that high-dose beta-carotene supplementation for three months led to fewer days on which people with CF required antibiotics compared to placebo, but this was not the case in the following three-month section of the study when low-dose beta-carotene supplementation was compared to placebo. Other clinical outcome measures (growth, nutritional status and lung function) showed no statistical significant differences between treatment and placebo groups. No side effects were observed. The other outcomes in this review, such as vitamin A deficiency symptoms, mortality, toxicity and quality of life, were not reported. We could only include one study in this review and that study had several limitations. This is reflected in the assessment of low-quality evidence, judged using the specific evidence grading system (GRADE). So, we feel that the strength of evidence is low. Not all outcome measures were reported after each supplementation dose and results should be viewed with some caution as some beta-carotene from the high-dose period was probably still present in the blood during the low-dose supplementation period. Since no studies on vitamin A supplementation were included in the review, no conclusions can be drawn regarding the routine use of vitamin A supplements. Due to limitations of the included study of beta-carotene supplementation, no definitive conclusions regarding its use can be drawn either. Until further evidence is available, local guidelines should be followed regarding supplementation.
We examined the evidence published up to 18 March 2016 and included nine trials with 1337 people that evaluated either dexamethasone, methylprednisolone, or prednisolone given in addition to antituberculous drugs; one trial was of high quality, while the other trials had uncertainties over study quality due to incomplete reporting. The analysis shows that corticosteroids reduce the risk of death by a quarter at two months to two years after treatment was started (high quality evidence). Corticosteroids make little or no difference to the number of people who survive TB meningitis with brain damage causing disability (low quality evidence); because this event is uncommon, even taking the most pessimistic estimate from the analysis of a slight increased risk with corticosteroids means this would not be quantitatively important when compared to the reduction in deaths. One trial followed up participants for five years, by which time there was no difference in the effect on death between the two groups, although the reason for this change over time is unknown. Only one trial evaluated the effects of corticosteroids in human immunodeficiency virus (HIV)-positive people but the number is small so we are not sure if the benefits in terms of fewer deaths are preserved in this group of patients.
We identified six randomised controlled trials that reported one or more of the outcomes we thought were important. There may have been flaws in trial conduct that could produce incorrect results. The six trials that provided data for this review included 815 participants (410 participants had subcutaneous closure of incisions and 405 participants did not). In the trials that reported the outcomes, overall 7% of participants developed superficial wound infection, 8% of participants developed superficial separation of wounds, and 8% of participants developed deeper separation of layers in both the groups but there was no clear evidence of a difference in incidence between the subcutaneous closure group and the no subcutaneous closure group. There was no clear evidence of a difference in the length of hospital stay between the groups. We do not know whether these results indicate that there is really no difference between subcutaneous closure and no subcutaneous closure, or that there are problems with study design that make it difficult to identify true differences between the two techniques. So significant benefits or harms of subcutaneous closure cannot be ruled out. Furthermore, no trial assessed the impact of subcutaneous closure on quality of life, long-term patient outcomes (trial follow-up periods varied between one week and two months after surgery) or financial implications to healthcare providers. There is currently no evidence to support or condemn subcutaneous closure after non-childbirth surgery. Further well-designed trials are necessary.
This review is up-to-date as of 5 November 2019. The review includes four studies involving 342 adults who had received radiotherapy for the treatment of head and neck cancer. The review looks at three different ways to prevent ORN: - the use of platelet-rich plasma (PRP) in bone after removal of healthy teeth prior to radiotherapy. Plasma is a part of blood that contains special proteins that help the blood to clot, and PRP is concentrated plasma which supports cell growth. Injecting PRP into damaged tissue may stimulate the body to grow new, healthy cells to make it heal more quickly; - taking out teeth because of tooth decay makes the risk of developing ORN greater. Preventing tooth decay in people having radiotherapy is very important. We looked at a study comparing using fluoride gel with a toothpaste with a higher level of fluoride than normal to prevent tooth decay after radiotherapy; - hyperbaric oxygen therapy is breathing oxygen in a pressurized chamber to improve blood supply, which may help heal damaged tissue. Two studies compared the use of hyperbaric oxygen therapy for taking out teeth or placing dental implants with antibiotics. Antibiotics are drugs which stop or slow the growth of bacteria. One study showed no reduction in ORN when using platelet-rich plasma in bone after the removal of healthy teeth. Another study found no difference between fluoride gel and toothpaste with a higher level of fluoride than normal as no cases of ORN were reported. A third study showed that treatment with hyperbaric oxygen therapy caused a reduction in the development of ORN in comparison to patients treated with antibiotics following the removal of teeth. The fourth study found no difference between combined hyperbaric oxygen therapy and antibiotics compared to antibiotics alone. Harmful effects of the different interventions were not reported clearly or were not important. The level of certainty we have in these findings is very low. This was due to high risk of bias, not all studies mentioning important details, and the small number of people studied in the four included trials. We do not have enough evidence to say which intervention works better to stop ORN of the jaws from happening or making it less severe in adults receiving head and neck radiotherapy. We suggest that more, well-conducted, and bigger studies including more people, should be done in this area.
This review examines randomised controlled trials which compare aspects of ayurvedic medicine with the use of antipsychotics for people with schizophrenia. All trials took place in India and were for 12 weeks or less. When the ayurvedic herbs brahmyadiyoga and tagara were compared to placebo (2 trials) there was no significant difference between the two groups in acceptability of treatment or overall improvement.  The brahmyadiyoga group did, however, show some improvement when assessed ayurvedically (a combination of assessing aspects of the mind, decision, orientation, memory and habit, and looking for the absence of symptoms of illness). When these two herbs were compared to groups of people taking the antipsychotic, chlorpromazine, again there was no difference in acceptability of treatment, but in one of the two trials there was an improvement in mental state in those taking chlorpromazine. There was also a trial comparing an ayurvedic package (of herbs and other treatment) to chlorpromazine, and although both treatments were acceptable, the rest of the data were not able to be used.  Brahmyadiyoga and tagara tended to have vomiting and nausea as an adverse effect, while chlorpromazine caused people to be sleepy. It may be possible that ayurvedic treatments could be used as adjuncts to antipsychotic medication. A new larger trial comparing ayurvedic herb(s) alone, chlorpromazine alone and both together would answer this question. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).
This review included six RCTs with a total of 1501 participants that compared cerebrolysin with placebo (inactive medication) added to standard treatment of acute stroke, including thrombolysis. Three of them were large multicentre studies, two were small in size and were judged to be of unclear quality, and one did not include numerical results. The evidence is current up to June 2016. This review of six trials involving 1501 participants showed no beneficial effect of cerebrolysin in terms of death in people with acute ischaemic stroke. There was no difference in the total number of people with adverse events but a concern that cerebrolysin may increase the risk of people having non-fatal serious adverse events compared with placebo. The medication and methodology of the majority of included trials were provided by the manufacturer of cerebrolysin creating a likely conflict of interest. There is moderate-quality evidence currently available that suggests cerebrolysin performs no better than placebo in terms of all-cause death when given to people with acute ischaemic stroke within 48 hours of stroke onset. There is moderate-quality evidence that raises concerns about the increase of serious adverse events with cerebrolysin use in people with acute ischaemic stroke. Further research is likely to have an important impact on our confidence in the estimate of cerebrolysin risks in contributing to serious adverse events in people with acute stroke.
The evidence is current to October 2013. We included 19 randomized controlled trials (1940 participants) in this updated review. (We reran the search in February 2015 and found four studies of interest. We will deal with those studies when we next update the review.) Lidocaine was either put into the cuff (the cuff makes sure that the tube stays in place), sprayed onto the person's vocal cords, or used as a gel smeared on the end of the tube. The summarized results of the included studies showed positive results. However, the interpretation of the results should be judged carefully. Though the possible adverse effects of using lidocaine were not reported in the included studies, there are a few case reports about lidocaine toxicity, although this is very rare. For lidocaine therapy versus control, the quality of the evidence for risk of sore throat was low (according to Grading of Recommendations Assessment, Development and Evaluation (GRADE)). This is because most of the trials did not describe how allocation was concealed and the results of the risk of sore throat were inconsistent, the quality of the evidence of the severity of sore throat , measured by the visual-analogue scale, was moderate (according to GRADE).
This is an updated version of the original Cochrane review published in Issue 4, 2010 (Kirthi 2010); no new studies were found. A single oral dose of 1000 mg of aspirin reduced pain from moderate or severe to none by two hours in approximately 1 in 4 people (24%) taking aspirin, compared with about 1 in 10 (11%) taking placebo. Pain was reduced from moderate or severe to no worse than mild pain by two hours in roughly 1 in 2 people (52%) taking aspirin compared with approximately 1 in 3 (32%) taking placebo. Of those who experienced effective headache relief at two hours, more had that relief sustained over 24 hours with aspirin than with placebo. Addition of 10 mg of the antiemetic metoclopramide substantially increased relief of nausea and vomiting compared with aspirin alone, but made little difference to pain. Oral sumatriptan 100 mg was better than aspirin plus metoclopramide for pain-free response at two hours, but otherwise there were no major differences between aspirin with or without metoclopramide and sumatriptan 50 mg or 100 mg. Adverse events with short-term use were mostly mild and transient, occurring slightly more often with aspirin than placebo, and more often with sumatriptan 100 mg than with aspirin.
Chronic obstructive pulmonary disease (COPD) is a condition associated with high morbidity, mortality and cost to the community. Patients often report symptomatic improvement with long acting beta-2 agonists (LABAs) and anticholinergic bronchodilator medications (ipratropium). These medications have different mechanisms of action and therefore theoretically could have an additive effect when combined. As these medications are prescribed in COPD as long term therapy, it is important to know what benefit there are, if any, of prescribing ipratropium alone or as combination therapy over LABAs. Seven studies (2652 participants) were included. Salmeterol was more effective than ipratropium on lung function, but there were no major differences seen between the responses to ipratropium and salmeterol on symptoms. When we compared the combination of these two drugs with salmeterol, combination was superior to salmeterol in terms of quality of life, but the differences between these two treatments on other measurements were small and inconsistent. The findings of the review would not support a general recommendation for the use of ipratropium bromide over a beta-2 agonist alone in COPD, but the combination does confer greater benefit in health status. At this stage, people with COPD should use the bronchodilator that gives them the most improvement in their symptoms. Combination therapy should be considered, but the relative effects of this therapy in relation to other forms of inhaled therapy such as inhaled steroids and tiotropium are unknown. Cost considerations also need to be taken into account as there are considerable variations in price of bronchodilators.
Ten very different trials involving 874 adults with generally unstable fractures were grouped into six comparisons. No trial used a best-practice method for preventing selection bias. Four trials (239 participants) found implantation of bone scaffolding (autogenous - from the patient - bone graft (one trial); Norian SRS - a bone substitute (two trials); methylmethacrylate cement (one trial)) improved anatomical outcomes compared with plaster cast alone; and two found it improved function. Reported complications of bone scaffolding were transient discomfort resulting from deposits of Norian SRS outside the bone. One deposit required surgical removal. One trial (323 participants) comparing Norian SRS versus plaster cast or external fixation found no difference in functional or anatomical outcomes at one year. External deposits of bone cement and pin track infection were the only significant differences between the two groups. One trial (48 participants) found that autogenous (from the patient) bone graft in the context of external fixation did not significantly change outcome. There was one serious donor-site complication. One trial (21 participants) found some indication of worse outcomes with bone cement compared with percutaneous (through the skin) pinning. Three trials (180 participants) found bone scaffolding (autogenous bone graft (one trial); Norian SRS (one trial); methylmethacrylate cement (one trial)) gave no significant difference in functional outcomes but some indication of better anatomical outcomes compared with external fixation. Most reported complications were associated with external fixation; deposits of Norian SRS outside the bone occurred in one trial. One trial (93 participants treated with plate fixation) comparing allogenic bone material (from other people) versus autogenic bone-graft found slightly improved wrist function for the autograft group but an excess of complications relating to graft harvesting. The review concluded that while bone scaffolding may improve anatomical outcome compared with plaster cast immobilisation alone, there is insufficient evidence to conclude on function and safety; or on outcome for other comparisons.
We searched several databases (the Cochrane Library, Embase, MEDLINE, PsycINFO, and Web of Science) to find studies that assessed the impact of restricting access to means of suicide by jumping. We searched the databases up until May 2019. We included studies that assessed jumping means restriction interventions delivered on their own, such as physical barriers, fencing or safety nets on bridges, or those delivered in combination with other suicide prevention interventions, such as crisis telephones and CCTV cameras. We also searched the reference lists of all included studies and relevant systematic reviews to identify additional studies and contacted authors to obtain missing information. Our main outcomes of interest were suicide, attempted suicide or self-harm and cost-effectiveness of interventions. We found 14 relevant studies. Three studies each were from Switzerland and the USA, while two studies each were from the UK, Canada, New Zealand, and Australia respectively. The majority of studies had a before-and-after study design. Due to the observational nature of our included studies, none compared other interventions or control conditions. Jumping means restriction interventions delivered in isolation or in combination with other interventions were found to reduce the number of suicides by jumping. Data on suicide attempts were limited and no study reported self-harm. A cost-effectiveness analysis suggested that the construction of a physical barrier on a bridge would be cost-effective in the long term. The evidence for these assessments was of low quality because of weaknesses in study design and differences in findings between studies, therefore requiring the need for further high-quality studies.
The review authors searched scientific databases and Internet resources to identify randomised controlled trials (in which participants were allocated at random to any anticonvulsant drug or placebo or another type of drug or non-pharmacological intervention intended to reduce,the use of cocaine). We assessed also dropout from treatment and frequency of side effects .We included people of any gender, age or ethnicity. The review authors identified 20 studies with 2068 participants, 77% male, with a mean age of 36 years. The mean duration of the trials was 11.8 weeks (range eight to 24 weeks). All but two of the trials were conducted in the USA, all with outpatients. The anticonvulsant drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. No significant differences were found between placebo and any anticonvulsant in reducing the number of dropouts from treatment, use of cocaine, craving and severity of dependence, depression or anxiety. Side effects were slightly more frequent in the anticonvulsant groups. No current evidence supports the clinical use of anticonvulsant medications for the treatment of cocaine dependence. The quality of the evidence was moderate for the outcomes dropout and use of cocaine, and was low for the outcomes side effects and craving. The major limitation of the trials was incomplete reporting of the methods used to protect against selection bias, randomly allocate participants to groups and conceal allocation. The evidence is current to June 2014.
The review authors searched the medical literature for randomised controlled studies in which people with sickle cell disease or thalassaemia received either zinc supplements or no supplements. We included nine trials in the review (459 participants). In people with thalassaemia, there is no evidence to indicate any benefit of zinc supplements on serum zinc level. However, there was an improvement in height in those who received the supplements. There is mixed evidence on the benefit of using zinc supplements in people with sickle cell disease. For instance, there is evidence that when supplements are given for one year the serum zinc levels increased; however, haemoglobin levels and body mass index did not differ significantly between groups. We also found that people with sickle cell disease who received zinc supplements (at both three months and at one year) had fewer sickle cell crises and infections. However, given that the total number of trials is small, these results should be treated with caution.
There were few studies found (searches conducted on 30th April 2013) with few antiepileptic drugs compared. One of the four studies included showed evidence that the antiepileptic drug, sulthiame, may have a positive effect in reducing seizure frequency in BECTS in the short term. There were no significant differences in the number of patients with adverse events apart from a higher risk of rash when carbamazepine was compared to topiramate. The number of patients who discontinued treatment as a result of adverse events was also not significant in the studies reviewed. There is insufficient evidence about whether or not treating with antiepileptic drugs has any effect on seizure freedom in the longer term or on a child’s cognition. The optimum treatment has yet to be identified. More research is needed to look into the effectiveness of treatment versus no treatment on seizure control and intellect, and compare the existing treatments.
This review identified one randomised controlled study (involving 883 women) at 26 to 42 weeks' gestation and in early labour who were admitted to a tertiary hospital in USA (between July 1992 and January 1993). Measuring the amount of amniotic fluid when women were admitted did not improve infant outcomes but increased/doubled the caesarean section rate for fetal distress. The use of artificial oxytocin for augmentation of labour was also higher in the group of women who received the test than for those that did not. Because of the limited evidence (one study with a small sample size), we cannot make a meaningful conclusion or recommendations. More studies are needed.
We included 10 randomised clinical trials (RCTs), with a total of 1611 participants, that assessed seven medications (epidural and spinal morphine, spinal fentanyl, oral caffeine, rectal indomethacin, intravenous cosyntropin, intravenous aminophylline and intravenous dexamethasone). Epidural morphine and intravenous cosyntropin proved to be effective at reducing the number of participants affected by PDPH of any severity after lumbar puncture compared to placebo. Aminophylline also reduced the number of participants affected by PDPH of any severity after a lumbar puncture compared to no intervention. Dexamethasone increased the risk of PDPH when compared to placebo after spinal anaesthesia for caesarean section. Morphine also increased the number of participants affected by adverse events such as itching, nausea and vomiting. The other interventions (fentanyl, caffeine, indomethacin and dexamethasone) did not show conclusive evidence of effectiveness. Combining data was possible only for subgroups of one study comparing different dosages of caffeine to placebo, because the other RCTs appraised diverse drugs, outcomes or populations. A meta-analysis (combining of data) was not possible because all the included RCTs assessed different drugs, different doses, different outcomes or different baseline participants' characteristics. These conclusions should be interpreted carefully, given the lack of information to evaluate the risk of bias properly, and the small number of participants in the included studies.
Previous studies have shown that often patients prefer PCA to traditional methods of pain management, such as a nurse administering an analgesic upon a patient's request. This review demonstrated moderate to low quality evidence that PCA provided slightly better pain control and increased patient satisfaction when compared with non-patient controlled methods. Patients tended to use slightly higher doses of medication with PCA and suffered a higher occurrence of itching, but otherwise side effects were similar between groups.
We searched scientific databases for trials that had considered the effectiveness of the surgical treatments of urinary incontinence after prostate surgery in men. The trials had to compare surgical treatment versus no treatment, non-surgical treatment, or another surgical treatment. The evidence is current to April 2014. There are five main types of surgery and, despite some of them being in use since the 1990s, we found only one trial that met the inclusion criteria. There was very low quality evidence that the implantation of an artificial urinary sphincter (a manufactured device to prevent urine leaking out) might be more effective than injectable treatment, but with more adverse effects and higher costs. There was no evidence about the other types of surgery.
Review authors identified three randomised studies comparing different diets in 192 children and adults with different types of cancer. Other interventions, such as antimicrobial prophylaxis (i.e. prevention of infection via antimicrobial therapy such as antibiotics) and hygiene practices, and definitions of study outcomes also differed between studies, and very limited information on anticancer treatment was given. All studies had methodological problems. Unfortunately, combining the results of included studies was not possible, but at the moment, no evidence from individual studies suggests that a low bacterial diet prevents infection. Data on survival, time from onset of neutropenia to start of fever, duration of empirical (i.e. start of treatment before determination of a definitive diagnosis) antibiotics and antimycotics (i.e. agents that target fungal infection), diet acceptability and quality of life all were evaluated by only one study; for all outcomes, no statistically significant differences between treatment groups were observed. None of the studies evaluated infection-related mortality. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. No differences between diets were identified, possibly because few patients were included in these studies. On the basis of currently available evidence, the review authors were not able to give recommendations for clinical practice. Additional high-quality research is needed.
We searched for studies that compared biofeedback to either no treatment, sham treatment, or to other active treatments for IBS. We reviewed eight trials that included 300 total participants and assessed the effect of biofeedback on IBS. Each of these studies only included adults, and was carried out in an outpatient setting. The studies ranged from eight weeks to six months in length. The types of biofeedback devices varied, and included heart rate variability, measures of skin temperature or electrical resistance, and the tension of the muscles of the anus. None of the included trials disclosed funding sources. Our primary clinical outcomes were global clinical improvement and quality of life. Regarding overall improvement, three trials compared biofeedback to no treatment and found that biofeedback as part of a relaxation training program led to better symptom control than no treatment (very low-certainty evidence). Two of these trials also compared biofeedback to an attention control and found minimal symptom improvement, but the effects of chance could not be ruled out because the evidence was of very low-certainty. One trial found a greater symptom benefit with heart rate biofeedback compared to hypnotherapy (low-certainty evidence). Of two trials comparing biofeedback to counseling, any apparent effect was minimal and the effect of chance could not be ruled out (very low-certainty evidence). When rectosigmoidal biofeedback was compared to relaxation control, the effect favored the relaxation control. The addition of biofeedback to standard medical therapy was superior to medical therapy alone and to medical therapy plus sham biofeedback (low-certainty evidence for both findings). A single trial looked specifically at overall quality of life. Quality of life improved both for those in the biofeedback group and those in the cognitive therapy group, but there was no overall difference between groups. Only one trial explicitly reported on adverse events. It reported no adverse events in either the biofeedback group or the cognitive therapy group. We used the GRADE criteria to assess the certainty of the evidence for each of these findings. These ranged from low to very low. The evidence is current up to July 2019. We conclude that the existing data on biofeedback for IBS are limited and leave us uncertain about its value in IBS symptom management. The studies currently available all have design limitations that make the results difficult to apply to clinical settings. We do, however, recommend further study in this area, as biofeedback could represent a unique approach for a difficult to manage condition.
The purpose of the review was to see whether TENS is effective in relieving pain in labour. The review includes results from 17 studies with a total of 1466 women. Thirteen studies examined TENS applied to the back, two to acupuncture points and two to the cranium (head). Results show that pain scores were similar in women using TENS and in control groups. There was some evidence that women using TENS were less likely to rate their pain as severe but results were not consistent. Many women said they would be willing to use TENS again in a future labour. TENS did not seem have an effect on the length of labour, interventions in labour, or the well-being of mothers and babies. It is not known whether TENS would help women to manage pain at home in early labour. Although it is not clear that it reduces pain, women should have the choice of using TENS in labour if they think it will be helpful.
The researchers identified five studies that included a total of 329 patients. Three studies (270 patients) compared low molecular weight heparin to placebo (e.g. a sugar pill), one study (34 patients) compared low molecular weight heparin in addition to standard therapy, and one study (25 patients) compared unfractionated heparin to steroids. The study comparing unfractionated heparin to steroids and the study that compared the addition of low molecular weight heparin to standard therapy to standard therapy alone was judged to be of low quality. The three placebo-controlled studies were judged to be of high quality. In one small study, unfractionated heparin was worse than steroids for inducing clinical improvement (i.e. reduction of symptoms) in people with severe ulcerative colitis. In addition, rectal bleeding was more frequent among people who received unfractionated heparin. In another small study low molecular weight heparin used with standard therapy provided no additional benefit over standard therapy alone in adults with active ulcerative colitis. Low molecular weight heparin administered by injection showed no benefit over placebo for any outcome, including clinical remission (very low quality of evidence), clinical improvement and endoscopic improvement (i.e. healing of inflammation). High dose low molecular weight heparin administered via an extended colon-release tablet demonstrated benefit over placebo for clinical remission, clinical improvement. and endoscopic improvement. This result suggests that high dose low molecular weight heparin administered by extended-release capsules may be effective for the treatment of active ulcerative colitis. However, this result needs to be verified by future clinical trials.
We found 27 randomised controlled trials comparing these treatments with each other in a total of 4349 couples with unexplained infertility. The evidence is current to September 2018. Evidence of differences in live birth between expectant management and the other four treatments (OS, IUI, OS-IUI, and IVF/ICSI) was insufficient. If the chance of live birth following expectant management is assumed to be 17%, the chance following OS, IUI, OS-IUI, and IVF would be 9% to 28%, 11% to 33%, 15% to 37%, and 14% to 47%, respectively. Compared to expectant management/IUI, OS may increase the chances of multiple pregnancy, and OS-IUI probably increases the chances of multiple pregnancy. Evidence showing differences between IVF/ICSI and expectant management for multiple pregnancy was insufficient. If the chance of multiple pregnancy following expectant management/IUI is assumed to be 1%, the chance following OS, OS-IUI, and IVF/ICSI would be 1% to 5%, 1% to 5%, and 0% to 6%, respectively. The certainty of evidence overall was low to moderate. The main limitations were imprecision (not enough couples have been studied) and heterogeneity (couples in existing studies had different clinical characteristics).
In this review, treatment with interferon alfa in the acute stage of transfusion-acquired hepatitis C infection improved liver biochemistry and enhanced viral clearance compared to the natural history of the disease. We cannot ascertain, however, the effect of interferon on clinical outcomes due to a lack of data. Because of the effect of therapy on biochemical and virologic outcomes, we recommend the treatment of acute hepatitis C with at least interferon alfa at a dosage of three million units thrice weekly for three months. Future trials should focus on the efficacy of combination therapy with ribavirin and pegylated interferons, which have shown superiority to interferon alfa in chronic hepatitis C.
We searched for randomised controlled trials (a type of experiment in which people are randomly allocated to one or more treatment groups) up until November 2017. The search identified 23 studies involving a total of 11,170 caregivers and their children. The ages of the children ranged from birth to 24 months. The caregivers received educational interventions alone while the control group received no intervention, usual care or any other non-educational intervention. The educational methods included printed materials such as leaflets, counselling, teaching sessions, peer support, videos and practical demonstrations. Generally, the education messages were focused on the introduction of semi-solid foods at the appropriate age, the types and amount of complementary foods to be fed to infants, and hygiene. Education reduced the number of caregivers that introduced semi-solid foods to their infants before six months of age by up to 12% (moderate-quality evidence). Hygiene practices of caregivers who received education also showed some improvement compared to those that did not (moderate-quality evidence). In studies conducted in the community, education increased the duration of exclusive breastfeeding, but not in studies conducted in health facilities. There was no convincing evidence of an effect of education on the growth of children (low to very low-quality evidence). We could not combine the results from different studies for diarrhoea, knowledge of caregivers and adequacy of complementary food. However, from the individual reports of the study authors, education led to a reduction in diarrhoea and an improvement in the knowledge of caregivers. It also led to improvement in the quality and quantity of complementary foods fed to infants. Overall, we found evidence that education improves complementary feeding practices.
We searched important medical databases such as the Cochrane Central Register of Controlled Trials and MEDLINE. Two review authors independently screened, summarised and analysed the results. This led to the inclusion of seven randomised controlled trials involving with 2564 patients. The evidence provided is current to December 2016. For the comparison of chemotherapy alone and chemotherapy plus radiotherapy with the same number of chemotherapy cycles in both arms, this systematic review found no evidence for a difference regarding OS between the interventions, however, two included trials had potential other high risk of bias due to a high number of patients not receiving radiotherapy as planned beforehand. After excluding these trials in a further analysis, OS was superior in adults receiving chemotherapy plus radiotherapy than in those receiving chemotherapy alone. PFS was also superior in adults receiving chemotherapy plus radiotherapy. Most trials reported adverse events (AEs), but in different ways. Because of insufficient comparable data we focused on adverse events considered of particular interest. For infection- related mortality, second cancer- related mortality and cardiac disease- related mortality, there was no evidence for a difference between treatment groups. For complete response rate (CRR) there was no evidence for a difference between treatment groups either. For the comparison of chemotherapy alone and chemotherapy plus radiotherapy with different numbers of chemotherapy cycles in the arms, OS was reported in one trial only. The use of chemotherapy alone may improve OS compared to chemotherapy plus radiotherapy. There was no evidence for a difference between treatment groups regarding PFS. After excluding one trial with patients not receiving the planned therapy the results showed that chemotherapy plus radiotherapy improved PFS. For infection- related mortality, second cancer- related mortality and cardiac disease- related mortality, there is no evidence for a difference between treatment groups. CR was not reported. For the same number of chemotherapy cycles in both arms, we judged the quality of evidence for OS and PFS as moderate, for AEs and CR as low. For different numbers of chemotherapy cycles in the arms, we considered the quality of evidence for OS, PFS and AEs to be low. This systematic review compared the effects of chemotherapy alone and chemotherapy plus radiotherapy in adults with early stage HL . For the comparison with same numbers of chemotherapy cycles in both arms we found moderate- quality evidence that PFS is superior in patients receiving chemotherapy plus radiotherapy than in those receiving chemotherapy alone. The addition of radiotherapy to chemotherapy has probably little or no difference on OS. A further analysis without the trials with potential other high risk of bias showed that chemotherapy plus radiotherapy improves OS (both analyses moderate- quality evidence). For the comparison of chemotherapy alone and chemotherapy plus radiotherapy with different numbers of chemotherapy cycles between the arms there were no implications for OS and PFS possible, because of the low quality of evidence of the results.
This review includes 54 published trials involving 11,898 participants. Data show no apparent additional benefit of altered WBRT dose schedules compared with standard dose schedules. Use of other treatments such as chemotherapy, radiosensitisers, and molecular targeted agents in conjunction with WBRT has not yet been shown to be of benefit. Radiosurgery boost with WBRT does not improve survival among selected people with multiple brain metastases. WBRT when added to radiosurgery improves local and distant brain control. However, neurocognitive outcomes are better for selected people treated with radiosurgery alone as compared with WBRT and radiosurgery. For selected individuals with metastatic non-small-cell lung cancer to brain, survival may not be better with WBRT and optimal supportive care than with optimal supportive care alone. Studies have provided evidence of moderate to high certainty. Altered higher biological WBRT dose-fractionation schemes, as reported in randomised trials, did not confer benefit for overall survival, neurological function, or symptom control compared with standard treatment (3000 cGy in 10 daily fractions, or 2000 cGy in 4 or 5 daily fractions). However, overall survival and neurological function were worse for lower biological WBRT dose-fractionation schemes than for standard dose schedules. The addition of WBRT to radiosurgery improved local and distant brain control (i.e. absence of new intracranial lesions at the site or outside of treated lesions after treatment) among selected people with brain metastases, but investigators reported worse cognitive outcomes and no differences in overall survival. Selected people with multiple brain metastases from non-small-cell lung cancer may show no difference in overall survival when optimal supportive care is given and WBRT is omitted. Use of other treatments (radiosensitisers, chemotherapy, or molecular targeted agents) in conjunction with WBRT remains experimental. Additional trials are needed to evaluate strategies to protect cognitive decline associated with WBRT. As well, future trials should examine people with brain metastases with focus on prognostic features and tumour characteristics.
We searched for relevant trials up to 8 July 2016. These studies brought together available trial data from all over the world, with 11 trials and 2343 patients. Trials were carried out between 1966 and 1998. Results showed that fewer people given PORT treatment lived for two years after the operation (53 out of every 100 patients) than those not given PORT after the operation (58 out of every 100 patients). Researchers reported no difference in effects of PORT by types of patients included in trials. Researchers did not routinely collect quality of life information during the trials, and it was unlikely that any benefit of PORT would offset the observed survival disadvantage. Radiotherapy given after successful removal of tumour at operation is not beneficial for patients with non-small cell lung cancer and should not be used as routine treatment; however, further research into new types of radiotherapy for patients at higher risk of recurrence is ongoing. These systematic reviews and meta-analyses use individual participant data, which are considered the gold standard for this type of review. We included all eligible trials, if possible, no matter what language they were published in, or whether or not they were published. This meta-analysis included 88% of all participants in eligible trials. Studies were well designed and conducted and addressed the review question, with consistent effects noted across trials. The impact of any data not included in our analyses is small.
In 2009 we identified 14 studies, enrolling 2086 patients, and found that while statins were generally safe and reduced cholesterol levels, they did not prevent death or clinical cardiac events in people treated with dialysis. This latest update analysed a total or 25 studies (8289 patients), and included the results from two new large studies. We found that statins lowered cholesterol in people treated with dialysis but did not prevent death, heart attack, or stroke. Evidence for side-effects was incomplete, and potential harms from statin therapy remain uncertain. Current study data did not address whether statin treatment should be stopped when a person starts dialysis, although the benefits associated with continued treatment are likely to be small. Limited information was available for people treated with peritoneal dialysis, suggesting that more research is needed in this setting.
We included six randomised trials with a total of 421 participants. The evidence is current to July 2016. There were two deaths and eight serious adverse events (harmful side effects) reported in the six trials, therefore, we had insufficient data to conclude whether exercise-based cardiac rehabilitation improved outcomes that matter the most to patients, such as death and serious adverse events (e.g. hospitalisation). Exercise-based rehabilitation was not found to have a clinically relevant impact on quality of life for the patient group, but may increase exercise capacity. The quality of the evidence ranged from moderate to very low for all outcomes. It was possible for people in the trials to know to which intervention group they were randomised, the reporting of the results was not complete in many trials, and for some outcomes, the results varied across trials. These considerations limit our confidence in the overall results of the review. Further randomised clinical trials that are conducted with low risks of bias and low risks of the play of chance, in a broader population of patients with AF, are needed to assess the impact of exercise-based interventions.
We found two studies including 1073 participants that compared the long-term effectiveness and side effects of tiotropium compared to ipratropium bromide. One trial was 12 weeks long and one was a year long. The people included in the studies had moderate to severe COPD (average forced expiratory volume in one second (FEV1) was 40% the predicted value). Compared to ipratropium bromide, tiotropium treatment led to improved lung function, fewer COPD exacerbations, fewer hospital admissions (including those for exacerbations of COPD) and improved quality of life. Tiotropium appears to be safer with fewer adverse events, but there was no significant difference in deaths with ipratropium bromide when compared to tiotropium. Overall the evidence was of moderate to high quality. Tiotrpium is available in two different inhalers, Respimat and Handihaler. A recent large double-blind trial of the two delivery devices found no substantial difference in mortality using 2.5 µg or 5 µg of tiotropium via Respimat in comparison to 18 µg via Handihaler. Based on this review, tiotropium has more benefits than ipratropium bromide for people with stable moderate to severe COPD. The review was current as of August 2015.
We found eight trials involving a total of 22,604 patients. We found that taking formoterol reduced the risk of having an exacerbation that was treated with oral corticosteroids, but none of the other benefits from taking formoterol were statistically significant. Guidelines suggest that long-acting beta-agonists should be given only to patients already taking an inhaled corticosteroid. We could not find enough trials conducted in children to reach a conclusion on the benefits and harms in children, so we do not recommend using the results to make recommendations on treatment of children with asthma.
This review suggests that 50 out of 100 patients will be alive at five years, when they are given chemotherapy using a platinum drug in combination with other drugs, before having surgery and/or radiotherapy. This is compared to 45 out of every 100 patients who were given surgery and/or radiotherapy without chemotherapy. This benefit of platinum-based combination chemotherapy was seen in all types of patients and encourages its use for the treatment of invasive bladder cancer. However, chemotherapy based on a single platinum drug did not help patients live longer, and is not recommended.
The evidence is current to May 2017. We included eight studies and 334 participants related to five different classes of medicines sometimes recommended for HAI prevention. These medicines included those that mimic the action of serotonin at selected sites (selective 5-hydroxytryptamine(1) receptor agonists), medicines that regulate the action of calcium (N-methyl-D-aspartate (NMDA) antagonist), medicines that promote dilation of the blood vessels (endothelin-1 antagonist), medicines that prevent a neuron (nerve cell) from 'firing' (initiating an action) and convulsions from developing (anticonvulsant medicines), as well as medicines that regulate the body´s sodium and water levels (spironolactone). All studies were undertaken in high altitude mountain areas. The participants ranged between 16 and 65 years of age. Only one study included people at a high risk of this condition due to their history of HAI. Four trials provided the intervention between one to three days prior to the ascent (50%), and three trials less than 24 hours prior (37.5%). The participants in all these studies reached a final altitude of between 3500 and 5895 metres above sea level. Only one of the eight included studies did not provide clear information about the source of funding (12.5%). Twenty-four additional studies were classified as ongoing (12), or awaiting classification (12; unable to obtain full texts). The assessment of the less commonly used pharmacological interventions suggest that there is a scarcity of evidence related to these interventions. For most of the assessed comparisons, we only found evidence from a single study. Clinical benefits and harms related to potential interventions such as sumatriptan are still unclear. The quality of the evidence was rated from low to very low. Several studies had quality shortcomings such as only having small sample sizes and therefore generating uncertain results. For most of the medicines evaluated, additional research is required to clarify their effectiveness and safety.
Our searches identified a large body of trial evidence and also a substantial body of work in progress. This revealed that telehealthcare initiatives are unlikely to be of benefit in improving quality of life for the majority of people with relatively mild asthma, but that these interventions may prove useful in preventing exacerbations and hospital admissions in people with more severe asthma. We believe it is important for more research to be done to establish the cost-effectiveness of these interventions.
Twenty-five studies met the inclusion criteria (3615 randomly assigned participants). Only 12 of these studies were randomised controlled trials with appropriate allocation concealment. Variability was noted with regard to focus and intensity of the intervention, participant characteristics and length of follow-up. Evidence suggests that early developmental interventions improve cognitive outcomes up to preschool age. Evidence also indicates that early developmental interventions improve motor outcomes during infancy; however, these effects are small. Little evidence was found of an effect on long-term cognitive or motor outcomes (up to school age). The early developmental intervention programmes described in this review had to begin within the first 12 months of life, had to focus on the parent-infant relationship and/or infant development and, although they could begin while the baby was still in hospital, had to include a component that was delivered post discharge from hospital. The early developmental intervention programmes included in this review vary by content and by frequency and focus of the intervention. This review of 25 trials supports early developmental intervention programmes provided to preterm infants post hospital discharge with the goal of improving cognitive development over the short to medium term (up to preschool age). Variability among these early developmental intervention programmes limits the conclusions that can be drawn about their effectiveness.
This review compared the benefits and harms of laparoscopic-endoscopic rendezvous versus preoperative endoscopic sphincterotomy (cutting the muscle between the bile and pancreatic ducts) procedures followed by laparoscopic cholecystectomy to remove stones from the gallbladder and bile duct. By searching scientific databases and trials registers, we found five randomised clinical trials that compared the two approaches, and involved a total of 516 participants. The majority of the participants were females and the age of both men and women ranged from 21 years to 87 years. Only one trial stated they had not received industry sponsorship or other for-profit support. None of the other trials disclosed information about funding. Three trials stated the investigators had no competing interest; the other two trials did not provide information on competing interests. The laparoscopic-endoscopic rendezvous approach could be associated with a lower rate of overall morbidity and clinical post-operative pancreatitis, and a shorter hospital stay. We found no clear differences in overall mortality between the two techniques. Total operative time was longer with the rendezvous approach. We were unable to draw firm conclusions because of the lack of data. Further research is needed to confirm whether the single-stage approach is safer and more efficacious than the two-stage approach, and to address other important issues, such as quality of life and cost analysis. The quality of the evidence was low or very low, because of small numbers of participants, high risk of bias, and inconsistent and imprecise results across trials. The evidence is current to February 2017.
Previous studies and systematic reviews suggest that a weaning protocol should be implemented in order to make daily assessments of patients who may be ready for weaning from mechanical ventilation. The ability to breathe spontaneously can be assessed with a spontaneous breathing trial using a T-tube (T-piece) or by reducing the applied airway pressure to provide low levels of pressure support (PS) (5 to 10 cm H2O). After removal of the endotracheal tube (extubation) the patients are monitored for 48 hours. If over this period ventilatory support does not need to be reintroduced, this is taken to indicate successful weaning. For this Cochrane systematic review we searched the medical literature databases until June 2012 and included nine studies with 1208 adult patients who had been on invasive mechanical ventilation for at least 24 hours. The trials compared pressure support (PS) and the use of a T-tube (622 patients randomized to PS and 586 randomized to a T-tube). There was no clear evidence to confirm that PS was superior to a T-tube with regard to the success of weaning, need for reintubation, ICU mortality, and other factors including long-term weaning unit (LWU) length of stay, pneumonia and a rapid shallow breathing index. Among patients who received PS, a greater number of patients had a successful spontaneous breathing trial and the airway tube was removed. For respiratory rate and tidal volume outcomes PS was superior to using a T-tube in two trials. Three studies reported that the weaning duration was shorter during PS, and in one study in which patients submitted to a T-tube the weaning time was shorter. Because of limitations in the design of the studies and imprecision in the effect estimates we have rated the quality of the evidence to be low. We reran the search in December 2013. We will deal with any studies of interest when we update the review.
The review of trials found that interferons administered intramuscularly or subcutaneously can lead to a moderate reduction in recurrences and disability in people who have MS with remissions. Interferon-1a administered by the oral route was not effective for prevention of relapses. Side effects were usually influenza-like symptoms, injection site-reactions, pains in the joints and muscles, fatigue and headache.
The authors found 23 studies; only five of these measured the effect on injury, the remaining 18 measured the effect on behaviour (by the patrons and/or the servers of the alcohol within the premises). The studies investigated a range of interventions involving server training, health promotion initiatives, a drink driving service, a policy intervention and interventions that targeted the server setting environment. The authors concluded that there is insufficient high quality evidence that interventions in the alcohol server setting are effective in preventing injuries. The evidence for the effectiveness of the interventions on patron alcohol consumption was found to be inconclusive. There is conflicting evidence as to whether server behaviour is improved and it is difficult to predict what effect this might have on actual injury risk. Lack of compliance with interventions seems to be a particular problem; hence mandated interventions or those with associated incentives for compliance, may be more likely to show an effect. The methodology of future evaluations needs to be improved. The focus of research should be broadened to investigate the effectiveness of interventions other than server training, where previous research dominates. When the collection of injury outcome data is not feasible, research is needed to identify the most useful proxy indicators.
For women wishing to become pregnant spontaneously, we found one trial (200 women). For women undergoing IVF, we included ten trials (3750 women). All trials evaluated the effects of screening hysteroscopy compared to no hysteroscopy. The evidence is current to September 2018. In women wishing to become pregnant spontaneously, hysteroscopy was associated with a higher chance for an ongoing and clinical pregnancy in one study at high risk of bias. The trial reported no adverse events following hysteroscopy. The miscarriage rate was higher following hysteroscopy. In women undergoing IVF, the included studies suggested that performing a screening hysteroscopy first, improved the chances of live birth or clinical pregnancy. However, adverse events following hysteroscopy were poorly reported, and therefore, we were unable to assess the safety of this intervention. For women at a typical clinic with a 22% live birth rate, performing a screening hysteroscopy would be expected to result in live birth rates between 25% and 32%. There was no increased risk of miscarriage following hysteroscopy. We found no trials with women who were seeking intrauterine insemination. There was very low-quality evidence from one study in women who were trying to become pregnant spontaneously. There was low-quality evidence that a screening hysteroscopy, performed prior to IVF, may increase the chance of live birth or clinical pregnancy, and very low-quality evidence about adverse events following hysteroscopy. The quality of the evidence was reduced because of risk of bias and statistical heterogeneity.
The Cochrane Oral Health Group carried out this review of existing studies, which includes evidence current up to 27 September 2013. This review includes one published study in which a total of 185 children and young adults were randomly chosen to have a clinical examination every 12 months or every 24 months. The study measured what effects the two different check-up times had on tooth decay and total time used per person (which could then be used to measure costs to the healthcare system). The limited results did not enable a conclusion to be made about whether or not extending the time to the next dental check-up can reduce tooth decay or costs. The evidence presented is of very low quality due to there only being one study and issues with the way it was conducted.
The umbilical cord connects the baby and mother during pregnancy. The cord is cut after birth. The cord stump then dries and falls off, generally within five to 15 days. Infection of the umbilical cord stump (omphalitis), caused by skin bacteria, is a significant cause of illness and death in newborn babies in developing countries. This review evaluated all studies that assessed antiseptics applied topically to the umbilical cord to determine if they reduce the risk of cord infection and death. Thirty-four randomised controlled studies were included involving 69,338 babies. There were 22 different interventions studied. The most commonly studied antiseptics in the included studies were 70% alcohol, triple dye and chlorhexidine. Three studies were conducted in community settings in developing countries; the remainder were conducted in hospital settings, mostly in developed countries. Studies conducted in community settings were large and contributed about 78% of all the participants included in this review. Hospital-based studies were small and had limitations. Studies conducted in community settings evaluated the effectiveness of topical application of chlorhexidine and combined results showed that chlorhexidine reduced risk of death by 23% and the risk of cord infection ranging from 27% to 56%, depending on the severity of infection. Topical application of chlorhexidine may increase cord separation time by about 1.7 days, however, this does not increase subsequent risk of cord infection or death. None of the studies conducted in hospital settings reported data for risk of death or tetanus. No antiseptic was found to be advantageous for the prevention of cord infection compared with dry cord care in hospital settings. Topical triple dye application reduced bacterial colonization with Staphylococcus aureus compared to both dry cord care and alcohol application. There was no advantage of application of alcohol and triple dye for reduction of colonization with streptococcus. Topical alcohol application was advantageous in the reduction of colonization with Enterococcus coli compared with dry cord care and triple dye application. Cord separation time was increased with topical application of alcohol and triple dye compared with dry cord care in hospital settings. There were insufficient studies to determine the efficacy of other antiseptics.
This review examines the evidence from studies comparing different types of open surgery for people with groin hernia. We included only randomised studies comparing either 1) methods using synthetic mesh versus methods without mesh or 2) flat mesh methods versus plug and mesh methods. We divided mesh methods into flat mesh, plug and mesh or preperitoneal mesh and non-mesh methods into Shouldice or other non-mesh repair. We found 20 studies comparing mesh with non-mesh repair and two studies comparing flat mesh with plug and mesh. For 13 studies we re-analysed data supplied by the study author, for four studies we received additional results from the study author and for five studies only published information was used. There was strong evidence that fewer hernias recur after mesh repair than following non-mesh repair. There was a suggestion that people had less persisting pain after mesh repair but results were only available for nine out of 20 trials. Open mesh methods were shorter to perform than Shouldice procedures, but took longer than other types of non-mesh repair. We found no clear differences between mesh and non-mesh methods for operative complications and persisting numbness. Overall, people spent less time in hospital and returned to their usual activities quicker after mesh repair but this pattern was not observed for all studies. We did not find clear evidence of differences between flat mesh repair and plug and mesh repair.
This review focused on encouraging children to wear helmets, as distinct from compelling them to do so through laws. The authors wanted to find out which sort of helmet programmes work best, particularly with children from poor families who are less likely to own helmets. They found 29 helmet promotion programmes that had been studied. The programmes varied widely with regard to where they were carried out, age of the children, programme methods, etc. The results were also very varied but overall 11 studies found that after a helmet programme children were more likely to be observed wearing helmets than other children. More research is still needed but it seems likely that the best schemes are based in the community and involve both education and providing free helmets. Promotion of helmets in schools also seems to be effective. Promoting helmets appears to be more effective for younger children (aged 12 years and under) than for older children and young people. The studies reviewed did not look at the impact of helmet programmes on injury rates, or assess whether programmes had any negative effects such as reducing cycling. Most of the studies were undertaken in higher-income countries and the additional effect of helmet promotion above existing legislation was not explored. More research is needed to understand more about whether providing subsidised helmets is as effective as providing free helmets and whether programmes in healthcare settings are as effective as those in schools or communities. Other types of helmet programmes (e.g. those including peer educators, those developing skills such as decision making and resisting peer pressure, or improving self esteem or self efficacy) need developing and testing, particularly for 11 to 18 year olds. The effect of helmet programmes in countries with existing cycle helmet legislation and in low and middle-income countries also requires investigation.
In July 2013, we did computer searches for randomized trials of pills with 20 µg estrogen versus more estrogen. We did not find any new trials. For the initial review, we also wrote to researchers and makers of birth control pills to find other trials. Studies had to be written in the English language, include at least three cycles, and focus on birth control. The trials had to report on pregnancy, bleeding problems, or stopping the pills early. We also looked at side effects. More women taking the pills with less estrogen quit the studies early. The women on less estrogen also had more bleeding problems than those taking pills with more estrogen. Pregnancy rates seemed to be the same between groups, but the studies may not have been large enough to know for sure. This review did not focus on the rare events needed to test whether birth control pills with 20 µg estrogen were safer. Also, most trials compared pills with different types of the hormone progestin, which could also affect bleeding patterns. The high losses in many trials make the results hard to interpret.
We searched scientific databases for clinical trials looking at ways of improving adherence to drug treatment in people with epilepsy. We limited our search to randomised controlled trials involving people with a clinical diagnosis of epilepsy of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting. The results are up-to-date to February 2016. We identified twelve trials (1642 participants). The trials were conducted in different countries with the majority from the United States. The trials examined three main types of interventions: i) education and counselling of participants about topics such as epilepsy and medication used to control epilepsy, ii) behavioural interventions such as asking epileptic patients to link the intention of taking their medication with a particular time, place and other routine activity and iii) the use of more than one intervention (mixed interventions). Behavioural interventions and mixed interventions resulted in an improved adherence in the intervention groups compared to the control groups. Four trials showed that when adherence improved in the intervention groups, seizure frequency or seizure severity was decreased. Many of the included trials are of moderate quality and have limitations in the design. Therefore, it is difficult to draw firm conclusions. We need carefully-designed randomised controlled trials involving more people with longer follow-up periods to identify the best intervention to improve adherence to antiepileptic medication.
We found 98 studies from 15 countries. Of the 88 core studies, 37 asked advocates about their views and experiences and seven asked abused women about advocacy (two of these also asked staff). The other 44 core studies helped us understand the way advocacy works and how effective it is. We included 10 additional studies that did not fit the original criteria but added useful information, as befitting a realist approach. Of these, three were randomised controlled trials (RCTs; a type of experiment in which participants are randomly allocated to two or more interventions), one was an intervention process evaluation, one was a qualitative (e.g. focus groups, interviews) study, two studies used mixed methods (a combination of qualitative and quantitative research) to explore women's experiences, two were surveys of women, and one was a mixed methods study of women and staff. We were unable to obtain the full texts of two studies that we thought might be core and three further relevant studies are still ongoing. Advocacy interventions varied considerably in duration, participating staff (e.g. nurses, psychologists, social workers), and setting (e.g. healthcare settings, domestic violence refuges or shelters). In the studies, women and advocates agreed that the following were all important parts of advocacy: education and information on abuse and on women's rights and sources of help (resources); active referral to, and help in accessing other services; assessment of risk of repeat abuse; and safety planning to avoid it. Trust in the advocate is important and more likely when the advocate and the woman share an ethnic background or the advocate was also abused. Advocates must help women consider their best options, depending on things like ethnicity, immigration status, where they live, the severity and type of the abuse experienced and finances. There are trade-offs when making decisions to reduce the abuse and women's safety was not necessarily at greatest risk from staying with the abuser. Advocacy could potentially have some benefits for abused women, if undertaken for long enough, but its goals need to match each woman's needs. It may take months to have an effect. Two studies (one involving the police and one in an antenatal clinic) found that where abuse is severe to start with, some interventions may possibly prompt the abuser to increase the abuse. Advocates want to help women and can get stressed if they do not feel helpful enough, so they need support from organisations and other advocates, including repeat training, debriefs, and funding to do their job well. Our confidence in the key findings varied between moderate and high. However, some themes (the effect on outcomes of women being physically dependent on their abuser, being pregnant or having children) were less well supported by evidence and further, good-quality research is needed to confirm findings. Researchers should be careful when choosing how to measure abuse so that measures have more meaning for advocates and abused women, thus increasing the usefulness of future reviews. Further evidence from studies where participants are followed up for years would be helpful. More economic analyses are needed to establish if current advocacy interventions are the best way of spending money for abused women.
We included 34 studies (1614 women) that evaluated three techniques: blue dye only, technetium (a radioactive substance) only, or blue dye and technetium combined. Ten studies used all three techniques during the course of the study (one technique per participant). There are two attributes to a test: the ability to identify or detect the sentinel node, and the ability to identify the cancer in the sentinel node. We found that all tests can identify cancer in the groin nodes with good accuracy (more than 90% of nodes with cancer will be accurately identified with any of the tests), although the combined test was the most accurate (95%). The ability of the tests to detect sentinel nodes varied, with the blue dye test only detecting sentinel nodes in 82% of women, compared with 98% for the combined test. If sentinel nodes are not detected, they cannot be examined for cancer cells; therefore, women in whom sentinel nodes are not detected will usually need to undergo IFL. The combined and technetium only tests are able to predict accurately which women have cancerous spread to the groin. For a group of 100 women undergoing assessment, the findings mean that approximately one or fewer women having the combined or technetium only tests will undergo an unnecessary IFL, compared with approximately 11 women having the blue dye only test. This is mainly because the blue dye only test is not as good as technetium in identifying sentinel nodes. Fewer women with spread to the groin will be missed with the combined or technetium only tests (1 to 3 out of 30) compared with the blue dye only test (1 to 8 out of 30). It is not clear whether women with negative sentinel nodes (i.e. no spread of cancer to the groin lymph nodes) who do not undergo IFL will live as long as those who undergo IFL. The current best data on survival come from a Dutch study that followed up 259 women with negative sentinel nodes and reported a three-year survival of 97%.
The only identified randomised clinical trial did not demonstrate any beneficial effect of D-penicillamine on the course, complications, and survival of patients with primary sclerosing cholangitis. In addition, its use was associated with a number of adverse events. Therefore, we cannot recommend the use of D-penicillamine outside randomised trials.
We searched scientific databases for clinical trials comparing different blood thinners in people with cancer with a confirmed diagnosis of deep vein thrombosis (a blood clot in the limbs) or pulmonary thrombosis (a blood clot in the lungs). We included trials of adults and children with either solid tumors or blood cancer irrespective of the type of cancer treatment. The trials looked at death, recurrent blood clots, and bleeding. The evidence is current to January 2018. We included 15 trials. In this systematic review, data from five studies with 422 participants suggested that the effect of low molecular weight heparin on death compared with unfractionated heparin was uncertain, but if anything of small size. There was not enough evidence to prove superiority in reducing recurrence of blood clots or risk of bleeding. We found no data to compare the safety profile of these two medications. Also, fondaparinux did not prove or exclude any important effect compared to heparins, on death, blood clots, or bleeding. Similarly,the available evidence did not show any difference between dalteparin and tinzaparin for all tested outcomes. We judged the certainty of evidence for low molecular weight heparin versus unfractionated heparin to be moderate for all assessed outcomes. We judged the certainty of evidence for fondaparinux versus heparin to be moderate for all tested outcomes. We judged the certainty of evidence for tinzaparin versus dalteparin to be low for all tested outcomes.
We included studies of adults who received planned surgery with general anaesthesia. We looked at seven psychological preparation techniques: procedural information (information about what, when and how processes will happen); sensory information (what the experience will feel like and what other sensations they may have, e.g. taste, smell); behavioural instruction (telling patients what they need to do); cognitive intervention (techniques that aim to change how people think); relaxation techniques; hypnosis; and emotion-focused interventions (techniques that aim to help people to manage their feelings). The psychological preparation had to be delivered before surgery for the study to be included in the review. We included studies that looked at the effect of psychological preparation on pain, behavioural recovery, length of stay and negative emotion after surgery (within one month). Studies were included in the review up to the search date of 4 May 2014. We updated the search on 7 July 2015 and will incorporate the 38 studies found in this later search when the review is updated. We included 105 studies from 115 papers, with 10,302 participants taking part. Sixty-one studies measured the outcome pain, 14 behavioural recovery, 58 length of stay and 49 negative emotion. In accordance with the review protocol, we did not record details about funding sources. In this review we included 105 studies, which were reported in 115 papers. A total of 10,302 participants were randomized in these studies. For pain, length of stay and negative emotion we combined numerical findings from the studies. We found that psychological preparation before surgery seemed to reduce pain and negative emotion after the operation and may reduce the time spent in hospital by around half a day but the quality of the evidence was low. Also, the studies used many different psychological preparation techniques (often in different combinations) so it was not possible to discover which techniques were better. We could not statistically combine numerical findings for behavioural recovery because few studies provided sufficient details and studies used different ways of measuring how quickly people returned to usual activities. In reviewing the studies, we found that psychological preparation, in particular behavioural instruction, may have the potential to improve behavioural recovery. However, the quality of this evidence was very low. We looked at the effect of psychological preparation on pain, behavioural recovery, length of stay and negative emotion in this review and did not find evidence to suggest that psychological preparation might lead to harm in these outcomes. However, as we did not look at other outcomes it is possible that we did not identify potential harm. Many studies were poorly reported, so we could not be confident that findings were reliable. For this reason and because of the large variation in psychological techniques, types of surgery and measures used, we graded the quality of the evidence as `low' for the outcomes pain, negative emotion and length of stay; we cannot be confident that these techniques help patients to recover from surgery. For behavioural recovery, we further downgraded the quality of the evidence to `very low' because of problems with measurement and reporting of the outcome.
Randomised trials comparing bone marrow-derived cells with no cells in patients diagnosed with acute myocardial infarction were eligible for this review. We searched databases to March 2015. This review was supported by the National Institute of Health Research (NIHR) through its Cochrane Incentive Award programme. In this updated systematic review we analysed data from a total of 41 trials with over 2700 patients. Evaluation of the currently available evidence indicates that this treatment may not lead to improvement when compared to standard treatment, as measured by the frequency of deaths, heart attacks and/or heart failure requiring re-hospitalisation following treatment, as well as tests of heart function, in the short and long term. The evidence in this review is of moderate quality due to the small number of events.
We searched for studies up to September 2018, and we found 10 studies, including 3655 people. All of these people were smokers, over 18 years of age. Studies tested different ways of helping people use their stop-smoking medicines properly. Typically this meant providing additional information about the medicine or helping people to overcome problems they had with taking the medicine. One study delivered support by telephone, and the rest provided at least some face-to-face support. All included studies measured the amount that people used their medicines and all but one measured how many people quit smoking. People who received help to improve their use of medicines to stop smoking used their medicines slightly more than people who did not receive this help. There was some evidence that this also led to slightly more people quitting smoking. The evidence that helping people improve their use of stop-smoking medicines can successfully boost the use of these medicines is of moderate quality, meaning that more evidence could make us feel more certain of this effect. This is because there were problems with the methods of some of the included studies. The evidence suggesting that approaches to improve the use of stop-smoking medicines can help more people to quit smoking is of low quality, which means that we are not confident that they do actually help more people to quit and further evidence may or may not strengthen our confidence in this effect. This is because there were problems with some of the study methods and because it is unclear whether providing extra support to encourage people to use their medicines leads to more or fewer people successfully quitting smoking.
We included studies that assessed the effects of centre-based day care for children younger than five years of age in low- and middle-countries. To isolate the effects of day care, we excluded interventions that involved medical, psychological or non–child-focused co-interventions. Of the 34,902 citations identified through electronic searches, we found only one study that met our inclusion criteria. This study was based in Kenya, Uganda and Tanzania/Zanzibar and included 256 children. Evidence is current to April 2014. The one included study reported positive effects of centre-based day care on the cognitive development of children. It did not report the effects of centre-based day care on children's psychosocial development, the incidence or prevalence of infectious diseases, parental employment or household income. This review includes only one trial. This study did not assign participants to the intervention by chance, so the comparison groups may have differed in important ways. Therefore results must be interpreted with caution. Although current studies do not now allow for conclusive judgements regarding the effects of centre-based day care on the development of children and the economic situation of parents, this does not imply that these services are not important in low- and middle-income countries. Effectiveness studies of centre-based day care without co-interventions are few, and the need for such studies is significant. This review is one of a pair of reviews; researchers and practitioners may find evidence from the high-income country review to be informative also (Van Urk 2014).
We included nine randomised controlled trials (RCTs), none supported by industry, with 3665 participants directly comparing bevacizumab with ranibizumab. Six RCTs were completed and published, two RCTs were completed, but unpublished, and one was still in progress. We were able to include safety information from all trials, accessing both published and unpublished data. Drugs were administered for up to two years according to continuous or discontinuous treatment. In the first, drugs were regularly administered, irrespective of the remission or progression of the disease; the latter involved 'as needed' (pro re nata, PRN) or 'treat-and-extend' regimens in which the drug was injected less frequently as long as there was no recurrence of neovascular manifestations. Follow-up for adverse events occurred at regular intervals up to one or two years, irrespective of continuous or discontinuous treatment. All studies used the approved dosage of ranibizumab (0.5 mg) according to the 'Summary of Product Characteristics', and the dosage of bevacizumab most recommended by ophthalmologists for intravitreal injection (1.25 mg). Three studies excluded patients at high cardiovascular risk. However, four RCTs considered patients at different cardiovascular risks, representing a wide spectrum of risks and routine practice in hospital settings. Our review found the systemic safety of bevacizumab for neovascular AMD to be similar to that of ranibizumab, except for gastrointestinal disorders, which was a part of a secondary analysis. If 1000 people were treated with ranibizumab for one or two years, 34 would die. If treated instead with bevacizumab, between 27 and 53 of them would die. If 1000 people were treated with ranibizumab, 222 would experience one or more SSAEs. If 1000 people were treated instead with bevacizumab, between 200 and 291 would experience such an event. Deaths are likely to be unrelated to the administration of drugs. We could not fully assess the quality of three unpublished studies. We rated the overall quality of the evidence as low to moderate because we could not be certain that one drug was better than the other one on many of our outcomes. Another limitation of the studies was the participants who were recruited into them, and the fact that studies may have missed measuring the outcomes of interest in a few individuals that might have experienced a SSAE. Missing information was equally common in participants treated with bevacizumab and those treated with ranibizumab.
Compared with placebo, these medicines provide a small improvement in lung function measurements and reduce the likelihood of an exacerbation of COPD. Based on these results, we would expect that out of 100 people who took PDE4 inhibitors every day for a year, 28 would experience at least one exacerbation which is five fewer than for others who did not receive these medicines. However, people reported that these medicines only provided a small effect on levels of breathlessness and quality of life. Furthermore, around 5% to 10% of people in trials who received roflumilast or cilomilast reported side effects such as diarrhoea, nausea and vomiting. We would expect that out of 100 people who took PDE4 inhibitors every day for a year, 11 would experience diarrhoea, which is seven more than for others who did not receive these medicines. There was also a two- to three-fold increase in the risk of sleep or mood disturbance for the roflumilast 500 μg dose, although overall the total number of reported incidents was still small. There was no effect on rates of hospitalisation and deaths. The effects were the same regardless of the severity of COPD, or whether other medicines for COPD were being taken. The studies were generally well designed, as people did not know if they were receiving this new treatment or a placebo medicine. Overall we rated the evidence as being of moderate to high quality. It is of concern that results seen in trials published in journals by pharmaceutical companies showed a greater benefit of these medicines than those which were unpublished. Therefore, this relies on unpublished trial data being made accessible and up to date. The psychiatric adverse effects data remain unpublished. Longer-term trials are necessary to get a more accurate estimate of the benefits and safety of these medicines over time, including whether they slow COPD disease progression.
We included 17 studies that involved a total of 9975 adult participants and lasted between 1 and 92 weeks. We only compared ranolazine and placebo because there were few data for other comparisons. The evidence was uncertain about the effect of ranolazine 1000 mg given alone twice daily to people with stable angina pectoris on the chance of dying from heart-related causes. There was no evidence about whether ranolazine changed the risk of dying from causes that were not heart-related. Although the evidence was uncertain about the effect of ranolazine 1000 mg twice daily on the chance of dying from any cause, quality of life, the possibility of heart attack or the frequency of angina attacks (for ranolazine taken alone), ranolazine did modestly reduce the numbers of angina attacks per week when given with other anti-angina drugs. Ranolazine 1000 mg twice daily increased the risk for experiencing dizziness, nausea and constipation from taking the drug (mild adverse events). Overall, evidence quality was assessed as very low for the chance of mild adverse events (for people who took ranolazine alone). Evidence was also low for estimating the chance of death from heart-related (when ranolazine is taken alone) or any causes, having a heart attack, and how often angina attacks occur (when ranolazine is taken alone). We found moderate quality evidence about quality of life, frequency of angina attacks and the chance of experiencing mild adverse events (for people who took ranolazine together with other anti-angina drugs), Low evidence quality related to problems and reporting of study methods and too few data to calculate precise estimates.
We included five randomised controlled trials of women with PCOS undergoing gonadotrophin treatment for ovulation induction. This review of trials compared metformin or placebo added to gonadotrophins for ovulation induction. Evidence is current to July 2016. We were able to include only five trials with a total of 264 women. We graded the quality of the evidence as low. We found no evidence of a difference in risk of multiple pregnancy between metformin and placebo, but we noted higher rates of live birth, ongoing pregnancy and clinical pregnancy with metformin. Evidence was of low quality for live birth, ongoing pregnancy, clinical pregnancy and multiple pregnancy. Limitations of the evidence included inadequate reporting of study methods and blinding of participants and outcome assessors.
Other studies suggest that a low-phenylalanine diet can reduce blood phenylalanine levels. The review includes four studies, but we were not able to combine many results. Results from one study showed that blood phenylalanine levels were lower and intelligent quotient higher for people on a special diet. We recommend that a low-phenylalanine diet should be followed from the time of diagnosis. More research is needed to show if it is safe to relax this diet later on.
Some studies showed positive effects on researchers' attitudes to plagiarism. Practical training, such as using computer programs that can detect plagiarism, or writing exercises, sometimes decreased plagiarism by students but not all studies showed positive effects. We did not find any studies on fabrication or falsification. Two studies showed that the way in which journals ask authors for details about who did each part of a study can affect their responses. Many of the studies included in this review had problems such as small sample sizes or had used methods that might produce biased results. The training methods tested in the studies (which included online courses, lectures and discussion groups) were often not clearly described. Most studies tested effects over short time periods. Many studies involved university students rather than active researchers. In summary, the available evidence is of very low quality, so the effect of any intervention for preventing misconduct and promoting integrity in research and publication is uncertain. However, practical training about how to avoid plagiarism may be effective in reducing plagiarism by students, although we do not know whether it has long-term effects.
This review of five studies compares the effects of blood transfusion at low levels of haemoglobin to transfusion at high levels. Within the levels tested, there were no differences seen in survival, in the serious complications of prematurity, or in longer term development as measured at 18 to 21 months past the baby's due date. Allowing the baby to become a little more anaemic did not affect the baby's weight gain or breathing patterns. These conclusions are not firm, because too few babies have been studied. Our overall recommendation is not to exceed the higher levels of haemoglobin used in these trials, and thus diminish the risks of over-transfusion, but not to allow the level of haemoglobin to fall below the lower limits tested in these studies until further studies are completed.
This review looked at the effect of bisphosphonates on pain caused by bone metastases. Bisphosphonates do have some effect but are not as useful as either strong analgesics (such as morphine) or radiotherapy. However, where other methods of pain relief are inadequate, the addition of bisphosphonates can be beneficial. Bisphosphonates can cause nausea and vomiting.
This review aimed to test whether any anticoagulant regimen offers net advantages over antiplatelet agents, overall, or in specific categories of patients. There was no evidence that anticoagulants are superior to antiplatelet agents (in fact, anticoagulants caused a small increase in the number of deaths at long-term follow-up). However, the combination of low-dose anticoagulant and aspirin seemed to offer benefits over aspirin alone, and the combination should be investigated further.
We identified only two randomised controlled trials that compared oral aspirin (300mg daily) plus compression with compression and placebo, or compression alone. One study conducted in UK included 20 participants (ten in the aspirin group and ten in the control group) and followed people for four months. This trial reported that the ulcer area had reduced (by 6.5 cm², a 39.4% reduction) in the aspirin group compared with no reduction in ulcer area in the control group, and that a higher proportion of the ulcers (38%) in the aspirin group had completely healed compared with none in the control group. Recurrence was not investigated in this study. Another study conducted in Spain included 51 participants (23 in the aspirin group and 28 in the control group) and followed people until their ulcers had healed. The study reported that the average time for healing was 12 weeks in the aspirin group and 22 weeks in the control group, and that there was no real difference between the proportion of people with ulcers healed (17 (74%) out 23 people in the aspirin group and 21 (75%) out 28 people in the control group). The average time for recurrence was longer in the aspirin group (39 days) compared with (16.3 days) in group of compression alone. Adverse events were not reported in either trial. We considered these two studies too small and low quality for us to draw definitive conclusions about the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. The UK study provides only limited data about the potential benefits of daily oral aspirin therapy with compression due to a small sample size of only 20 participants and short follow up. The Spanish study provides limited data on 51 participants comparing aspirin and compression to a control group. The fact that no information was reported regarding placebo in the control group means the estimate of effect is uncertain. Further high quality studies are needed in this area. This plain language summary is up to date as of 27 May 2015.
The last search for trials was in August 2018. We assessed the evidence from seven clinical trials in which people received either phenobarbitone or phenytoin and their treatment was decided randomly. We were able to combine data for 635 people from five of the seven trials; for the remaining 163 people from two trials, data were not available to use in this review Key results This review found no evidence to suggest a difference between phenobarbitone and phenytoin in terms of the time to seizure recurrence and time to seizure remission (seizure free period of six or 12 months). Phenobarbitone treatment was more likely to be withdrawn than phenytoin treatment, however, this may have been influenced by the design of the included studies (whether the people and the clinicians treating them knew which treatment the person was receiving). Quality of the evidence Some of the trials contributing data to the review had methodological problems, which may have introduced bias and inconsistent results into this review. Also, we believe that the difference in study design with regards to whether the treatment was masked from the patients and clinicians (e.g. with a placebo tablet) had an impact on the rates of withdrawal from the study treatments, which also is likely to have impacted on the outcomes related to seizure control These problems may have affected the results of this review and we judged the quality of the evidence provided by this review to be moderate to low quality. We do not suggest using the results of this review alone for making a choice between phenytoin or phenobarbitone for the treatment of epilepsy. Future trials comparing these drugs or any other antiepileptic drugs should be designed using high-quality methods to ensure results are also of high quality.
In June 2017 we searched for studies evaluating the effect of the education of healthcare professionals on pressure ulcer prevention, and found five relevant studies. Two studies explored the impact of education on the prevention of pressure ulcers. We are uncertain whether education of healthcare professionals makes any difference to the number of new pressure ulcers that develop. This is because the certainty of the evidence within the studies was very low. Three studies explored the impact of education on staff knowledge of pressure ulcer prevention. The studies compared: education versus no education; components of educational intervention in a number of combinations; and education delivered in different formats. We are uncertain whether education makes any difference to staff knowledge of pressure ulcer prevention, or to the number of new pressure ulcers that develop. This is because the certainty of the evidence within the studies was very low. No study explored the impact of education on the treatment provided by health professionals. Only one study explored the secondary outcomes of interest: pressure ulcer severity, patients' views on their quality of life and carers' views on the patients' ability to carry out daily tasks independently. However, there was not enough information provided within the study to enable our independent assessment of these outcomes. We examined the certainty of the evidence using the GRADE approach and concluded that all of the evidence was of very low certainty. Therefore we are unable to determine whether education can prevent pressure ulcers. We are also unable to determine whether education affects the knowledge that healthcare staff possess about preventing pressure ulcers. The evidence of this review is up-to-date as of 12 June 2017.
Evidence from twelve small randomised trials were combined. Most trials had unclear methodologic quality. Overall, support systems did not appear to affect mortality or bridging to transplantation, but had a beneficial effect on hepatic encephalopathy. The risk of adverse events could not be established. Further evidence is needed before support systems can be recommended for routine use.
We analysed reports from seven randomised controlled trials of 1205 patients and found that ureteroscopy provided a better stone-free rate after treatment, but patients had to stay in hospital longer, and there was a higher risk of complications. We found that there were many variations among the seven studies in their design, duration, and data collected which made comparison and evaluation challenging. We recommend that further evaluation and research is conducted to ensure that new and improved treatments and studies are considered to inform clinical practice.
A LHW is a lay person who has received some training to deliver healthcare services but is not a health professional. In most of the studies in this review, LHWs offered health care to people who were on low incomes living in wealthy countries or to people living in poor countries. The LHWs in wealthy countries offered health promotion, counselling and support. The LHWs in poor countries offered similar services but they sometimes also distributed food supplements, contraceptives and other products, treated children with common childhood diseases, or managed women in uncomplicated labour. What the research says The studies described the experiences of LHWs, mothers, programme managers, and other health workers with LHW programmes. Many of our findings were based on studies from different settings and had some methodological problems. We judged these findings to have moderate certainty. Some findings were only based on one or two studies that had some methodological problems and were judged to be of low certainty. Mothers were generally positive about the programmes. They appreciated the LHWs’ skills and the similarities they saw between themselves and the LHWs. However, some mothers were concerned about confidentiality when receiving home visits. Others saw LHW services as not relevant or not sufficient, particularly when LHWs only offered promotional services. LHWs and mothers emphasised the importance of trust, respect, kindness and empathy. However, LHWs sometimes found it difficult to manage emotional relationships and boundaries with mothers. Some LHWs feared blame if health care was not successful. Others felt demotivated when their services were not appreciated. Support from health systems and community leaders could give LHWs credibility if these health systems and community leaders had authority and respect. Active support from family members was also important. Health professionals often appreciated the LHWs' contributions to reducing their workload, and their communication skills and commitment. However, some health professionals thought that LHWs added to their own workloads and feared a loss of authority. LHWs were motivated by altruism, social recognition, knowledge gain and career development. Some unsalaried LHWs wanted regular payment. Others were concerned that payment might threaten their social status or lead people to question their motives. Some salaried LHWs were dissatisfied with their pay levels. Others were frustrated when other LHWs had higher salaries. Some LHWs said that they had few opportunities to voice complaints. Some LHWs described insufficient, poor quality and irrelevant training programmes. They called for more training in counselling and communication and in topics outside their current role, including common health problems and domestic problems. LHWs and supervisors complained about supervisors’ lack of skills, time and transportation. Some LHWs appreciated the opportunity to share experiences with other LHWs. Some LHWs were traditional birth attendants who had received additional training. Some health professionals were concerned that these LHWs were over-confident about their ability to manage danger signs. LHWs and mothers identified women’s reluctance to be referred after bad experiences with health professionals, fear of caesarean sections, lack of transport, and costs. Some LHWs were also reluctant to refer women on because of poor co-operation with health professionals. We organized these findings into chains of events where we have proposed how certain LHW programme elements might lead to greater programme success. Authors’ conclusions Rather than being seen as a lesser trained health worker, LHWs represent a different and sometimes preferred type of health worker. The often close relationship between LHWs and their recipients is a strength of such programmes. However, programme planners must consider how to achieve the benefits of closeness while avoiding the problems. It may also be important to offer services that recipients perceive as relevant; to ensure regular and visible support from other health workers and community leaders; and to offer appropriate training, supervision and incentives.
We searched scientific databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) that were designed to evaluate the effectiveness and safety of ECP for the management of chronic graft-versus-host disease in children and adolescents (under 18 years of age) after HSCT. The original version of this review and this 2015 review update found no RCTs that analysed the efficacy of ECP for paediatric patients with chronic graft-versus-host disease after HSCT. Current recommendations are based on retrospective (a study in which the outcomes have occurred to the participants before the study began) or observational (a study in which the investigators do not seek to intervene, and simply observed the course of events) studies only. Thus, ideally, ECP should be applied in paediatric patients in the context of RCTs only. ECP may be considered in people with steroid-refractory chronic GvHD, keeping in mind that such a treatment is not supported by high-level evidence. If treatment decisions based on clinical data in favour of ECP are made, patients should be carefully monitored for beneficial and harmful effects and efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP.
We found three randomised controlled trials that compared EK with PKP, one of which used the FLEK method. The evidence was current to January 2014. The three trials enrolled a total of 139 eyes of 136 participants, of which 123 eyes were included in the final analyses. The trial on FLEK and PKP was conducted from 2005 to 2007 in the Netherlands; the other two trials were conducted in the United States and were reported in 2008 and 2009 but the study dates were not specified. Over 70% of the included participants were diagnosed with FED, and the remaining participants had other ocular conditions. There was no difference in best corrected visual acuity (BCVA) between the two groups in one study at 12 months and another at 24 months. Chances of having an irregular shape of the front of the cornea (astigmatism) was less but endothelial cell loss was higher following EK procedures than after PKP. Only one trial reported harms of the interventions, and indicated that FLEK may result in slightly more complications than PKP (for example, 8% graft failure in the FLEK group versus none in the PKP group; and 3% graft rejection in the FLEK group versus 2% in the PKP group). No trials reported information about quality of life or economic data. The quality of the evidence was not high due to some limitations with the study designs and because all trials had small numbers of participants with FED.
We identified eight RCTs with a total of 3610 people with symptomatic PAD where participants were randomised to receive an anti-hypertensive treatment for at least one month or placebo or no treatment. Four studies compared an anti-hypertensive treatment with placebo and four studies compared two anti-hypertensive treatments with each other. The studies were not combined due to the variation of comparisons and the outcomes presented. One trial with 1725 participants showed that the angiotensin converting enzyme (ACE) inhibitor ramipril was effective in reducing the number of cardiovascular events by 28% compared to placebo. In one other study using an ACE inhibitor (n = 52) the perindopril group showed a small increase in claudication distance but no change in ABI and a reduction in maximal walking distance (MWD). In patients undergoing peripheral arterial angioplasty (a procedure to open narrowed or blocked blood vessels) the results from a trial with 96 participants suggested that the calcium channel blocker verapamil reduced restenosis (new blockage of the artery) at six months. In one small study (n = 80) peripheral arterial wall thickness was similar whether men received the thiazide diuretic hydrochlorothiazide (HCTZ) or the alpha-adrenoreceptor blocker doxazosin. In another small study (n = 36) MWD was improved at 12 months in the angiotensin-II receptor antagonist telmisartan group compared to the placebo group but there were no significant differences in ABI or arterial wall thickness. Another study (n = 163) found no significant differences in intermittent or absolute claudication distance, ABI, all-cause mortality or non-fatal cardiovascular events after 24 weeks of treatment in the beta-adrenoreceptor blocker nebivolol group and the HCTZ group. A study comparing two beta-adrenoreceptor blockers, nebivolol and metoprolol, found no clear differences in intermittent or absolute claudication distance, ABI, all-cause mortality or revascularisation after 36 weeks of treatment. A subgroup analysis of PAD patients (n = 2699) in the final study revealed no significant differences in the combined endpoints of death, non-fatal myocardial infarction or non-fatal stroke with or without revascularisation between the calcium antagonist-based strategy (verapamil slow release (SR) with or without trandolapril) compared to the beta-adrenoreceptor blocker strategy (atenolol with or without HCTZ). The evidence on the use of various anti-hypertensive drugs in people with PAD is poor so that it is not known whether significant benefits or risks accrue. However, lack of data specifically examining outcomes in hypertensive PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure.
We searched for all relevant randomised controlled trials up to 14 June 2017. This systematic review included eight randomised controlled trials involving a total of 850 participants. All trials compared mechanical devices versus ligatures for appendix stump closure. Five of the eight trials compared use of clips versus ligature, two trials compared an automated stapler versus ligature, and one trial compared all three methods. Use of mechanical devices to close the appendix stump during laparoscopic appendectomy did not make a significant difference in the rate of overall complications when compared with use of a ligature, or in the rate of complications that happened during or after the appendectomy procedure. However, mechanical devices did make the operation nine minutes quicker when compared with ligatures. Mechanical devices did not make a substantial difference in overall hospital stay. We did not have enough information to reliably evaluate hospital costs, pain, or quality of life for either of these comparisons. As a result, we have not found enough evidence at present that would lead us to strongly recommend any particular method over another. More research should be undertaken to better compare available newer methods. The evidence used to derive our conclusions was generally of low quality. The studies we included for each analysis were vulnerable to different types of bias and contained inconsistencies and imprecision in their results due to small numbers of participants and events in each included study arm. It is likely that future research will substantially change our conclusions; further studies in this field are needed.
We collected all published randomized controlled trials evaluating the efficacy of NSAIDs until 24 June 2015. We included 13 trials which compared NSAIDs with placebo, other NSAIDs, other drugs or other treatment in people with chronic low back pain. Six trials compared NSAIDs with placebo, and included 1354 participants in total. Follow-up was between nine days and 16 weeks. NSAIDs reduced pain and disability in people with chronic low back pain compared to placebo. However, the differences were small: 7 points on a 100-point scale for pain intensity. Regarding disability, people receiving NSAIDs scored 0.9 points better on a 0 to 24 disability scale. The number of adverse events was not significantly different between the people receiving NSAIDs and people receiving placebo, but larger studies of longer duration would be needed to identify rare or delayed adverse events, important drug interactions and adverse events occurring with prolonged use. Different types of NSAIDs did not show significantly different effects. Three of the 13 included studies compared two different types of NSAIDs and none found any differences. NSAIDs were also compared to other drug types: paracetamol, tramadol and pregabalin. There were no differences found between NSAIDs and paracetamol and pregabalin in either effect or adverse events. A single study comparing celecoxib with tramadol showed a better global improvement in peoples using celecoxib. One trial compared NSAIDs with 'home-based exercise'. Regarding disability, people who did exercise improved more than people receiving NSAIDs, but pain scores were not statistically different. There was low quality evidence that NSAIDs are slightly more effective than placebo in chronic low back pain. The magnitude of the difference was small, and when we only accounted for trials of higher quality, these differences reduced.
We included 36 studies involving a total of 1472 participants over the age of 18 years with acute, postacute, or chronic ischaemic or haemorrhagic stroke. The mean age in the included studies ranged from 48 years to 76 years. The majority of studies were conducted in an inpatient setting. We found moderate-quality evidence that electromechanical-assisted gait training combined with physiotherapy when compared with physiotherapy alone may improve recovery of independent walking in people after stroke. We determined that for every seven patients treated with electromechanical- and robotic-assisted gait training devices, just one prevention of dependency in walking occurs. Specifically, people in the first three months after stroke and those who are not able to walk appear to benefit most from this type of intervention. The importance of the type of device is still not clear. Further research should address what frequency or duration of walking training might be most effective and how long the benefit lasts. It also remains unclear how such devices should be used in routine rehabilitation. The quality of the evidence for automated electromechanical- and robotic-assisted gait-training devices for improving walking after stroke was moderate. The quality of evidence was low for walking speed, very low for walking capacity, and low for adverse events and people discontinuing treatment.
A total of 1450 patients took part in six studies investigating colesevelam. These studies lasted 8 to 26 weeks. Only one small study compared colesevelam directly to placebo, the other five studies investigated a combination of colesevelam with other antidiabetic agents versus a combination of placebo with other antidiabetic agents. There were no two studies with the same intervention and comparison group. When added to other antidiabetic agents colesevelam showed improvements in the control of blood glucose and blood lipids. However, it is difficult to disentangle the effects of colesevelam from the other antidiabetic agents used because only one study compared colesevelam to placebo. The same is true for adverse effects: three studies reported on just a few non-severe hypoglycaemic episodes, no other serious side effects were observed. No study investigated mortality; complications of type 2 diabetes such as eye disease, kidney disease, heart attack and stroke; health-related quality of life; functional outcomes and costs of treatment. Therefore, long-term data on the efficacy and safety of colesevelam are necessary.
The authors searched for relevant medical research reports and found six randomised controlled trials involving a total of 2128 people. In each study, people with uncontrolled bleeding were randomly assigned to receive one treatment or another. Three studies were about the amount of fluid given (more or less), and three studies were about giving fluid at different times following injury (sooner or later). The authors were interested in finding out which treatments were better, to reduce deaths and to enable blood clotting. Blood clotting was measured by prothrombin time and partial thromboplastin time during fluid administration. The review of trials found that there is uncertainty about the best time to give fluid and what volume of fluid should be given. While increasing fluids will maintain blood pressure, it may also worsen bleeding by diluting clotting factors in the blood. The first version of this review was published in 2000 and included these six trials. The authors searched for new, relevant studies in 2003, 2008 and 2014 but none were found. The authors will look for studies in 2020, and any new information will be incorporated into the review.
The three included trials provided some weak and unreliable evidence for the effectiveness of Beconase® and flunisolide used topically in the nose for the treatment of intermittent and persistent allergic rhinitis in children. The review authors concluded that until more research is available, decisions on the use of topical steroids should be guided by the physician's clinical experience and patients' individual circumstances and preferences.
Two trials looked at the effect of adding bevacizumab to conventional chemotherapy in women who had just been diagnosed with ovarian cancer and had debulking surgery. Bevacizumab was given both alongside the chemotherapy, and then continued afterwards (called maintenance therapy). Taking the results of these two trials together, there was no significant benefit from adding bevacizumab to standard chemotherapy in terms of survival time, but there was fairly strong evidence that it might slow the growth of the cancer (increased progression-free survival (PFS)). However, the trials also showed that there were worse side effects in women who received bevacizumab in addition to chemotherapy (particularly high blood pressure, serious bowel problems and bleeding). One of these two trials also looked at the effect of giving bevacizumab concurrently with chemotherapy (not continuing afterwards), and found no significant improvement in either survival time or slowing cancer growth, but did find a significant increase in moderate and severe high blood pressure (hypertension). A third trial looked at adding a different agent, AMG 386, to paclitaxel chemotherapy in women with recurrent ovarian cancer. The trial compared the addition of either a higher or lower dose of AMG 386 to placebo. It found no improvement in survival with either the higher or lower dose of AMG 386, but there were suggestions that it might slow cancer growth. It did not seem to increase side effects. We identified two other trials; one comparing placebo to BIBF 1120, and the other comparing placebo to VEGF (vascular endothelial growth factor)-Trap. Neither study found evidence of slowing cancer growth/prolonging survival, or worsening side effects. However, these were both relatively small studies, which made them less likely to detect an effect that may or may not have been present. All of the included trials that we identified reported only preliminary results, which had been presented at conferences, but not yet published in full. It is thus difficult to be sure of the specific details of how these trials were performed, and therefore to assess their risk of bias. We found 12 other on-going studies that fulfilled our inclusion criteria, and some of these are expected to release preliminary results soon.
The aim of this systematic review was to analyse the benefits and harms of the different forms of vitamin D especially on cancer occurrence. A total of 18 trials provided data for this review; 50,623 participants were randomly assigned to either vitamin D or placebo or no treatment. All trials were conducted in high-income countries. The age range of the participants was 47 to 97 years and on average 81% were women. The majority of the included participants did not have vitamin D deficiency. Vitamin D administration lasted on average six years and most trial investigators used vitamin D₃ (cholecalciferol). We did not find firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. We observed decreases in all-cause mortality and cancer-related mortality among the vitamin D/D₃ treated participants in comparison with the participants in the control groups. However, using trial sequential analysis, a statistical approach to reconfirm or question these findings, we conclude that these results could be due to random errors (play of chance). We also found evidence that combined vitamin D₃ and calcium supplements increased renal stone occurrence, but it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. Moreover, these results could also be due to random errors (play of chance). A large number of the study participants left the trials before completion, and this raises concerns regarding the validity of the results. Most of the trials were judged not to be well and fairly conducted so that the results were likely to be biased (that is, possibly an overestimation of benefits and underestimation of harms). This evidence is up to date as of February 2014.
This review found 28 studies that evaluated the effects of different on-screen computer reminders. The studies tested reminders to prescribe specific medications, to warn about drug interactions, to provide vaccinations, or to order tests.  The review found small to moderate benefits. The reminders improved physician practices by a median of 4%. In eight of the studies, patients' health improved by a median of 3%. Although some studies showed larger benefits than these median effects, no specific reminders or features of how they worked were consistently associated with these larger benefits. More research is needed to identify what types of reminders work and when.
We included 18 randomised controlled trials (RCTs) with a total of 2738 participants in this review. Most studies were relatively small, with as few as 9 or 10 patients per intervention arm. The largest study had 748 patients in total. Most were conducted in tertiary referral centres in northern Europe, the US and Canada. Fourteen studies only included participants with chronic rhinosinusitis with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. The studies looked at a range of types, doses and methods of administration (e.g. spray, drops) of intranasal corticosteroids. One study (20 participants) reported no statistically significant difference in disease-specific health-related quality of life. Another measured general health-related quality of life and reported a statistically significant benefit only on a subscale for general health. Both studies recruited participants with chronic rhinosinusitis without nasal polyps. The quality of the evidence was very low (we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect). Disease severity was measured in one study (chronic rhinosinusitis without nasal polyps, 134 participants), which found no important difference. Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group. The quality of the evidence was low (our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect). When each type of symptom was measured separately (nasal blockage, rhinorrhoea, loss of sense of smell, facial pain/pressure), benefit was shown in the intranasal corticosteroids group. The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure (moderate quality evidence means we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different). There was an increased risk of nosebleeds (epistaxis) with intranasal corticosteroids (high quality evidence). However, it was unclear whether there was a difference in the risk of local (nose or throat) irritation (low quality evidence). None of the studies treated or followed up patients long enough to provide meaningful data on the risk of osteoporosis (fragile bones) or stunted growth (in children). Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life and the quality of this evidence is very low. For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of nosebleeds is increased (high quality evidence), but this included all levels of severity; for some patients small streaks of blood may not be a major concern. It is unclear whether there is a difference in the risk of local irritation (low quality evidence).
We ran an electronic search of Cochrane Schizophrenia's register of trials in April 2015, May 2017, and October 2019 for trials that randomised (allocated participants to treatment groups using a random method) people with schizophrenia to receive add-on modafinil (modafinil added to their standard care) or to receive add-on placebo. We identified 67 records that referred to 25 studies. Eleven studies met the review requirements and reported data that could be used in analyses. However, the trials included small numbers of participants and were of short duration; schizophrenia is a long-term health problem that ideally requires studies of longer duration. Our analysis of the data showed there is no clear difference between add-on modafinil and add-on placebo for improving mental state or global state, changing cognitive functioning, causing participants to leave a study early, producing adverse effects, or affecting rates of hospitalisation. However, most of these results were based on very low- or low-quality data, therefore it is uncertain if these statistical effect sizes found by our data analyses are true effects. The results of this review indicate no clear difference in effectiveness and safety between add-on modafinil and add-on placebo, however these results are not conclusive as they are based low- or very low-quality evidence. Based on the current evidence we were unable to provide an answer to our review question as to whether modafinil is better than placebo for improving the symptoms of schizophrenia, or if it is safe to use for people with schizophrenia. More high-quality research is needed.
By combining results, immunostimulants reduced 1.24 ARTIs in a six-month period, equivalent to a 39% reduction in ARTIs compared to the placebo group. Only 20 studies provided adequate data on adverse events: the most frequent were rash, nausea, vomiting, abdominal pain and diarrhea. The main limitations of this review were the poor methodological quality and diverse trial results. We conclude that ARTI-susceptible children may benefit from immunostimulants, but more high-quality studies are needed. We suggest that national health authorities conduct high-quality randomized controlled trials to assess the true effects of immunostimulant preparations.
The objective of this review was to assess if oral and intravenous steroids are equally effective and safe in aiding in the recovery from relapses. Among the pertinent literature, only five studies met the inclusion criteria, comprising a total of 215 participants. Despite some limitations in the methods used to conduct the studies (i.e. incomplete reporting of the participants who dropped out the studies and appropriateness of the sample size) and in the analysis of the data, all five studies found that there were no significant differences in term of benefits and adverse events and in the pharmacological and radiological outcomes in patients taking oral or intravenous steroids. Both treatments appear to be equally effective and safe. Based on this evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy for the treatment of MS relapses.
We identified three trials that provided some information on this topic. A total of 47 people with MRSA-infected diabetic foot infections were randomised to six different antibiotic treatments (choice of treatment determined by a method similar to coin tossing). The only outcome reported was the eradication of MRSA. The trials reported none of the other outcomes that are important for patients and healthcare funders, such as death, quality of life, length of hospital stay, use of healthcare resources and time to complete wound healing. Each trial compared different antibiotics, and in each comparison there was no difference in the effectiveness of the antibiotics in eradicating MRSA. The three trials were very small and had a number of design faults, so it is still not possible to say which antibiotic is the most effective in eradicating MRSA from non-surgical wounds. Because there were no trials at all comparing the use of antibiotics with no antibiotic we do not know whether using antibiotics at all makes a difference for people with MRSA-colonised non-surgical wounds. Further well-designed randomised controlled trials are necessary to determine the best treatment for non surgical wounds containing or infected with MRSA.
Fourteen studies met the inclusion criteria, involving a total of 2313 people. These studies varied in terms of how bad exacerbations had to be for people to be included and in terms of what other treatments were provided before IV MgSO4was given, but almost all trials gave participants at least oxygen, nebulised short-acting medications and steroid tablets or injection. Overall, IV MgSO4 reduced the need for hospital admission compared with placebo (seven fewer per 100 treated; 95% confidence interval two to 13 fewer). Not enough information was available to show whether the reduction in hospital admissions was associated with severity of the asthma exacerbation, or whether it made a difference what other treatments were given. Evidence suggests that IV MgSO4 improved some lung function parameters, but for other measures such as heart rate, variation among study findings reduced our confidence in the results. We did not find a difference between IV MgSO4 and placebo in most other measures (including time spent in the ED, respiratory rate and blood pressure), and adverse events generally were poorly reported. This review showed that IV MgSO4reduces hospital admissions and improves lung function in adults with exacerbations of asthma when other first-line medications have not relieved the acute symptoms (i.e. oxygen, inhaled short-acting medications and IV steroids). Evidence for other measures of benefit and safety was limited. Researchers should clearly define the severity of the asthma condition among people in their studies while carefully recording adverse events. This plain language summary is current as of May 2014.
This was a systematic review of 35 short-term randomised controlled trials of pharmacotherapy for PTSD (4597 participants). A significantly larger proportion of patients responded to medication (59.1%) than to placebo (38.5%) (13 trials, 1272 participants). Symptom severity was significantly reduced in 17 trials (2507 participants). The largest trials showing efficacy were of the selective serotonin reuptake inhibitors, with long-term efficacy also observed for these medications.
We searched the medical literature up to July 2013 for studies that tested the effects of exercise and reported fear of falling in community-dwelling people (i.e. who live either at home or in places of residence that do not provide nursing care or rehabilitation) aged 65 years and older. The studies compared exercise with no treatment or an alternative intervention, such as education. Summary of the evidence We included 30 studies in the review, with a total of 2878 participants whose average age ranged from 68 to 85 years. Most studies recruited mainly women. Twelve studies recruited participants at increased risk of falls and three of these recruited people who also had fear of falling. All of the studies were at some risk of bias mainly because the participants were aware what group they were in. This lack of blinding may have influenced the study results. We found low quality evidence from 24 studies that exercise interventions result in a small to moderate reduction in fear of falling immediately after the intervention. Some exploratory analyses did not enable us to determine whether this effect differed in different groups of people, such as those at high risk of falling, or with different exercise interventions, such as group or individual exercise. We are very unsure that the effect of exercise on fear of falling is maintained in the next few months after the end of the intervention. We only included studies that reported fear of falling, therefore the evidence on our other outcomes (occurrence of falls, depression, anxiety and physical activity) is only a small part of the total evidence of the effects of exercise on these outcomes. However, the evidence from nine studies included in our review showing that exercise reduced the risk and number of falls is consistent with the results of another Cochrane review testing the effects of exercise on preventing falls. The evidence on the other outcomes was far less and none of the included studies reported the effects of exercise interventions on activity avoidance or costs. Conclusion We concluded that exercise interventions in community-dwelling older people probably reduce fear of falling to a limited extent immediately after the intervention, without increasing the risk or frequency of falls. We also concluded that there is not enough evidence to determine whether exercise interventions reduce fear of falling beyond the end of the intervention or their effect on other outcomes. We encourage further research on this topic.
Not enough evidence from trials on the use of adrenaline (epinephrine) for preterm babies with poor heart rates and circulation. Sustained poor blood flow in preterm babies can lead to complications, including impaired development. Inotrope drugs, particularly dopamine and dobutamine, are commonly used to increase heart rate and blood pressure in preterm babies with poor circulation. Adrenaline (epinephrine) is another inotrope drug that can be used. The review found that there is not enough evidence from trials to show the effects of adrenaline on preterm babies with poor circulation, and more research is needed.
This review presents the effects of budesonide at different doses for people with varying degrees of asthma. In patients with mild-moderate asthma no important differences were apparent between the lowest dose (200 mcg/d) and the highest dose (1600 mcg/d) for measures of airway opening and symptoms. However, patients with more severe asthma are less likely to experience an acute worsening of their asthma control when a higher dose (1600 mcg/d) is used regularly compared to a lower dose (200 mcg/d). Future research should report results more comprehensively, and should use quality of life questionnaires.
Each study included in this review looked at a different intervention to reduce pain in mammography. The trial results show that giving women written or verbal information about the procedure prior to the mammogram can reduce pain or discomfort of the examination. Also increasing women's control of breast compression could reduce the pain they experience, though there was no change in the pain women experienced when a mammography-technologist reduced the compression force. Use of breast cushions also reduced the pain; however, it caused a poor quality of X-ray in 2% of women screened, which meant that they would need to have a further mammogram. Paracetamol taken before the procedure did not change the pain the women experienced. Further research is needed on interventions to relieve the pain and discomfort of screening mammography.
We performed a systematic search (up to 31 October 2014) for trials that compared non-platinum single-agent therapy versus non-platinum combination therapy or non-platinum combination therapy versus platinum combination therapy in patients over 70 years of age who have advanced non-small cell lung cancer. We included in the review a total of 51 studies (seven studies in the non-platinum single-agent therapy vs non-platinum combination therapy group and 44 studies in the non-platinum combination therapy vs platinum combination therapy group); however, we were able to include only 19 studies in the meta-analysis. Non-platinum single-agent versus non-platinum combination therapy We analyzed five trials involving 1294 participants. We found that these regimens are equally effective for survival. However, combinations of non-platinum agents are associated with a greater chance of decreasing tumor size. We also found that these regimens are similar regarding chance of major toxicity such as low hemoglobin levels, platelets, and white cell counts (neutrophils). Only two trials assessed the impact of treatment on quality of life, and we were not able to combine these results because of lack of information. Non-platinum therapy versus platinum combination therapy We analyzed 14 trials involving 1705 elderly participants. We found that platinum therapy is associated with longer survival and greater chance of decreasing tumor size among elderly patients. However, we found that these regimens are more toxic than those based on non-platinum agents and provide greater risk of low hemoglobin and platelet levels, fatigue, nausea or vomiting, and numbness or tingling in the hands and feet. Only five trials assessed the impact of treatment on quality of life, and we were not able to combine these results because of lack of information. Non-platinum single-agent versus non-platinum combination therapy We downgraded to low the quality of evidence on survival because different results were reported across studies, and because three included trials were stopped early, which also influenced the quality of evidence for chance of decreasing tumor size and low hemoglobin, platelet, and white cell counts. For theses outcomes, issues with study design were also a matter of concern, leading to low quality of evidence. Non-platinum combination versus platinum combination therapy We downgraded to moderate the quality of evidence on the benefit of platinum combination therapy for survival based on inclusion of nine trials that were not specifically designed for older patients. Other issues with study design influenced the quality of evidence on interval to tumor growth after start of treatment, rate of tumor shrinkage, and toxicity. Regarding low hemoglobin and platelet levels, we further reduced the quality of evidence to low because of imprecision of reported results. We recognize that other limitations such as age alone might not be adequate criteria for selection of the best treatment. Older people can be very different from one another in terms of other health conditions associated with aging. Older patients included in randomized trials were selected through strict eligibility criteria that excluded most patients with other health problems. Therefore, we believe that these results must be interpreted with clinical judgement applied regarding selection of an appropriate treatment regimen.
This review is an update of 'Topical NSAIDs for chronic musculoskeletal pain in adults', originally published in 2012. We found 39 generally high-quality studies with 10,857 participants where topical NSAID was used at least once a day. These studies tested a number of different topical drugs, mostly against a topical placebo. We were interested in participants having good pain reduction (by about half), ideally 6 to 12 weeks after treatment started. Studies that last longer are more representative of the real world, because in these chronic conditions the pain almost never goes away if untreated. We looked at individual NSAIDs to see how effective they were. Diclofenac and ketoprofen were the only two with good quality and longer duration studies, mostly in people aged over 40 years with painful knee arthritis. The comparison was between topical diclofenac or ketoprofen in a solution or gel, and the solution or gel without any drug in it (topical placebo). For diclofenac and ketoprofen, about 6 people out of 10 with osteoarthritis had much reduced pain after 6 to 12 weeks, compared with 5 out of 10 with topical placebo (moderate quality evidence). Skin reactions (mostly mild) were more common (20 in 100) with topical diclofenac than topical placebo (5 in 100); there was no difference between topical ketoprofen and topical placebo (moderate quality evidence). Other adverse events, like stomach upsets, were poorly reported in these studies, but were no different between topical diclofenac or ketoprofen and topical placebo (very low quality evidence). Serious adverse events were uncommon. We rated the quality of the evidence for topical diclofenac and topical ketoprofen compared with placebo as moderate for efficacy, and very low for harmful effects. Moderate quality evidence means that further research may change our estimate of the effect, and very low quality evidence means that we are very uncertain about the accuracy of our estimate.
For the present review, researchers in The Cochrane Collaboration reviewed the evidence about the effects of topiramate in adult patients (≥ 16 years of age) with 'episodic' migraine (headache on < 15 days per month). They examined research published up to 15 January 2013 and found 17 relevant studies. Compared with placebo, topiramate reduced the frequency of migraine headaches by approximately 1.2 per month (nine studies, 1737 participants). Patients were also about twice as likely to reduce the number of their migraine headaches by 50% or more with topiramate than with placebo (nine studies, 1190 participants). Side effects associated with topiramate were common but generally mild; topiramate can, however, cause birth defects and so should be used with caution in women of childbearing age. Further research is needed comparing topiramate with other active drugs used for preventing migraine attacks.
Two trials involving 283 women compared the effects of perineal HAase injection with placebo injection during second stage of labour and were at low risk of bias. Three trials (one three-armed trial was analysed twice) with 373 women compared the effects of perineal HAase injection during second stage of labour with no intervention. The overall results showed that perineal HAase injection had a significantly lower incidence of perineal trauma compared with control or no intervention, but there was no difference in the incidence of episiotomy, first and second degree and more severe (third and fourth degree) perineal tears. There was no clear evidence that HAase injection lowered the incidence of perineal trauma, episiotomy, first and second degree and more severe (third and fourth degree) perineal tears when compared with placebo injection. No side effects were reported in the included trials. Other measures such as perineal pain and other pre-specified secondary outcomes were not measured by the included trials. The difference in the incidence of perineal trauma may be due to bias and confounding in the non-placebo controlled comparison, this result should be interpreted cautiously. The potential use of this intervention as a method to reduce perineal trauma are yet to be determined as there was no appropriate established dose for HAase, no evidence of follow-up and side effects, and the number of high-quality trials and outcomes reported was too limited to draw conclusions on its effectiveness and safety. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries.
We searched the medical literature for evidence from trials up to 6 March 2018. We found two randomised trials that compared freezing of the whole prostate to radiation treatment. These included 307 randomised men with prostate cancer (cryotherapy 154 men, radiation 153 men). Their average age was around 70 years. These studies followed men for eight to nine years after treatment. We did not find any studies that compared freezing the prostate to surgery. Also, we did not find randomised trials that compared freezing of parts of the prostate (focal cryotherapy) to radiation, surgery or no treatment. We are uncertain of the effects of freezing of the whole prostate compared to radiation treatment on the time to death from prostate cancer, quality of life for urinary, bowel, and sexual function and serious unwanted treatment reactions. The quality of evidence was very low for all outcomes meaning that the real effect of whole gland cryotherapy may differ a lot from the findings in this review. Further research is very likely to change these findings.
A total of 34 randomised studies, involving 4001 children were identified and underwent data extraction and analysis. The most frequent comparisons were for long-term, low-dose antibiotics with no treatment (8 studies) or placebo (4 studies) and antibiotics versus surgical reimplantation of ureters plus antibiotics (7 studies). Other treatments looked at endoscopic correction by injection compared with antibiotics (3 studies), different materials for endoscopic correction (2 studies) circumcision (1 study), probiotics (1 study), cranberry product (1 study), and oxybutynin (2 studies). Meta-analysis of similar studies found that long-term low-dose antibiotic treatment compared with no treatment may lead to little or no difference in the risk for repeat UTIs in children with VUR. Associated side effects were infrequent and minor, but prophylaxis was associated with a threefold increased risk of bacterial resistance to the treatment drug in later infections. Surgery decreased the number of repeat UTIs with fever, but did not change the number of children developing UTI with illness or kidney damage. Many studies did not contribute to the meta-analysis as they failed to report relevant outcomes or were single studies examining a treatment option not used by other studies or combinations of treatments. Long-term low-dose antibiotic treatment in children with VUR makes little or no difference to the risk of repeat UTI causing a person to be unwell. Surgery may reduce the risk of repeat UTI with fever however this is based on two studies of 429 children who may not represent the majority and may not bear true in a more general group of children with VUR. Complementary therapies such as probiotics and cranberry were trialled in single or two studies and do not provide evidence of sufficient certainty to support or deny their use.
We first looked at the evidence in 2000 and this is an update of the original review. In total we found 43 studies examining 4265 people. We looked at adults with advanced gynaecological or gastrointestinal cancer who developed bowel obstruction and had either surgical or non-surgical treatment. The studies we found were of low quality and measured success and benefit in different ways. It was therefore not possible to compare these studies and conclude whether surgery was of benefit or harm in this situation. Research in this area is problematic and the type of study needed to answer this question would be very difficult to conduct.
Fluspirilene is a relatively long-acting injectable depot antipsychotic drug used for schizophrenia. We updated the original systematic review (David 1999) on Depot fluspirilene for schizophrenia with five additional studies. Twelve randomised trials are included. Study sizes are small and most were of short term duration. This cannot be very informative for a drug that is meant for long-term maintenance treatment. However, from the studies we were able to include, fluspirilene decanoate does not differ greatly from other depot antipsychotics (fluphenazine decanoate, fluphenazine enathate, perphenazine onanthat, pipotiazine undecylenate) with respect to treatment efficacy, response or tolerability. Outcomes suggest that fluspirilene does not differ significantly from oral antipsychotics or in different weekly regimens, although much cannot be inferred because of the shortage of trials.
Based on evidence from trials on HIV-negative patients with hepatitis C, the viral genotype, dose of treatment and duration of therapy may affect the treatment response. This review is the first to evaluate the antiviral effect of peginterferon, ribavirin or amantadine administered in different combinations for a patient group, which has not previously been treated for hepatitis C. A total of 14 randomised clinical trials with at total of 2269 patients have been included in this review.The present review suggests that peginterferon plus ribavirin may also be considered if patients have HIV. The dose of peginterferon was similar to that assessed in trials on patients without HIV (180 microgram or 1.5 microgram/kg once weekly), but the dose of ribavirin was somewhat lower in most trials (800 mg daily). There were considerable differences between the trials possibly related to the dose and duration of treatment or the proportion of patients with different hepatitis C virus genotypes. The benefit of treatment was seen when assessing the proportion of patients with a sustained loss of the hepatitis C virus from the blood and the proportion with improved liver biopsies. No significant differences were seen in clinical outcome measures, including mortality (1%, irrespective of treatment). There were several adverse events. Fatal lactic acidosis and liver failure occurred. Other adverse events included anaemia and flu-like symptoms that occurred more frequently among patients receiving peginterferon plus ribavirin. No significant differences were seen regarding the risk of depression, mortality, and progression to cirrhosis or to AIDS. Additional randomised trials are necessary to assess the effect in HIV and HCV co-infected patients of peginterferon plus ribavirin in relation to the duration of therapy, especially in patients with hepatitis C genotype 2 or 3. Additional trials comparing peginterferon plus ribavirin versus interferon plus ribavirin or peginterferon alone do not seem warranted.
We included 12 trials with 695 participants. Five of the 12 studies included participants awaiting planned heart surgery, and seven studies included participants awaiting planned major abdominal surgery. The evidence is current to October 2014. This review showed that training of breathing muscles before surgery reduced the risk of some lung complications (atelectasis and pneumonia) after surgery and the length of hospital stay, compared with usual care. However, the effect of this training on in-hospital death after surgery is unclear and needs further investigation. The trials did not report any undesirable effects associated with training of breathing muscles, and no study reported on costs resulting from breathing training using a device. Although the available evidence is insufficient in terms of the quality and size of trials, we can conclude that training of breathing muscles before surgery prevents lung complications after surgery. This training is easily performed at home under the supervision of a physiotherapist. The training of breathing muscles therefore appears to be a suitable option as one of the preparations for planned surgery, especially for adults awaiting high-risk heart and abdominal surgery. Other surgeries, such as oesophageal resection (removal of part of the gastrointestinal tract 'food pipe'), should be evaluated; cost-effectiveness and patient-reported outcomes should be reported. The potential for overestimation of treatment effect needs to be considered when interpreting the present findings, as the quality of evidence is low to moderate.
In this review we have studied the effectiveness of LAM as a contraceptive method in fully breastfeeding women in comparison to breastfeeding women without any support. We found no clear differences in effectiveness (pregnancy) between women using LAM and being supported in doing so, and fully breastfeeding amenorrheic women not using any method. Apart from this we recommend breastfeeding itself from a public health point of view.
We conducted a literature search up to September 2015 and nine studies were eligible for inclusion according to our selection criteria. The nine studies reported data on 735 participants and investigated probiotics for preventing UTI: seven studies involved women or girls with recurrent UTIs, one looked at children with abnormal urinary tracts, and one investigated UTI in healthy women. Generally, studies were poor quality with high risk of bias. Aside from the different populations, there were also many different species of probiotics used, different dosage forms such as vaginal and oral, and probiotics were given for varying lengths of time. All of these factors may have affected our results. Most studies did not collect information on adverse effects so we were unable to estimate any harms associated with probiotic therapies. We found no significant reduction in the risk of recurrent symptomatic bacterial UTI between patients treated with probiotics and placebo and no significant reduction in the risk of recurrent symptomatic bacterial UTI was found between probiotic and patients treated with antibiotics. The currently available evidence shows no reduction in UTI using probiotics.
Forty studies (3764 patients) were identified. Plasma exchange reduces the risk of end-stage kidney disease in patients presenting with severe acute kidney failure (AKI). The use of pulse cyclophosphamide results in good remission rates but there was an increased risk of relapse. Other appropriate induction agents include rituximab and mycophenolate. Azathioprine is effective as maintenance therapy once remission has been achieved. A lower dose of steroids is just as effective as high dose and may be safer, causing fewer infections. One study shows that a new complement inhibitor can be used to replace steroids in the initial treatment of vasculitis. These are early data. The drug is likely to be very expensive so its place in treatment is not yet clearly defined. Mycophenolate mofetil has also been tested in maintenance treatment and was found to result in a higher rate of disease relapse, when compared to Azathioprine. Methotrexate and leflunomide are useful in maintenance therapy but their relative effectiveness are not clearly defined. Patients on immunosuppression for up to four years after diagnosis have a lowered relapse rate to those in whom treatment is ceased by three years. Plasma exchange was effective in patients with severe AKI. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is used as standard induction treatment, rituximab and mycophenolate mofetil were also effective. Lower dose steroids can now be safely used in initial treatment protocols. Azathioprine, rituximab, mycophenolate, methotrexate and leflunomide are effective maintenance therapy. More trials are required to understand these drugs and new therapies for quickly treating renal vasculitis.
Authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 19 August 2013. It includes 30 studies published from 1990 to 2012 in which 14,835 participants were randomised to receive a triclosan/copolymer containing fluoride toothpaste or a fluoride toothpaste that did not include triclosan/copolymer. The toothpaste that was used in most of the studies is sold by the manufacturer Colgate. The evidence produced shows benefits in using a triclosan/copolymer fluoride toothpaste when compared with a fluoride toothpaste (without triclosan/copolymer). There was a 22% reduction in plaque, a 22% reduction in gingivitis, a 48% reduction in bleeding gums and a 5% reduction in tooth decay. There was insufficient evidence to show a difference between either toothpaste in preventing periodontitis. There was no evidence of any harmful effects associated with the use of triclosan/copolymer toothpastes in studies up to three years in length. The evidence relating to plaque and gingivitis was considered to be of moderate quality. The evidence on tooth decay was high quality, while the evidence on periodontitis was low quality.
We reviewed the medical literature up to July 2013 and identified four randomised controlled trials that investigated early (permanent removal of dressings within 48 hours of surgery) versus delayed removal of dressings (permanent removal of dressings after 48 hours of surgery with interim changes of dressing allowed) in people with surgical wounds. The levels of bias across the studies were mostly high or unclear, i.e. flaws in the conduct of these trials could have resulted in the production of incorrect results. A total of 280 people undergoing planned surgery were included in this review. One-hundred and forty people had their dressings removed within 48 hours following surgery and 140 people had their wounds dressed beyond 48 hours. The choice of whether the dressing was removed early (within 48 hours) or retained for more 48 hours was made randomly by a method similar to the toss of a coin. No significant differences were reported between the two groups in terms of superficial surgical site infection (infection of the wound), superficial wound dehiscence (partial disruption of the wound that results in it reopening at the skin surface) or the number of people experiencing serious adverse events. There were no deep wound infections or complete wound dehiscence (complete disruption of wound healing, when the wound reopens completely) in the studies that reported these complications. However, the studies were not large enough to identify small differences in complication rates. None of the studies reported quality of life. Participants in the group that had early removal of dressings had significantly shorter hospital stays and incurred significantly lower treatment costs than those in the delayed removal of dressings group, but these results were based on very low quality evidence from one small randomised controlled trial. We recommend further randomised controlled trials are performed to investigate whether dressing of wounds beyond 48 hours after surgery is necessary, since the current evidence is based on very low quality evidence from three small randomised controlled trials.
Four randomised controlled trials (RCTs) were identified. All four RCTs were in the US and with adolescents described as deprived, and most were minority group adolescents. Two RCTs tested the "Across Ages" mentoring programme, one the Big Brothers/Big Sisters mentoring programme, and one an intervention with adolescents whose parents were HIV+. Two RCTs found that mentoring reduced rates of initiation of use of alcohol, and one reduced initiation of use of drugs. No adverse effects were identified. The relative youth of three of the samples made it unlikely that the interventions would be effective due to low baseline rates of usage. The studies assessed formal programmes, and as most mentors are informal their work remains un assessed.
This is an update of a previous review that included studies on migraine and tension-type headache. The original review has been split into two separate reviews: this update addresses only studies on tension-type headache, while a second focuses on migraine. When we updated this review (November 2014), we identified two new studies. Six studies were already included in the previous version of the review. Overall, we analysed a total of 412 adults participants. All the studies had a small number of participants and were conducted over a period of two to four months. Only a few were of high quality. Results suggest that SSRIs or SNRIs are no better than placebo (sugar pill) in reducing the number of days with tension-type headache. There were no differences in minor side effects between participants treated with SSRIs or SNRIs versus those treated with placebo. SSRIs and SNRIs do not seem to offer advantages when compared to other active treatments, specifically the tricyclic antidepressant, amitriptyline. The participants treated with SSRIs or SNRIs suffered fewer minor side effects than those who took amitriptyline, however the number of people who stopped taking one drug or the other due to side effects was approximately equal. These results are based on poor quality, small, short-term trials (no more than four months). We did not find a study comparing SSRIs or SNRIs with other medications (e.g. botulinum toxin) or non-drug therapies (e.g. psycho-behavioural treatments, manual therapy, acupuncture).
Only amantadine has been tested in randomised clinical trials including participants with chronic hepatitis C. The main goal of these trials was to investigate whether amantadine as a single therapy or amantadine in combination with other antiviral therapy, compared with placebo or no intervention (with or without antiviral therapy), could increase the proportion of patients with virus eradication from the blood. This review evaluates whether amantadine has any beneficial or harmful effect in patients with chronic hepatitis C. The primary outcomes were all-cause mortality or liver-related morbidity (combined outcome) and adverse events. The review includes 41 randomised clinical trials with a total of 6193 patients. This review shows that there seems to be no significant benefit of amantadine on hepatitis C-infected patients regarding all-cause mortality or liver-related morbidity. We were unable to assess the effect of amantadine on quality of life due to lack of data from the trials. Furthermore, amantadine did not increase the proportion of patients with a sustained virological response which is clearance of the virus from the blood six months after treatment. We considered all the included trials to have a high risk of bias. Accordingly, the evidence from this review does not support the routine clinical use of amantadine. There is some justification for amantadine to be used in future randomised clinical trials. We found no randomised clinical trials assessing other aminoadamantanes, for example rimantadine.
In this review we analysed the effectiveness of functional analysis-based interventions for challenging behaviour in dementia. We found eighteen randomised controlled trials suitable for analysis in all four types of care settings. The majority were in family care settings and there were surprisingly few care home based studies. Most evaluated broad programmes of care, where FA was just one component of a wide range of other interventions. This made it hard to determine the real effect of FA for the management of challenging behaviour in dementia. However, positive results were noted in the frequency of the person’s reported problem behaviours and the caregiver’s reaction to them. No significant effects were found for incidence or severity of mood and other problem behaviours. Similarly, no significant effects were found for caregiver mood or burden. Whilst it is too early to reach a firm conclusion on the evidence for FA in the management of challenging behaviour in dementia, we note emerging beneficial effects on challenging behaviour where multi-component psychosocial interventions have used FA as part of the programme of care.
Four studies (with a total of 528 participants) were identified that met the inclusion criterion of comparing mucolytic treatment versus no mucolytic treatment. All studies were conducted in adults. One study considered bromhexine versus placebo, two compared RhDNase versus placebo (one for a period of two weeks and the other over a period of 24 weeks) and the fourth compared erdosteine with physiotherapy versus physiotherapy alone in elderly patients. The small number of studies available for review and their different designs meant that only descriptions of the individual studies were possible with very limited opportunities for combining the studies in single analyses. No strong evidence is available to support the use of these drugs in people with bronchiectasis (from causes other than cystic fibrosis); however it is not possible to draw any clear conclusions, as so few studies have been reported. Details of the way patients were allocated to receive or not receive mucolytics were not clearly described in any of the four studies. This was considered carefully in the review in relation to our level of uncertainty in interpreting the results. When this is taken into account, together with the imprecision of the results, estimates of the usefulness of mucolytics as treatment were generally judged to be of low quality in relation to (non–cystic fibrosis) bronchiectasis.
This review only identified two trials which compared the impact of using three or more doses of sulphadoxine-pyrimethamine to using only two doses. Using three or more doses was more effective at preventing the presence of malaria parasites in the placenta and in the peripheral blood of the pregnant woman than using the standard two doses only. Also, children born to HIV-positive pregnant women who used three or more doses of sulphadoxine-pyrimethamine weighed more than those born to mothers who used only the standard two doses. Although more frequent doses of this drug are effective in preventing malaria, HIV-positive pregnant women with low CD4 count can not use the drug since the current policy requires that they use co-trimoxazole (Bactrim®) to prevent opportunistic infections. There is need, therefore, to investigate alternative drugs and regimens in preventing malaria in HIV-positive pregnant women.
Eleven studies (involving 509 participants) were included in this review. Several antiglucocorticoid-related drugs were examined, including dehydroepiandrosterone (DHEA) (n = 5), mifepristone (n = 4), dexamethasone (n = 1) and ketoconazole (n = 1). All participants were adults with a diagnosis of schizophrenia, schizoaffective disorder or psychotic depression. Most trials examined giving antiglucocorticoid drugs as an additional part of regular treatment. Available data from these trials revealed no effects for overall psychotic symptoms, 'positive' symptoms or 'negative' symptoms. One large trial comparing mifepristone versus placebo as the sole treatment revealed a significant difference in the proportion of people responding to treatment with mifepristone versus placebo. This effect was not seen immediately but 21 days after the intervention was begun. Adverse effect data varied. When individual anticorticoids such as mifepristone and DHEA were compared with placebo, the incidence of side effects was similar between groups; however, pooled data on various antiglucorticoids given as an adjunct to combination treatment showed that antiglucocorticoids increased incidence of side effects than placebo. In summary, very few trials are under way, and most involve a small number of people. Limited available data do not provide enough evidence to support the use of antiglucocorticoid treatments for psychosis; additional trials are needed.
This review focuses on the effects of horticultural therapy for people with schizophrenia. An electronic search for relevant randomised trials was run in January 2013. Only one trial was included, it randomised a total of 24 people with schizophrenia to received either their standard care plus horticultural therapy or standard care only. The trial only lasted 2 weeks (10 consecutive days) with no long-term follow-up. There are few results and the quality of evidence was rated by the review authors to be very low quality. Some of the information from this one study favoured horticultural therapy but there is insufficient evidence to draw any conclusions on benefits or harms of horticultural therapy for people with schizophrenia. More large, better conducted and reported trials are required to determine the effectiveness and benefits of horticultural therapy. This plain language summary has been written by a consumer Ben Gray, Service User and Service User Expert, Rethink Mental Illness.
This review has examined drug treatment for fatigue as it represents one of the ways this problem can be tackled. The review authors looked at trials in all types of cancer and at all stages of treatment. Fifty studies met the inclusion criteria but only 31 (7104 participants) were deemed suitable for detailed analysis as they explored fatigue in sufficient detail. They found mixed results with some drugs showing an effect on fatigue - most notably drugs that stimulate red blood cell production and also drugs that improve levels of concentration. Methylphenidate, a stimulant drug that improves concentration, is effective for the management of cancer-related fatigue but the small samples used in the available studies mean more research is needed to confirm its role. Erythropoietin and darbopoetin, drugs that improve anaemia, are effective in the management of cancer-related fatigue. However safety concerns and side effects from these drugs mean that they can no longer be recommended to treat cancer fatigue.
It was difficult to properly assess the quality of the included trials because of poor reporting. We considered there to be a serious risk of bias due to poor study methods, and further uncertainty about the results because the studies were so small. We also considered the studies to be too short to adequately address our research question. Due to these factors, we considered the quality of the evidence to be very low. Given the limited amount of evidence of very low quality, we were not able to draw any conclusions about the effect of L-carnitine on cognitive function or its safety in healthy people. Larger, better-quality studies conducted over a longer period of time are needed to answer our review question.
This review of 18 studies with 549 relevant participants looked at whether performing identical activities with both arms at the same time (simultaneous bilateral training) could improve performance in daily (or extended daily) activities, movement of the arm and/or reduce arm impairments. In comparison with usual care, bilateral training had no effect on performance in activities of daily living, functional movement of the arm or hand, performance in extended activities of daily living or motor impairment outcomes. In comparison with other arm interventions, bilateral training had no effect on performance in activities of daily living, functional movement of the arm or hand or motor impairment outcomes. One study found that people who undertook bilateral training showed less improvement in performance in extended activities of daily living than people doing another arm intervention. The evidence in this area is limited. Further research is needed to determine the effects of bilateral training.
Randomized placebo-controlled studies that evaluated the effect of daily intake of capsules containing omega-3 fatty acids to maintain remission in Crohn's disease were reviewed. Six studies including 1039 patients were included in the review. A pooled analysis of six studies suggests a marginal benefit for omega 3 fatty acids over placebo (i.e. fake medicine) in preventing relapse of disease at one year. However, these results need to be interpreted with caution due to differences across the studies in terms of induction of remission regimens (e.g. surgical remission versus drug therapy) patients (e.g. adult versus pediatric patients) and medication regimens (e.g. some studies used different placebos), the possibility of publication bias (i.e. only studies with positive results are published) and low methodological quality in four studies in the pooled analysis. When the two largest and highest quality studies were pooled the results showed no benefit to omega-3 treatment over placebo. There were no serious side effects in any of the studies. Common side effects included unpleasant taste, bad breath, heartburn, nausea and diarrhea. Evidence from two large high quality studies suggests that omega 3 fatty acids are probably ineffective for maintenance of remission in CD. Omega 3 fatty acids appear to be safe although they may cause diarrhea and upper gastrointestinal tract symptoms.
In nine trials we observed that antibiotic prophylaxis is effective in preventing infectious complications (bacteriuria, bacteremia, fever, urinary tract infection, sepsis) and hospitalization following prostate biopsy. Several classes of antibiotics are effective for prophylaxis in prostate biopsy, with the quinolones the best analysed class. There are no definitive data to confirm that antibiotic for long-course is superior to short-course treatment, or that multiple-dose treatment is superior to single-dose treatment.
Study characteristics: We found 15 relevant studies with 1926 participants. The trial size varied from 20 to 598 patients and the duration of the included studies ranged from seven days to 42 weeks. Most studies compared corticosteroids, particularly dexamethasone, to standard therapy. Key results and quality of the evidence: Overall, we found that the current evidence is based on studies that contain only a small number of patients. The following conclusions can be made from the available evidence: 1) the evidence for the efficacy of corticosteroids for pain control in cancer patients is weak (GRADE quality of evidence for pain outcome was low); 2) significant pain relief was noted in some studies, albeit only for a short period of time; this could be important for patients who have only a short time to live; 3) overall, more studies found corticosteroids not to be of benefit; 4) it was not possible to determine whether steroids are more effective for pain in specific cancers; and 5) the side effect profile of steroids, especially in the longer term, is not well described.
Antiviral drugs are often used, usually in conjunction with steroids, to treat sudden hearing loss of unknown cause, based on the theory that the deafness is caused by a viral infection. We searched for randomised controlled trials (RCTs) which compared treatment of sudden hearing loss with antiviral drugs (either alone or in combination with another treatment) with placebo or no antiviral drug, in patients of any age. We found four RCTs (257 patients). The overall risk of bias in the studies was low. All four trials compared steroid treatment (either alone or plus a placebo drug) with steroid plus antiviral treatment. None of the trials found a statistically significant difference between groups. No trial documented any serious adverse effects related to using antiviral treatments. One study reported slight to moderate nausea equally in the acyclovir and placebo groups (one patient in each), both attributable to the steroid treatment. Another reported insomnia, nervousness and weight gain with valacyclovir (number not specified). The effectiveness of antiviral drugs in the treatment of sudden hearing loss of unknown origin is questionable. Certainly, this review of the clinical trials did not identify any substantial evidence to support their use. Further research is required with larger patient numbers and standardised inclusion criteria, antiviral regimes and outcome measures.
We found no randomised controlled trials (RCTs) in the original review or when searches were updated in 2010 and 2012. Local injections of corticosteroid and surgical operations were found to be effective treatments in observational studies. However, a single observational study also showed that meralgia paraesthetica improved spontaneously in the majority of cases. RCTs of treatments for meralgia paraesthetica are needed.
However, we did identify two randomised controlled trials looking at birth-related outcomes among women who were monitored using a CTG with an ES compared to women who were monitored using CTG without an ES. Although the review identified two eligible randomised controlled trials that were at a low risk of bias, only one trial (involving 220 women) examined the outcomes of interest in this review. Data relating to death of the baby within the first 28 days of life (early neonatal death) was unavailable but the study reported that none of the babies died before being born (fetal deaths). There was no strong evidence that CTG with an ES reduces the likelihood of caesarean delivery, forceps-assisted vaginal birth or adverse baby outcomes (such as fetal acidaemia, neonatal seizures, brain injury due to lack of oxygen (hypoxic ischaemic encephalopathy), Apgar score less than seven at five minutes or admission to the neonatal intensive care unit). These results should be interpreted with caution since the trial was underpowered as too few women were included in the trial to detect modest differences in adverse outcomes. Larger randomised controlled trials are necessary to see if CTG with an ES reduces adverse outcomes for women and their babies during the birth.
The review of 21 trials (2588 patients) found that the tested drugs did not reduce deaths. There was a small reduction in the need for blood transfusions, corresponding to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile.
Different studies done in babies have shown that breastfeeding is a good way to reduce the pain babies feel when subjected to minor painful procedures. These studies have been done in full-term babies and they have shown that breastfeeding is effective by demonstrating that it reduces babies' crying time and reduces different pain scores that have been validated for babies. Breast milk given by syringe has not shown the same efficacy as breastfeeding itself. No studies have been done in premature babies, and so new studies are needed to determine if the use of supplemental breast milk in these small babies is effective in reducing their pain.
The review authors assessed the effect of these medicines on pain and their side effects. Based on 5 out of 11 included trials there were some beneficial effects of antipsychotics in the treatment of acute and chronic pain. Analysis of these studies showed a significant reduction in pain after administration of the antipsychotic compared to placebo or another medicine, however these results were based on small studies and therefore they may be unreliable. It is also important to consider the unwanted effects that these medicines might cause.
The review authors searched the medical literature and contacted experts to find studies on CDSS used with newborns. They identified three randomised controlled studies that met the criteria for the review. Two of these three studies were on computer-aided drug prescribing and one was on computerized physiological monitoring of newborns. One of the studies on computer-aided prescribing showed that the CDSS used resulted in fewer drug dosage errors. The studies found no other benefits. The studies did not consider long-term outcomes in the newborns, just short-term effects. Also, with rapid changes in computer technology, current CDSS are more advanced than those used in the three studies. The Cochrane review authors conclude that there is not enough data to determine whether or not CDSS are beneficial for newborn care.
The evidence is current to January 2018. We found 12 studies involving 1121 women with uncomplicated pregnancies. We did not specifically assess the impact of the funding sources on the studies. The people taking part in the trials we looked for (known as randomized controlled trials) are randomly assigned to either the group receiving the treatment under investigation or to a group receiving standard treatment as the control. This is to reduce any bias that either the investigators or the participants of the trial may have. We found that automated mandatory bolus decreases the risk of breakthrough pain (pain requiring medical intervention from an anaesthesiologist) compared with basal infusion during childbirth. It does this without increasing the risk of a caesarean section; the risk of instrumental delivery (whether the obstetrician intervenes to assist delivery using an obstetric forceps or vacuum device); or the duration of childbirth. It may also reduce the dose of medication required on a per hourly basis. In addition, five of seven studies found that mothers preferred the automated mandatory bolus over basal infusion. The evidence was of moderate-certainty for all the outcomes we measured, with the exception of the risk of caesarean delivery and risk of instrumental delivery, which had only low-certainty evidence.
We found three randomised studies (randomised controlled trials (RCTs) where people are allocated at random i.e. by chance alone) involving a total of 613 women. Two studies tested methotrexate in all women with a CM and one study tested dactinomycin in women with a CM who were at a high risk of getting GTN. The two methotrexate studies are older studies that used relatively poor research methods, therefore their findings cannot be relied upon. Overall the review findings suggest that P-Chem reduces the number of women developing cancer after molar pregnancy; however, this is probably only true for women with high-risk moles (i.e. CM). In addition, P-Chem might make the time to diagnose the cancer longer and might increase the number of anti-cancer treatments needed to cure the cancer if it develops. We were unable to assess the short- and long-term side-effects of P-Chem in this review because there were not enough available data; however, we are concerned that the five- and eight-day courses of P-Chem used by researchers in these studies are too toxic to be given to women routinely. We consider this evidence to be of a low to very low quality. This conclusion is based on our assessment that two of the included studies were of poor methodological quality and at a high risk of bias; the third study was of a good quality but consisted of only 60 participants. Currently there is insufficient evidence to support giving anti-cancer drugs to women with molar pregnancies. However, GTN is almost always cured with modern care and P-Chem for molar pregnancy would only reduce the risk of needing full-scale chemotherapy, but would not remove that risk. In addition, it would not change the need for careful monitoring and follow-up of women with hydatidiform moles.
We searched the literature to August 2015 and included nine studies that analysed 634 participants; durations of studies ranged from 4 and 24 weeks. The interventions included calcium-enriched bread, low phosphorus intake, low protein intake, very low protein intake, post-haemodialysis supplements and low lipid diet. Only one study reported death; none of the included studies reported cardiovascular events or fractures. One study reported adverse events. There was insufficient reporting of design and methodological aspects among the included studies to enable robust assessment of risk of bias. We found scant evidence to suggest that restricting protein or phosphorus in the diet may have positive effects for people with CKD. Evidence from one small, low quality study suggested that calcium-enriched bread may help to increase calcium and decrease phosphorus and the calcium × phosphate product. Evidence was assessed as low quality, and was insufficient to inform clinical decision-making about the value of dietary modification for people with CKD-MBD. None of the included studies reported our primary outcomes of cardiovascular events or fracture; only one study reported adverse events.
We searched medical databases for studies of dipyrone used to treat pain following surgery in adults and compared with placebo (a pretend treatment). The medicines could be given by mouth, into a vein, into a muscle, or into the rectum. The evidence is current to 11 August 2015. We found eight studies, involving 809 participants treated with dipyrone, placebo, and various other painkillers. The studies were all small, but otherwise of moderate to good quality. A single 500 mg dose of dipyrone provided effective pain relief (50% or more reduction in pain over four to six hours) for 7 in 10 (70%) participants, compared with 3 in 10 (30%) with placebo (five studies, 288 participants in the comparison; moderate quality evidence), and fewer participants need additional painkillers within four to six hours (7% with dipyrone, 34% with placebo; four studies, 248 participants; low quality evidence). There were too few data to compare dipyrone directly with other painkillers. There was too little information available to draw any conclusions about other doses and ways of giving dipyrone used in these studies, or about the number of people who had side effects. The studies reported no serious side effects or people withdrawing from the studies because of side effects, although not all studies provided information on these outcomes.
The review authors identified eight controlled trials that randomly allocated a total of 269 participants from five different countries to receive intravenous naftidrofuryl, other treatments, and placebo alone or with another treatment. There was no clear indication that short-term intravenous naftidrofuryl significantly improves either symptoms of ischaemic rest pain or skin necrosis. Treatment with naftidrofuryl tended to reduce pain, measured using a scale or with analgesic consumption, and improve rest pain and skin necrosis but the effects were not clear (statistically significant). The trials were generally of low methodological quality, included small numbers of predominantly elderly participants with varying levels of severity of critical limb ischaemia and used different measures of effect. The duration of treatment was short, from three to 42 days, most often seven days. Other treatments were haemodilution, anti-coagulant medication, prostaglandins, bed rest and reflex heating, and gingko biloba. Side effects included mild blood clotting (thrombophlebitis) at the injection site and in one trial two participants experienced renal insufficiency. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects.
The authors of this Cochrane review looked for studies which showed how effective visibility aids are for protecting pedestrians and cyclists. They focused their search on a type of study called a randomised controlled trial, which compares two similar groups of people who only differ on the issue being studied, for instance, the rate of crashes in communities with and without introduction of visibility aids. The authors found no studies that compared number of crashes but to date they have found 42 studies which compare driver detection of people with or without visibility aids. These studies showed that fluorescent materials in yellow, red and orange improved driver detection during the day; while lamps, flashing lights and retroreflective materials in red and yellow, particularly those with a 'biomotion' configuration (taking advantage of the motion from a pedestrian's limbs), improved pedestrian recognition at night. Although these visibility measures help drivers see pedestrians and cyclists, more research should be done to determine whether the increased visibility actually does prevent deaths and serious injuries.
Two relevant trials with 167 patients were identified. The limited data suggest that a gland specific lower dosage of radioiodine treatment is potentially effective for pediatric GD, but a significant higher incidence of hypothyroidism compared with ATD was observed. However, all of the analysed studies were of low quality. No trial evaluated mortality, health related quality of life, economic outcomes or compliance with treatments.
Guidelines for the treatment of asthma recommend that patients be educated about their condition, obtain regular medical review, monitor their condition at home with either peak flow or symptoms and use a written action plan. This is known to improve health outcomes when compared to usual medical care. A number of variations on optimal self-management have now been described. This review examines the efficacy of some of these options. The results showed that self-adjustment of medications according to a written action plan gave a similar improvement in health outcomes to adjustment of medications by a doctor. Either symptom diaries or peak expiratory flow monitoring may be used for monitoring asthma and reducing the intensity of the education appears to dilute the effect.
This review examined trials of interventions to improve the safe disposal of human faeces to prevent diarrhoea. In low-income settings, among the estimated 2.6 billion people who lack basic sanitation, this mainly consists of introducing or expanding the number and use of latrines and other facilities to contain or dispose of faeces. We identified 13 studies of such interventions involving more than 33,400 people in six countries. These trials provide some evidence that excreta disposal interventions are effective in preventing diarrhoeal diseases. However, major differences among the studies, including the conditions in which they were conducted and the types of interventions deployed, as well as methodological deficiencies in the studies themselves, makes it impossible to estimate with precision the protective effective of sanitation against diarrhoea. Further research, including randomized controlled trials, is necessary to understand the full impact of these interventions.
This review compared the effectiveness of IV chemotherapy to chemotherapy administered directly into the peritoneal cavity (intraperitoneal, or IP). The evidence suggests an improvement in survival if some of the chemotherapy is administered via the intraperitoneal route. The disadvantage is an increase in adverse effects principally relating to the presence of a peritoneal catheter, including pain, catheter blockage, gastrointestinal effects and infection.
This review includes 11 randomised controlled trials involving 2635 women. The trials compared carbetocin against either oxytocin or syntometrine given after delivery, vaginally or by caesarean section. The comparison between intramuscular carbetocin and oxytocin showed that there was no difference in the risk of heavy bleeding, but that women who received carbetocin were less likely to require other medications to produce uterine contractions following caesarean sections. Comparisons between carbetocin and syntometrine showed that women who received carbetocin had less blood loss compared to women who received syntometrine after vaginal delivery, and were much less likely to experience side effects such as nausea and vomiting. The incidence of hypertension at 30 and 60 minutes post delivery was also significantly lower in women who received carbetocin compared to those who received syntometrine. Five of the 11 studies were known to be supported by a pharmaceutical company.
We searched the international literature up to March 2015 for studies that compared any intervention designed to address and counsel people with heart disease in relation to sexual problems with usual care. Three randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) that included 381 participants in total met our inclusion criteria. The interventions tested in these studies were quite different from each other. All studies included people who had been admitted to hospital with a heart attack. These studies do not provide strong evidence that sexual counselling can improve sexual outcomes for people with heart disease or their partners. One study, which reported the effects of an intensive intervention, involved five hours of sexual counselling provided by a psychotherapist. It reported improved sexual functioning and satisfaction, and reduced length of time taken for people to return to sexual activity following a cardiac event, in people that received the intervention compared to usual care. The other two studies reported no differences between people that received the intervention and usual care on these outcomes (both studies measured rate of return to sexual activity following a cardiac event; one of these two studies measured sexual functioning and satisfaction). There was no evidence that sexual counselling has an effect on quality of life (measured in one study) or marital satisfaction (measured in one study). One study found that patients who received a 15-minute sexual counselling educational video plus written material had higher levels of anxiety than usual care, as well as better knowledge about sex after a heart attack, one month after their cardiac event, but not at any other timepoints. The evidence was of very low quality. We judged the included studies to be at high risk of bias and study results were poorly reported. Bearing this in mind, the results of this review should be interpreted with caution.
All participants in these RCTs received a drug aimed at suppressing the immune response (cyclosporine or tacrolimus). The study by Perkins and coworkers was funded by public and industry sources. The study by Kiehl and coworkers was funded by public sources. The funding source for the study by Bolwell and coworkers was not specified. Our results show no clinically meaningful difference between mycophenolate mofetil and methotrexate on length of survival, incidence of GVHD, disease relapse, or treatment-related death. People treated with mycophenolate mofetil had a shorter time to make new platelets (cells that help the blood to clot) from the donor cells compared with people treated with methotrexate. In addition, in terms of side effects, people treated with mycophenolate mofetil were less likely to have severe mucositis (inflammation of the mucus membranes), require parenteral nutrition (feeding through a vein), or pain medication. None of the included studies reported any data related to quality of life. In summary, mycophenolate mofetil and methotrexate both remain acceptable medications for the prevention of GVHD; however, mycophenolate mofetil seems to be associated with a smaller incidence of harms such as severe mucositis and related supportive care. The overall quality of evidence was low.
This review of trials did not find any reliable evidence for the treatment of TEN. The only trial available used thalidomide, but this trial did not show any benefit from treatment compared against placebo but highlighted increased chances of dying from the treatment. Thalidomide is not safe or effective for the skin condition toxic epidermal necrolysis, but there is not enough evidence to show which treatments are effective.
This is an updated version of a review that was first published in 2009. Since undertaking this review, we have searched the literature three times (2008, 2012 and 2016), and have identified seven completed randomised controlled trials (RCTs) and four ongoing trials. The completed trials compared three different treatment methotrexate regimens with two different actinomycin D regimens that differed by drug dose and dosing frequency. We assessed these trials as being at low to moderate risk of bias. We extracted and pooled data where possible, grouping the studies according to the treatments compared in the studies. What did we find? Overall, and for each treatment regimen compared, the review evidence shows that actinomycin D is probably more likely to achieve a cure in the first instance than methotrexate, and less likely to fail. Side-effects were reported to be relatively mild with either treatment and the most commonly experienced side-effects among women in the studies were nausea, fatigue and anaemia. However, the evidence on side-effects and serious adverse events is uncertain. Low-certainty evidence suggests that severe adverse events may be more common with actinomycin D, particularly with the five-day regimen. Conclusions Actinomycin D is probably a more effective treatment than methotrexate but the evidence on side-effects and severe adverse effects is uncertain and more evidence is needed. More evidence is also needed on the effects of these treatments on future fertility. Four RCTs comparing methotrexate and actinomycin D regimen are currently underway and these will make an important contribution to this field.
Five studies involving 187 females with an age range of 15 to 40 years were included in this review. Oral isoxsuprine was examined in two studies; terbutaline oral spray, ritodrine chloride and oral hydroxyphenyl-orciprenalin were compared with placebo in a further three studies. All of the studies were conducted over 30 years ago and none were of high quality. None of these medications, other than isoxsuprine combined with acetaminophen and caffeine, were reported to have any beneficial effect. Side effects with these medications were reported in up to a quarter of the participants and included nausea, vomiting, dizziness, quivering, tremor and palpitations. At present there is insufficient evidence to allow confident decision-making about the use of beta2-adrenoceptor agonists for dysmenorrhoea.
As only randomised controlled trials (RCTs) comparing groups with and without a weight-reducing diet can answer these issues, we only included RCTs in our systematic review. Thirty articles reporting on eight studies met the inclusion criteria. The 8 included studies involved a total of 2100 participants with high blood pressure and a mean age of 45 to 66 years. Mean treatment duration was 6 to 36 months, and there was little or no information about deaths or other long-term complications. Three of eight studies provided effects on systolic and diastolic blood pressure, suggesting that weight loss interventions reduced systolic and diastolic blood pressure by 4.5 mm Hg and 3.2 mm Hg, respectively. Five out of eight studies reported body weight; weight loss interventions reduced weight by 4.0 kg as compared to controls. No useful information on adverse effects was reported in the included trials. In conclusion, we found no evidence for effects of weight loss diets on death or long-term complications and adverse events. Results on blood pressure and body weight should be considered uncertain, because not all studies were included in the analyses.
We looked for randomised controlled trials in people with recent onset of stroke symptoms that compared LMWH or heparinoids with UFH. We found nine trials involving 3137 participants; overall these trials had a moderate risk of bias (this means that the results are likely to be less credible than if the risk of bias was low). No new trials were included in this updated review. None of the studies reported reliable information on disability or recovery after stroke. Compared with UFH, there was no evidence of an effect of LMWH or heparinoids on death from all causes during the treatment period (quality of the evidence was low). Although LMWH or heparinoid were associated with significantly fewer clots in leg veins (DVT) than UFH, the number of major events such as when a blood clot becomes lodged in an artery in the lung (pulmonary embolism) and bleeding inside the skull (intracranial haemorrhages) was too small to know whether the harms outweighed the benefits. For people with ischaemic stroke who need immediate treatment with anticoagulants, evidence from the included clinical trials did not provide reliable evidence on the balance of risk and benefit for each type of heparin. Additional large scale research would be needed to resolve this uncertainty. Overall, there was a moderate risk of bias in the included studies. Using GRADE criteria we found that evidence quality was low overall.
Results from this systematic review show that ART soon after birth is preferable to delaying treatment, because infants are less likely to die or become sick. Starting a first-line treatment regimen that includes lopinavir/ritonavir rather than nevirapine is preferable, because infants and young children are less likely to have to stop treatment, whether or not they had previously been exposed to nevirapine. However, lopinavir/ritonavir is more expensive than nevirapine. It is also currently only available as an inconvenient liquid, which tastes bitter and has to be refrigerated, making it challenging to implement in all parts of the world. While waiting for better formulations to become available, it may be possible to switch from lopinavir/ritonavir to nevirapine once the HIV virus levels become undetectable. However, based on the evidence currently available, a viral load test would be required to identify those children who could safely substitute lopinavir/ritonavir with nevirapine. Viral loads are expensive and not widely available in most countries in sub-Saharan Africa. An alternative treatment approach is to give a stronger drug combination (four different drugs together) when treatment is first started, then reduce down to three drugs after a short while. However, this strategy did not appear to have long-term benefits. A 'treatment interruption' strategy, in which infants start ART soon after birth but then stop medication after 1-2 years, is difficult to implement. Children stopping ART need to restart it very quickly to prevent them becoming sick, and monitoring a child off treatment is challenging in settings with few resources.
We found 18 studies including a total of 2268 people: 12 included adults, five included children and one included individuals from both age groups. Most people included in the studies had mild to moderate persistent asthma, and studies generally lasted between three and 12 months. People in the intervention group were given one of a variety of technologies to record and share their symptoms (text messaging, Web systems or phone calls) and were compared with a group of people who received usual care, or a control group. We could not tell whether people in the telemonitoring groups had a higher or lower chance than people in the control group of having attacks that would require a course of oral steroids, a visit to the emergency department or a hospital stay. No reports described other potential harms of home telemonitoring. Studies used lots of different types of technology, and we couldn't tell whether some were better than others. Our confidence in the results ranged from moderate to very low, meaning that additional studies are likely to change some of these results and may influence how much we believe them. Using technology to monitor people with asthma from home may offer benefits over usual care for overall quality of life, but the effect was small, and studies did not agree with each other. These interventions may provide benefits for lung function, but lots of people dropped out of the studies, so we couldn't be sure.
We included 29 randomised controlled trials in the review (3227 participants). Of these, results of 18 trials were pooled (2740 participants). Results from the remaining 11 trials could not be used in the meta-analysis because investigators did not use a way of measuring adhesions that would allow findings to be pooled with other data, or because important statistical information was not reported. We searched all evidence up to April 2014. Only one study evaluated pelvic pain and provided no evidence that the adhesion prevention agent made a difference. No evidence suggests that any of the investigated agents affected live birth rate. Regarding adhesions, participants given a fluid agent during surgery were less likely to form adhesions than participants who did not receive a fluid agent. When fluids and gels were compared with each other, gels appeared to perform better than fluids. No pharmacological agents showed good evidence of causing a significant effect on adhesions. No studies looked at differences in quality of life. All studies apart from one stated that investigators were going to assess serious adverse outcomes associated with the agents, and no adverse effects were reported. For gels, results suggest that for a woman with a 77% risk of developing adhesions without treatment, the risk of developing adhesions after a gel is used would be between 26% and 65%. For a woman with an 83% risk of worsening of adhesions after no treatment at initial surgery, the chance when a gel is used would be between 16% and 73%. Similarly, for hydroflotation fluids in a woman with an 84% chance of developing adhesions with no treatment, the risk of developing adhesions when hydroflotation fluid is used would be between 53% and 73%. Fluids and gels appear to be effective in reducing adhesions, but more information is needed to determine whether this affects pelvic pain, live birth rate, quality of life and long-term complications such as bowel obstruction. Further large, high-quality studies should be conducted in which investigators use the standard way of measuring adhesions as developed by the American Fertility Society (the modified AFS score). The quality of the evidence ranged from low to high. The main reasons for downgrading of evidence were imprecision (small sample sizes and wide confidence intervals) and poor reporting of study methods.
We identified 17 studies which compared premedication with a placebo prior to day case surgery. Twelve studies involved benzodiazepines (sedatives), two involved opioids (painkillers), two involved beta-blockers, one compared a benzodiazepine with a beta-blocker and one involved a herbal medication. In general, the studies were of poor quality and many used anaesthetic techniques which are no longer common. Only seven studies directly measured time to ambulation or discharge and found that this was not affected by the use of premedication. Some studies used specific tests to assess for residual effects of the premedication. Although these were often impaired after surgery, this did not appear to delay discharge.
We included 129 studies published up to August 2013 which examined 18,086 people. Participants included men and women of any age, although most were between 18 to 70 years old. There was considerable variation in the reporting quality of the studies. A quarter were partially funded by pharmaceutical companies, and it was unclear what impact this may have had on reporting of the results. Most studies appeared to be conducted within dermatology outpatient clinics. A range of treatments were evaluated, mostly in single studies. Most treatments were applied once or twice daily for between two and four weeks. Mycological cure (disappearance of fungal infection); and clinical cure (absence of symptoms such as redness and itchiness); were assessed in the majority of studies, along with side effects. Less than half of the studies assessed disease recurrence and hardly any assessed the time to achieve clinical cure, or whether study participants considered they had been cured. Almost all treatments were effective at achieving both mycological and clinical cure, compared with placebo. We combined data for several outcomes in two individual treatments: terbinafine against placebo and naftifine against placebo. Both were shown to be effective treatments. We combined data on different groups of treatments. There was no difference in rate of mycological cure between azoles and benzylamines. Combinations of antifungal treatment with a topical corticosteroid achieved higher clinical cure rates, probably because the skin redness disappears sooner due to the effect of the corticosteroid. There was no evidence of any difference in the speed of resolution of fungal infection with these combination treatments. The overall quality of the evidence for the different outcomes was rated as low to very low. There is currently insufficient evidence to be able to decide if one particular treatment is better than any of the others. All the treatments we evaluated reported low rates of mild side effects. This review highlights the need for better quality studies on treatments for fungal skin infections. Despite the limitations of our main findings, it appears that most active treatments are effective and further research should concentrate on comparing active treatments, rather than comparisons with a placebo. Topical treatments that need to be used only once a day over a short period of time may be more appealing in practice. Some of the treatments examined in our review may not be readily available in-low income countries.
This review looked at the effect of cutting down the proportion of energy from fat in our food on body weight and fatness in both adults and children who are not aiming to lose weight. The review found that cutting down on the proportion of fat in our food leads to a small but noticeable decrease in body weight, body mass index and waist circumference. This effect was found both in adults and children. The effect did not change over time.
This review looked at studies of iodised salt in the diet that included a comparison group. Six studies, most of them in children but some also in adults, were included. Iodine in the urine increased in all but one studies, but there was some concern that small children did not eat enough salt to achieve adequate iodine status. Some studies, but not all, also showed a reduction in the enlargement of the thyroid gland (goitre) that can accompany lack of iodine in the diet. Adverse effects were not reported, but these may not have been studied adequately. More high quality long term studies measuring outcomes related to child development, to deaths associated with iodine-deficiency and to adverse effects are needed.
We found 26 studies including a total of 7654 adults with cancer. Most studies included both males and females. With regard to cancer type, most studies included people with a specific type of cancer, but some included a variety of cancer types. Furthermore, the type of screening differed: half of the studies asked participants to self-complete a screening questionnaire about their psychosocial health, while in the remaining studies screening interviews were conducted in which a healthcare professional questioned participants about their well-being face-to-face. Several studies showed benefits of screening on psychosocial well-being of cancer patients, such as their health-related quality of life, distress, care needs, and patient satisfaction. However, some studies also found negative effects. There were important differences between the studies: they assessed different psychosocial aspects (e.g. health-related quality of life, distress, care needs, and patient satisfaction) and differed in their modes of screening (i.e. self-report screening questionnaire versus screening interview), timing and frequency of the screening (1 to 12 times), outcome measures, and outcome time points. Due to these differences, only three studies studying the same intervention could be included in the analysis. Our results do not support the screening of psychosocial well-being and care needs in people with cancer. The certainty of the evidence was low, which means that we are uncertain about the results of the review due to variations in characteristics, and results of the studies and study designs.
This review identified eleven randomised controlled trials that compared antidepressants with a placebo in people with schizophrenia who also had depression. There was some evidence that antidepressants did lead to an improvement in global outcome, but the small number of studies providing usable data and their poor quality, suggest that this evidence should be interpreted with caution. At present, there is no convincing evidence either to support or refute the use of antidepressants in treating depression in people with schizophrenia. Further well-designed, conducted and reported research is needed in this area.
We included six randomised controlled trials that enrolled a total of 561 people. The trials were conducted in Germany (three trials), Iran, India, and China. In people with high-risk keratoplasty, one study compared systemic MMF with placebo, one study compared systemic MMF with systemic CsA, and one study compared CsA eye drops versus placebo. In people with normal-risk keratoplasty, one study compared tacrolimus eye drops to steroid eye drops, and two studies compared CsA eye drops to placebo in people experiencing rejection after keratoplasty. All studies reported clear graft survival, incidence of graft rejection, and adverse effects. We are uncertain as to the effects of immunosuppressants in the prevention of graft failure and rejection after high- and normal-risk keratoplasty, as the number of trials is limited, and, in general, the trials are small and at risk of bias. Future trials should be large enough to detect important clinical effects, conducted with a view to minimising the risk of bias, and they should measure outcomes important to patients. Three of the studies were supported by the pharmaceutical industry. We judged the quality of the evidence to be low to moderate. There was risk of bias in the included studies; the results were sometimes imprecise because of the small number of studies and small number of people enrolled in these studies; and in some analyses the results of individual trials were inconsistent.
The reviewers identified 10 trials assessing the effect of tamoxifen on survival, quality of life, tumour size, and treatment side effects in advanced hepatocellular carcinoma. Tamoxifen had no significant effect on survival or tumour size. Tamoxifen did not improve quality of life.
This review found 69 studies that evaluated educational outreach visits. Educational outreach visits appear to improve the care delivered to patients. When trying to change how health care professionals prescribe medications, outreach visits consistently provide small changes in prescribing, which might be potentially important when hundreds of patients are affected. For other types of professional practice, such as providing screening tests, outreach visits provide small to moderate changes in practice. But the effects really varied and why it varied could not be explained.
Women who received chemotherapy after surgery (starting within eight weeks of surgery) survived approximately 25% longer than those receiving radiotherapy after surgery. Assuming that 60% of women with stage III endometrial cancer usually survive at least five years after surgery and radiotherapy, this would increase to 75% if they receive surgery and chemotherapy instead, depending on other risk factors, such as age. The risk of death which might have been caused by treatment was low with both chemotherapy and radiotherapy but we could not be sure if one was more harmful than the other. Chemotherapy may be associated with more side-effects (low blood counts, nerve damage and hair loss) compared with radiotherapy. In the trial that compared two different chemotherapy treatments, there was no clear evidence that using three anti-cancer drugs was better than using two. However, the final overall survival results of this trial have not yet been reported. Severe side-effects were much more common in women treated with three anti-cancer drugs than two drugs. Chemotherapy appears to be more effective than radiotherapy after surgery for women with stage III and IV endometrial cancer but may cause more side-effects. More research is needed to determine whether the addition of radiotherapy to chemotherapy improves outcomes and which anti-cancer drugs are best.
In this review we included two randomised trials comparing planned caesarean versus planned vaginal birth for twin pregnancies which together included 2864 women. For important outcomes the evidence was assessed as being of moderate quality. For maternal mortality no events were reported in one trial and two deaths (one in each group) in the other. There was no clear evidence of differences between women randomised to planned caesarean or planned vaginal birth for death or serous illness in either the mothers or babies. No studies reported childhood disability. The number of women undergoing caesarean section was reported in both trials. Most women in the planned caesarean group had treatment as planned (90.9%), whereas in the planned vaginal birth group 42.9% had caesarean section for at least one twin. There were no significant differences between groups for failure to breastfeed or for postnatal depression. There is very little clear research evidence to provide guidance on the method of birth for twin pregnancies. The benefits and risks should be made available to women, including short-term and long-term consequences for both mother and babies. Future research should aim to provide more clarity on this issue as medical interventions in the birth process should be avoided unless there is reasonable clinical certainty that they will be of long-term benefit.
In this review of randomised controlled studies, we evaluated the effects of adding marine omega-3 fatty acids to women’s diets during pregnancy or lactation on allergic diseases in their children. We analysed eight trials that involved 3366 women and 3175 children. The women were randomly assigned to receive a marine omega-3 supplement (as fish oil capsules, or added to foods) or no treatment during pregnancy (five trials), during breast feeding (two trials) or both pregnancy and breast feeding (one trial). Overall, the methodological quality of the trials varied, with only two trials being at low risk of bias. Overall, the results showed little effect of maternal marine omega-3 supplementation during pregnancy and/or breast feeding for the reduction of allergic disease in the children. However there were reductions in some outcomes such as food allergy during the baby's first year and eczema with marine omega-3 supplementation in women with a baby at high risk of allergy. Currently, there is not enough evidence to say that omega-3 supplements from marine origin during pregnancy and/or breast feeding for mothers will reduce allergies in their children. In terms of safety for the mother and child, omega-3 fatty acids supplementation from marine origin during pregnancy did not show increased risk of excessive bleeding after the baby was born (postpartum haemorrhage) or early childhood infections.
The last search for trials was in February 2018. We assessed the evidence from 14 randomised controlled trials comparing lamotrigine with carbamazepine. We were able to combine information for 2572 people from nine of the 14 trials; for the remaining 1215 people from five trials, information was not available to use in this review. Results The results of the review suggest that people are more likely to withdraw earlier from carbamazepine than lamotrigine treatment. The most common medicine-related reason for withdrawal was side effects: 52% of total withdrawals in participants on carbamazepine and 36% of total withdrawals in participants on lamotrigine. The second most common medicine-related cause for withdrawal was seizure recurrence: 58 of 719 total withdrawals (8%) on carbamazepine and 105 of 697 total withdrawals (15%) on lamotrigine. The results suggest that recurrence of seizures after starting treatment with lamotrigine may happen earlier than treatment with carbamazepine. They also suggest that freedom from seizures for a period of six months may occur earlier on carbamazepine than lamotrigine. The majority of the people included in the 14 trials (88%) experienced focal seizures, so the results of this review apply mainly to people with this seizure type. The most common side effects reported by participants during the trials were dizziness, fatigue, gastrointestinal problems, headaches and skin problems. These side effects were reported a similar number of times by people taking lamotrigine or carbamazepine. Quality of the evidence For people with focal onset seizures, we judged the quality of the evidence to be high for the outcomes of seizure recurrence and remission of seizures and we judged the quality of the evidence to be moderate for the outcome of treatment failure. The design of the trials (specifically, whether the people and treating clinicians knew which medication they were taking) may have influenced the rates of withdrawal from treatments. Up to 50% of people in the trials used in our results may have been wrongly classified as having generalised seizures; for people with generalised onset seizures, we judged the quality of the evidence to be moderate for the outcomes of seizure recurrence and remission of seizures and low quality for the outcome of treatment failure. Conclusions For people with focal onset seizures, lamotrigine and carbamazepine are effective treatments and a choice between these two treatments must be made carefully. More information is needed for people with generalised onset seizures. We recommend that all future trials comparing these medications, or any other antiepileptic medications, should be designed using high-quality methods. Seizure types of people included in trials should also be classified very carefully to ensure that the results are also of high quality.
In most cases, efforts to regulate health worker migration have not been properly evaluated. The review authors found only one study that met their stated requirements for types of study designs. This study looked at the impact of United States (US) immigration law on the number of nurses emigrating from the Philippines to the USA. US government immigration laws were changed in the 1960s, giving equal access to European and non-European immigrants. The study measured the number of nurses migrating from the Philippines to the USA in the years before and after the law had changed. The study showed that: - The change in US immigration laws probably increased the number of nurses migrating from the Philippines to the USA. The quality of this evidence is moderate. The review shows that there is a huge gap in our knowledge about the effectiveness of policy interventions that attempt to regulate the movement of health professionals from low- and middle-income countries.
Randomised trials have compared transjugular intrahepatic portosystemic stent-shunts with paracentesis. Mortality, gastrointestinal bleeding, renal failure, or infection did not differ significantly between the two intervention groups. Transjugular intrahepatic portosystemic stent-shunts effectively decreased the risk of ascites fluid re-accumulation, but was associated with an increased risk of hepatic encephalopathy.
This review identified four studies that compared these drugs with placebo. Over the first 2 hours of treatment there was no evidence that patients improved in terms of lung function, although a possible late benefit was detected. The studies do not give a clear indication of whether there was benefit in terms of reduced symptoms or hospital admissions, but side effects were found to be more common with methylxanthines. We conclude that, given current evidence, methylxanthines should not be used for acute exacerbations of chronic obstructive pulmonary disease.
We included one study (enrolling 70 newborn infants) that compared needle aspiration followed by immediate removal to chest tube placement for the treatment of pneumothorax and one study (72 newborn infants) that compared needle aspiration with the angiocatheter left in situ to chest tube placement for the treatment of pneumothorax. Evidence is up to date as of June 2018. The use of needle aspiration compared to chest tube placement did not reduce mortality or any complications related to the procedure. About 30% of the infants with pneumothorax who were treated with needle aspiration followed by immediate removal never required the placement of an intercostal tube; none of the infants with pneumothorax who were treated with needle aspiration left in situ required the placement of an intercostal tube. However multiple factors might explain this finding. The two small trials identified do not provide sufficient information to determine which of the two techniques is better to treat pneumothorax in neonates. However it seems that needle aspiration might reduce the need for an intercostal tube in a relevant proportion of newborn infants.
Eight of the trials looked at email compared with standard methods of communication. Where email was compared to standard methods of communication we found that we could not properly determine what effect email was having on patient/caregiver outcomes, as there were missing data and the results of the different studies varied. For health service use outcomes the situation was the same, but some results seemed to show that an email intervention may lead to an increased number of emails and telephone calls being received by healthcare professionals. One of the trials looked at email counselling compared with telephone counselling. We found that it only looked at patient outcomes, and found few differences between groups. Where there were differences these showed that telephone counselling leads to greater changes in lifestyle than email counselling. None of the trials measured how email affects healthcare professionals and only one measured whether email can cause harm. All of the trials were biased in some way and when we measured the quality of all of the results we found them to be of low or very low quality. As a result the results of this review should be viewed with caution. The nature of the results means that we cannot make any recommendations for how email might best be used in clinical practice. Future research should make allowances for how quickly technology changes, and should consider how much email would cost to introduce and what effect it has on the use of healthcare resources. Research reports should be sure to clearly report their methods and findings, and researchers interested in carrying out research in this area should be assisted in developing ideas and put them into action.
We included five small trials that randomised only 234 people, almost all with stroke. Two trials investigated dysarthria treatment versus an attention control and three compared one treatment with usual care. There were no trials that compared one treatment to no treatment. We found few randomised controlled trials of dysarthria treatment, and those that have been conducted involved small numbers of participants, or were not adequately designed or had serious reporting flaws. We compared many different measures at various time points after treatment, so caution is recommended when interpreting results. We found no evidence of effectiveness on most measures, including long-lasting improvement in every day communication abilities. A positive finding was short-term improvement in muscle movement, such as tongue and lip control. However, this result is not reliable because it was based on small numbers of people, and we found concerns about the conduct and reporting of some trials. This finding needs to be investigated in a bigger, better designed trial. We found insufficient evidence to tell us whether any one treatment is better than any other or whether treatment is better than general support, or no treatment. We found no studies that examined timing, duration, or intensity of treatment. This is a clinically important question and should be considered in future trials. The included trials varied in quality but all included small numbers of participants. Overall, studies were rated as low to very low quality evidence.
This review assesses the various forms of medication used to treat the condition. Nineteen randomised controlled trials were included (3382 participants). Most were of low quality. The findings of the review may not be wholly relevant to primary care as most of the trials were conducted in a hospital setting and over half involved ear cleaning as part of the treatment (this is generally not available in primary care). However, the review does demonstrate that topical treatments alone are effective at treating acute otitis externa. There was little to choose between them in terms of effectiveness. However, when treatment needs to be extended beyond one week acetic acid drops appear to be less effective than antibiotic/steroid drops. In addition, symptoms persist for two days longer in those treated with acetic acid. More research is needed to determine the effectiveness of steroid-only drops. Patients treated with antibiotic/steroid drops can expect their symptoms to last for approximately six days after treatment has begun.
A total of seven randomized controlled studies met the inclusion criteria and enrolled a total of 606 participants. Because of differences in the way that the studies were designed, we were unable to combine their reported results. The results from individual studies that compared heparin at a dose of 1 to 2 IU/mL under continuous pressure were imprecise and do not provide definitive evidence of a difference. The effective dose of heparin has not yet been determined. This evidence needs to be confirmed in future trials. All studies had a moderate to high risk of methodological bias. The review of trials therefore revealed that more research is needed to determine exactly how long an arterial catheter maintained with a normal saline flush solution can be in place and remain functional (to accurately measure blood pressure and pulse and to provide blood samples that can be used to monitor oxygenation and other variables).
We included nine randomised controlled trials (20,101 employees) and nine cohort studies (1280 employees) that examined the effects of training and the use of assistive devices on preventing low-back pain and reducing back-related disability. We found no studies that examined the effects of training or the use of assistive devices as part of a treatment plan for back pain. We found moderate quality evidence that reports of back pain, back-related disability or absence from work were similar between groups who received training on proper lifting techniques and assistive devices compared to a control group that received either no training, minor advice only, professional education, exercise training or back belts. Reports of back pain were also similar between those who received intensive training and those who received shorter instruction. These findings were consistent when measured in the short-term or long-term and when examined in randomised trials or cohort studies. These results are similar to other reviews that examined a range of possible prevention measures. Some of the other reviews found that workers who received training were satisfied and demonstrated increased knowledge on the subject, but this did not appear to consistently translate into behaviour change. In conclusion, training workers in proper material handling techniques or providing them with assistive devices are not effective interventions by themselves in preventing back pain. Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
We found a total of five randomised clinical trials (involving 1466 women). In three of the trials (involving 1268 women), oral methylergometrine was compared with placebo (two trials) or the Japanese traditional herbal medicine Kyuki-chouketsu-in (one trial). The other two trials (involving 198 women) did not report information on relevant outcomes of interest for this review. Overall, there was no clear evidence that prophylactic oral methylergometrine was effective in reducing haemorrhage after childbirth. The trials were not of good quality and adverse events were not well-reported. We did not find any completed trials looking at the effectiveness of homeopathic remedies in reducing haemorrhage after childbirth. The effectiveness of such remedies warrants further investigation.
The benefits and risks of multiple-micronutrient supplementation during lactation are not clear from randomised controlled studies. Key vitamins and minerals, particularly iodine, iron and zinc, are required in small amounts to ensure normal body metabolism, physical growth and development. Nutrient deficiency affects nearly one third of the world’s population, especially in low- and middle-income countries. Breastfeeding mothers need higher levels than usual in order to provide sufficient vitamins and minerals for their own health and that of their babies, particularly for normal functioning and the growth and development of the baby. Previous studies have assessed supplementation of individual micronutrients. This review looked at the use of multiple-micronutrient supplements for breastfeeding women for improving outcomes for the mother and her baby. We searched for studies on 30 September 2015 and identified two small studies (involving 52 women) for inclusion in this review. The studies were carried out in Brazil and the USA and included women who had a low socioeconomic status. The studies were poorly reported and this lack of information made it difficult to determine whether the studies were at risk of bias. Neither of the studies provided data for any of this review's important outcomes: maternal illness (fever, respiratory infection, diarrhoea), adverse effects of micronutrients within three days of taking them, infant death (defined as a child dying before reaching one year of age). Similarly, there were no data for any of the other outcomes that we were interested in. For the mother, these outcomes were maternal anaemia, and women's satisfaction. For the baby, these outcomes were micronutrient deficiency; illness episodes (fever, respiratory infection, diarrhoea, other), adverse effects of micronutrients within three days of the woman receiving the supplement. However, one of the included studies reported that multiple-micronutrient supplementation was effective for lactating women recuperating from anaemia. There is a need for high-quality studies to assess the effectiveness and safety of multiple-micronutrient supplementation for breastfeeding women for improving outcomes for the mother and her baby. Larger studies with longer-term follow-up would improve the quality of studies and provide stronger evidence. Further research should focus on whether multiple-micronutrient supplementation during lactation (compared with no supplementation, a placebo or supplementation with fewer than two micronutrients) is beneficial to the mother and her baby and any associated adverse effects of the intervention. Futher studies should report on important outcomes such as those listed in this review and consider the risks of excess supplementation. Future studies could more precisely assess a variety of multiple-micronutrient combinations and different dosages and look at how these effect outcomes for the mother and her baby.
This summary of a Cochrane review of 22 studies with 8275 participants (search update: 15 August 2012) presents what we know from research about the effect of opioids on osteoarthritis (OA). We searched scientific databases for clinical trials looking at pain, function, safety, and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis. The review shows that in people with osteoarthritis: - Opioids have a small effect on pain or physical function. - Opioids probably cause side effects. However, we do not have precise information about rare but serious side effects. What is osteoarthritis and what are opioids? OA is a disease of the joints, such as your knee or hip. When the joint loses cartilage, the bone grows to try to repair the damage. Instead of making things better, however, the bone grows abnormally and makes things worse. For example, the bone can become misshapen and make the joint painful and unstable. This can affect your physical function or ability to use your knee. Opioids are generally conceived as powerful pain-relieving substances that are used for the pain of cancer or osteoarthritis. Some examples of opioids are codeine-containing Tylenol® (1, 2, 3, and 4), hydromorphone (Dilaudid), oxycodone (Percocet, Percodan), morphine, and others. They can be taken in a pill form, as an injection, or as a patch placed on the painful area. Best estimate of what happens to people with osteoarthritis who take opioids Pain - People who took opioids rated improvement in their pain to be about 3 points on a scale of 0 (no pain) to 10 (extreme pain) after one month. - People who took a placebo rated improvement in their pain to be about 2 points on a scale of 0 (no pain) to 10 (extreme pain) after one month. Another way of saying this is: - 41 people out of 100 who used opioids responded to treatment (41%). - 31 people out of 100 who used placebo responded to treatment (31%). - 10 more people responded to treatment with opioids than with placebo (difference of 10%). (High-quality evidence) Physical function - People who took opioids rated improvement in their physical function to be about 2 points on a scale of 0 (no disability) to 10 (extreme disability) after one month. - People who took a placebo rated improvement in their physical function to be about 1 point on a scale of 0 (no disability) to 10 (extreme disability) after one month. Another way of saying this is: - 34 people out of 100 who used opioids responded to treatment (34%). - 26 people out of 100 who used placebo responded to treatment (26%). - 8 more people responded to treatment with opioids than with placebo (difference of 8%). (High-quality evidence) Side effects - 22 people out of 100 who used opioids experienced side effects (22%). - 15 people out of 100 who used a placebo experienced side effects (15%). - 7 more people experienced side effects with opioids than with placebo (difference of 7%). (Moderate-quality evidence) Drop-outs because of side effects - 64 people out of 1000 who used opioids dropped out because of side effects (6.4%). - 17 people out of 1000 who used a placebo dropped out because of side effects (1.7%). - 47 more people dropped out because of side effects with opioids than with placebo (difference of 4.7%). (High-quality evidence) Side effects resulting in hospitalisation, persistent disability, or death - 13 people out of 1000 who used opioids experienced side effects resulting in hospitalisation, persistent disability, or death (1.3%). - 4 people out of 1000 who used a placebo experienced side effects resulting in hospitalisation, persistent disability, or deaths (0.4%). - 9 more people experienced side effects resulting in hospitalisation, persistent disability, or death with opioids than with placebo (difference of 0.9%). (Low-quality evidence) Withdrawal symptoms - 24 people out of 1000 who used opioids experienced withdrawal symptoms (2.4%). - 9 people out of 1000 who used a placebo experienced withdrawal symptoms (0.9%). - 15 more people experienced withdrawal symptoms with opioids than with placebo (difference of 1.5%). (Moderate-quality evidence)
Six randomised clinical trials with a total of 710 patients were included in this systematic review. The trials were generally with high risk of bias. We could not demonstrate any significant effect of propylthiouracil on all-cause mortality, liver-related mortality, liver complications, or liver histology of patients with alcoholic liver disease. Although propylthiouracil was not associated with a significant increased risk of non-serious adverse events, there were occasional instances of serious adverse events (leukopenia, generalized bullous eruption). The trials included a small number of patients, and so, the risk of random error (error due to play of chance) is high. There seems to be no evidence for using propylthiouracil for alcoholic liver disease outside randomised clinical trials.
We searched for available research up to January 2016 and found 260 studies with different designs. We included a number of non-randomised designs (where investigators did not assign participants to a certain treatment): – 7 comparative cohort studies (a group of people followed over time; six studies compared 968 patients who were taking methylphenidate to 166 controls who were not taking methylphenidate; and 1 study included 1224 patients that were taking or not taking methylphenidate during different time periods); – 4 patient-control studies (comparing two groups of people: 53,192 were taking methylphenidate, and 19,906 were not); – 177 non-comparative cohort studies (2,207,751 participants) with no control group (i.e. who were not taking methylphenidate); – 2 cross-sectional studies (96 participants were taking methylphenidate at a single time point); and – 70 patient reports/series (206 participants were taking methylphenidate). We also included methylphenidate groups from randomised clinical trials (RCTs; experiments in which participants are randomly put into independent groups that compare different treatments). All RCTs assessed methylphenidate versus other interventions for ADHD and follow-up periods from RCTs. We only used the data from the intervention arm with methylphenidate. In all the included non-comparative cohort studies, 2,207,751 participants were taking methylphenidate. Participants' ages ranged from 3 years to 20 years. The findings suggest that methylphenidate administration might lead to serious adverse (harmful) events, including death, cardiac problems, and psychotic disorders. About 1 in 100 patients treated with methylphenidate seemed to suffer a serious adverse event. Withdrawal from methylphenidate due to serious adverse events occurred in about 1.2 out of 100 patients treated with methylphenidate. Withdrawal from methylphenidate due to any adverse events occurred in about 7.3 out of 100 patients treated with methylphenidate. We also noted a large proportion of non-serious adverse events. More than half the patients exposed to methylphenidate seemed to suffer one or more adverse events. Withdrawal from methylphenidate due to non-serious adverse events occurred in about 6.2 out of 100 patients exposed to methylphenidate. Withdrawal of methylphenidate for unknown reasons was 16.2 out of 100 patients exposed to methylphenidate. The quality of the evidence and hence the certainty or reliability of the evidence for the comparative studies is very low. The reliability of the evidence for the non-comparative studies is low due to weaknesses in study design. Accordingly, it is not possible to accurately estimate the risks of adverse events in children and adolescents prescribed methylphenidate. Methyphenidiate might be associated with a number of serious adverse events. Methylphenidate produces a large number of other non-serious harmful effects in children and adolescents with ADHD. We suggest that clinicians and parents are alert to the importance of monitoring adverse events in a systematic, meticulous manner. If methylphenidate is to continue to have a place in ADHD treatment in the future, we need to identify subgroups of patients in whom the benefits of methylphenidate outweigh the harms. Just as we need to be able to identify who is likely to benefit from treatment, we also need to be able to identify those who are most at risk of experiencing adverse events. In order to do this, we need to undertake large-scale, high-quality RCTs along with other studies aimed at identifying those who respond and those who do not respond to treatment.
One study found that all patients improved during the study period, but the treatment effect did not differ between the group who received rTMS and the group who received sham rTMS. The other study administered more sessions and reported higher levels of improvement of panic symptoms in those people who received rTMS compared to those who received sham rTMS. Although neither trial reported any serious side effects, they provided only very low quality evidence for adverse event outcomes. On the basis of the limited quality of the evidence available we were unable to determine how safe rTMS is. The limited information available from these two studies is insufficient to conclude whether rTMS is effective in reducing the severity of panic disorder symptoms. The main limitation of this review was that the number of people with panic disorder who were involved was too small. To find out more about rTMS for panic disorder, there is a need for more studies to be carried out which involve larger numbers of people and compare sham rTMS with real rTMS.
We included 21 randomised clinical trials in this review. All trials had high risk of bias ('systematic error'). A total of 2348 people were randomised either to somatostatin analogues or a control in the 21 trials. The overall number of people with postoperative complications was lower by 30% in the somatostatin analogues group but there was no difference in postoperative mortality, re-operation rate or overall length of hospital stay between the groups. Pancreatic fistula is drainage of pancreatic juice secreted by the remaining pancreas to the exterior. This was lower in the intervention group by 34%. The proportion of these fistulas that resulted in change to the treatment given to the participants is not clear. When we included trials that clearly distinguished fistulas that required change to the treatment given to the participants, there was no difference between the two groups. Participant quality of life was not reported in any of the trials. In conclusion, somatostatin analogues reduce the incidence of pancreatic fistula. Further trials with sufficient participant numbers and a low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection.
The included studies are not easily comparable because of differences in the treatment being studied, the dosage of these treatments, the length of study (and other differences in the study methods), and differences in the types of participants included for the research. The studies were generally well designed in order to reduce the possibility of bias, although for most studies the methods describing how participants were randomised were not described in detail. Otherwise, the risk of bias was low for most studies in the other categories. Serious side effects of treatment were uncommon, except for nerve damage in a long-term trial of dichloroacetate in adults. One trial studied high-dose coenzyme Q10 treatment. This treatment had no clinical benefit. Three trials used creatine monohydrate: one trial reported improved muscle strength and biochemical measurements, but the other two trials reported no benefit (total of 38 participants). One trial studied the effects of a combination of coenzyme Q10, creatine monohydrate and lipoic acid, and reported a statistically significant improvement in biochemical measurements and ankle strength, but no clinical improvement (16 participants). Five trials studied the effects of dichloroacetate: three trials in children showed a statistically significant improvement in biochemical measurements but no clinical benefit on physiological measurements and exercise tests (total 63 participants); one trial of short-term therapy in adults demonstrated no clinical improvement in physiological measurements (total eight participants), and one longer-term trial in adults was terminated prematurely due to adverse effects without clinical benefit (using a combined scale of treatment effect, in 30 participants). One trial using dimethylglycine showed no significant effect on biochemical markers in five participants. One trial using a whey-based supplement demonstrated statistically significant improvement in biochemical markers but no clinical benefit in muscle strength or on health questionnaires (13 participants). Further randomised controlled trials of high quality are needed. They should strictly address outcomes which are relevant to patient care and quality of life, and study these in particular subtypes of mitochondrial disease at a time. The current repertoire of nutritional supplements have been not shown to be effective and future trials should study new treatments.
We identified two trials with 156 participants for this review. The comparisons included in these two trials were 1) percutaneous cholecystostomy plus laparoscopic cholecystectomy (key hole removal of gallbladder) immediately after the general condition improves (percutaneous cholecystostomy followed by early laparoscopic cholecystectomy) versus planned delayed laparoscopic cholecystectomy performed routinely (1 trial; 70 participants) and 2) percutaneous cholecystostomy versus conservative treatment (supportive treatment and antibiotic treatment) (1 trial; 86 participants). Both trials were at high risk of systematic error (prone to arrive at wrong conclusions because of the way the trials were designed and data were analysed). There was no significant difference in the proportion of participants who died or developed complications between any of the comparison groups. Quality of life was not reported in any of the trials. There was no significant difference in the proportion of participants requiring conversion to open cholecystectomy in the only comparison that reported this outcome (percutaneous cholecystostomy followed by early laparoscopic cholecystectomy versus delayed laparoscopic cholecystectomy). The mean total hospital stay and mean costs were significantly lower in the percutaneous cholecystostomy followed by early laparoscopic cholecystectomy group compared with the delayed laparoscopic cholecystectomy group. Because of the few trials included in this review and due to their low sample size, there is risk of random errors (play of chance). Based on the current available evidence, we are unable to determine the role of percutaneous cholecystostomy in the clinical management of high-risk surgical patients with acute cholecystitis. There is a need for well-designed clinical trials with low risk of systematic error and random errors on this issue.
In the present review we assessed the evidence for the efficacy, acceptability and tolerability of citalopram in comparison with all other antidepressants in the acute-phase treatment of major depression. Thirty-seven randomised controlled trials (more than 6000 participants) were included in the present review. In terms of efficacy, citalopram was more efficacious than other reference compounds like paroxetine or reboxetine, but worse than escitalopram. In terms of side effects, citalopram was more acceptable than older antidepressants, like tricyclics. Based on these findings, we conclude that clinicians should focus on practical or clinically relevant considerations including differences in efficacy and side-effect profiles.
We searched scientific sources to identify eligible trials and found 15 studies with 755 patients. The evidence is up to date to April 2015. Fourteen studies compared prophylactic FFP against no FFP and one study compared two types of FFP, both used therapeutically. No studies reported on all outcomes. There was either high risk of bias, or unclear risk, in the majority of trials included in this review. Our primary outcome was death within 30 days after surgery. Six trials (with 287 patients) looked at this outcome and found no clear difference in mortality between the treatment arms but the quality of the evidence was very low. There was also no difference in the amount of blood lost in the first 24 hours following surgery (measured in five trials; low quality evidence), or the risk of returning to theatre for a reoperation (measured in eight trials; moderate quality evidence). Patients who had FFP received significantly more red blood cells, suggesting that FFP may not be effective in this setting (moderate quality evidence). Measurement of a blood test used to assess blood clotting (prothrombin time) was reported in eight trials and showed that clotting was improved by the use of prophylactic FFP (moderate quality evidence). However, the difference was too small to make a difference in clinical practice. Only one included study reported adverse events as an outcome and reported no adverse events due to FFP transfusion. The review found no evidence for the efficacy of FFP for the prevention of bleeding in heart surgery and it found some evidence of an increased overall need for red cell transfusion in those treated with FFP. There were no reported adverse events due to FFP transfusion. Overall the evidence for the safety and efficacy of prophylactic FFP for cardiac surgery is insufficient. The trials focused on prevention of bleeding and did not address prevention of bleeding for patients with abnormal blood clotting or for the treatment of bleeding patients.
The five studies that were included in the review were published between 1995 and 2009 and involved a total of 2277 participants. Four countries were represented (two studies from France and one each from Italy, Sweden, and the Czech Republic). One study involved children and the remaining four trials included only adults. Four of the studies included cancer patients and one included patients in an intensive care unit. We classified the time intervals between dressing changes as short (2 - 5 days) in the more frequently changed dressings group and long (5-15 days) in the less frequently changed group. All studies used transparent dressings made of synthetic materials and two studies used gauze (a fabric dressing that does not stick to the skin) secured with tape when skin was damaged. CVAD dressings were monitored on a daily basis in all trials and participants were followed up at least until the CVAD was removed or until discharge. In one study, the manufacturer provided one of the products, but had no influence in the design or how the results were analysed and reported. The current evidence leaves us uncertain whether the frequency of dressing changes for CVADs influences risk of CRBSI or death. Of particular interest to patients are problems that may be associated with the dressing themselves, such as pain when they are removed and the skin damage that the dressing may cause. We found no clear evidence that pain, which was assessed daily, was affected by the frequency of dressing changes. The quality of the evidence was very low or low. We downgraded quality because of small and few studies, poor study designs and differences in results between the studies. Better designed studies are still needed to show whether longer interval or shorter intervals between dressing changes are more effective in preventing catheter related infections, mortality, skin damage, dressing removal pain, quality of life and cost. This plain language summary is up-to-date as of 10 June 2015.
We included 21 randomised controlled trials involving 1197 participants in this review. The trials were mostly at moderate to high risk of bias. Compared with placebo, UDCA showed improvement in itching in five trials (228 women), no benefit was observed in one trial (16 women) and one trial reported improvement only in women with severe disease (94 women). Distress in the unborn baby or symptoms of asphyxia were reported in five trials (304 women) and although there were fewer instances of fetal distress in the UDCA groups compared with placebo, the difference was not significant. The results from the four trials comparing SAMe and placebo were conflicting. Two trials (48 women) reported better pruritus scores for SAMe compared with placebo and two trials (34 women) reported no significant differences between groups for the disappearance of their pruritus. Comparisons of guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction, Danxioling or Yiganling (used in Chinese medicine for their liver-protective properties) with placebo or one with another was based on data from one trial. Further trials are required before any firm conclusions might be made about their effectiveness. One trial (63 women) compared early delivery versus expectant management. There were no stillbirths or neonatal deaths in either group. No significant differences in caesarean section, passage of meconium-stained liquor or admission to neonatal intensive care unit were observed.
There are a range of treatment options for urticaria, of which the most well-known are the H1-antihistamines. This review evaluated the efficacy and safety of a similar category, the H2-antihistamines, and included 4 low-quality studies, which examined 144 participants. No firm conclusions could be drawn, but the combination of ranitidine with diphenhydramine appeared to be slightly more effective in reducing the symptoms of urticaria than diphenhydramine alone. In one study, cimetidine appeared to be as effective as diphenhydramine. However, the combination of both drugs was more effective than diphenhydramine alone. Drowsiness and sedation were reported with diphenhydramine, but there was no significant difference in the level of sedation with either famotidine or diphenhydramine. The studies were rather old and considered very few outcomes that were of importance to people with urticaria. Therefore, there is currently insufficient evidence to indicate whether this type of medication is effective or not.
We reviewed studies that compared these two highly effective methods and found the IUD to be better at preventing pregnancy than depot medroxyprogesterone acetate (DMPA). Relevant to HIV positive women are the results of one small trial that found that women using the IUD for contraception where less likely to experience a worsening of their HIV disease than those using hormonal contraception. A large, high quality study is urgently needed to shed light on these findings.
We searched for and summarized all the randomized controlled trials that looked at using these drugs to treat bleeding or pain related to an IUD. We also included trials that studied the use of these drugs to prevent these problems. We found 15 trials from 10 countries, with more than 2700 women studied. These drugs reduced both bleeding and pain with intrauterine device use. Whether one drug is better than another was not clear. Similarly, the best dosing was not clear. Preventive treatment with these drugs around the time of IUD insertion had mixed results. No serious problems were reported, but stomach upset and sleepiness can occur with this class of drugs. Because of their safety, low cost, and wide availability, these drugs are appropriate treatment for women who have troublesome bleeding or pain with IUD use.
We identified 10 randomized controlled trials (studies where participants are randomly allocated to either an experimental or a control group) involving 1458 participants up to December 2018. Seven of the trials (1285 participants) provided findings on the number of deaths, serious adverse events, and lung injuries in the three months following oxygen therapy in the ICU. Lung injury was measured according to participants developing acute respiratory distress syndrome or pneumonia. Five trials included adults admitted to an ICU caring for patients with a range of serious health conditions and one to a surgical ICU. Two trials involved adults with traumatic brain injury; one trial adults after cardiac arrest and resuscitation; and one trial adults with stroke. All participants in six trials received invasive mechanical ventilation directly through a tube into the main airway. In one trial some of the participants were on mechanical ventilation, whilst others received non-invasive oxygen administration. Three trials involved adults receiving non-invasive oxygen. All trials compared more with less oxygen, however using very different levels of oxygen supplementation. Oxygen therapy was given for timeframes ranging from one hour to the length of hospital admission. We are uncertain about the effects of higher levels of oxygen as our findings are based on very low-certainty evidence. We found no evidence for a beneficial effect of higher compared with lower supplemental oxygen levels for adults admitted to ICU. Higher levels of oxygen may have increased the risk of death (4 trials; 1135 participants) and serious adverse events (6 trials; 1234 participants). There was no evidence of a difference in lung injuries with the use of higher supplemental oxygen compared with lower supplemental oxygen, but the evidence is very uncertain (5 trials; 1167 participants). None of the included trials reported on quality of life at any time point, acute myocardial infarction, and stroke. Only one trial reported on sepsis. The numbers of participants enrolled in the trials were too small to permit a definitive judgement about the review findings. The trials varied in the types of illness of the participants, their associated clinical care, disease severity, the targets for how much oxygen was given, and for how long. Two of the trials had a low risk of bias other than for lack of blinding of participants and personnel. Overall all included trials had a high risk of bias.
N-acetylcysteine is an antioxidant with strong anti-inflammatory effects that is used in treating endotoxaemia and overdoses of acetaminophen. This Cochrane review of 41 randomized controlled trials with 2768 critically ill adult patients found no evidence to support the theory that N-acetylcysteine might reduce the risk of death in adults with SIRS or sepsis. Intravenous N-acetylcysteine did not affect the length of stay in the intensive care unit, duration of mechanical ventilation, duration of support for the cardiovascular system or incidence of new organ failure. There is currently insufficient evidence to support the use of N-acetylcysteine in SIRS or sepsis. We also found that when N-acetylcysteine was administered more than 24 hours after the development of clinical signs of SIRS or sepsis it may even be harmful, by causing cardiovascular depression. Twenty of the trials used N-acetylcysteine in patients around the time of surgery, including cardiac, vascular and major abdominal surgery, and liver transplantation. Eight studies evaluated N-acetylcysteine in patients with severe sepsis or septic shock associated with the medical conditions acute respiratory distress syndrome (ARDS), multiple organ failure, liver failure, malaria or burns. The dosing of N-acetylcysteine, timing and duration of treatment, from a single intravenous dose to infusions up to seven days, varied. Twenty papers had a low risk of bias.
We included 19 RCTs involving 13,209 women of childbearing age. The trials compared: - tubal rings versus clips (six RCTs, 4232 women); - partial salpingectomy versus electrocoagulation (three RCTs, 2019 women); - tubal rings versus electrocoagulation (two RCTs, 599 women); - partial salpingectomy versus clips (four RCTs, 3827 women); - clips versus electrocoagulation (two RCTs, 206 women); and - two types of clips, i.e. Hulka clips versus Filshie clips (two RCTs, 2326 women). We found no RCTs that investigated sterilisation by chemicals or tubal inserts, so all the included studies involved an abdominal operation. There were no deaths reported with any method, and major and minor morbidity were rare. Pregnancy rates were less than 5/1000 procedures one year after surgery. Complicationrates (problems after surgery/minor morbidity) were very low for all methods compared. Minor complications, including pain, and technical failures were more common with rings than clips. Major morbidity and postoperative pain were more common with partial salpingectomy than with electrocoagulation. Postoperative pain was reported twice as often by women sterilised by tubal rings than those sterilised by electrocoagulation.Technical failures were more common with clips than cutting and tying techniques, but operating time was shorter for clips. We found little evidence concerning women's or surgeon's satisfaction. Tubal sterilisation by cutting and tying the tubes, or using electric current, clips or rings, is an effective method of contraception with few problems. The choice of method will depend upon the surgeon's experience, availability of equipment, setting, and cost. More research is needed about methods for tubal sterilisation that do not require an abdominal operation.
we included seven studies (total participants = 494). All studies were on full-term, healthy infants who were breastfeeding fully or partially. There were two main comparisons: fluid supplementation via intravenous route versus no fluid supplementation and fluid supplementation via intravenous route versus oral route (by increasing feeding by mouth). Most studies did not provide enough information on certain key aspects of the methods employed. Notably, in all studies, care personnel could not be masked from knowing whether or not the infants received additional fluid, and if so through which route, and this might have affected the interpretation of results, especially those that required a person to make a judgement. none of the included studies reported funding. no infant in either the fluid supplementation or no fluid supplementation group developed clinical complications related to excessive bilirubin. Serum bilirubin was slightly lower at four and eight hours after treatment in fluid-supplemented infants. Beyond eight hours, bilirubin levels were very similar whether or not additional fluid was given. Infants who received additional fluid appeared to have shorter duration of phototherapy (on average 10.70 hours shorter, participants = 218, studies = three) and lower risk of requiring exchange transfusion (on average 1% lower, participants = 462, studies = six), but in both analyses, inconsistent results among the included studies have weakened our confidence in the overall estimates. There were no differences in breastfeeding frequencies in the first three days between infants who received additional fluid and infants who did not. In another comparison, one study showed that there were no clear differences between infants who received intravenous and oral fluid supplementation in all measurements (called outcomes), including blood bilirubin and the rate of change of bilirubin levels after four hours of study, as well as the number of infants who required exchange transfusion. there was no evidence on the major clinical outcomes of bilirubin-associated brain problems, as no infants in either group developed these problems. There was low- to moderate-quality evidence for all major outcomes. Three main factors affected the quality of evidence: first, the use of bilirubin, a laboratory measurement, as the main outcome, rather than direct clinical outcomes that matter to patients; second, inconsistent study results; and third, unpublished studies that might change the review findings for the relevant outcomes. there is no evidence that intravenous fluid supplementation affected major clinical outcomes such as acute- or long-term brain problems associated with excessive bilirubin in healthy, full-term newborn infants, mainly because the baseline risk of developing such problems was very low in this group of infants. Intravenous fluid supplementation may reduce serum bilirubin at certain time points but it is unclear whether this translates into important clinical benefits. Future research should focus on higher-risk populations such as preterm infants or infants with haemolysis (increased red blood cell breakdown which causes a rapid rise in bilirubin).
We identified 17 randomized controlled trials comparing TEG- or ROTEM-guided use of blood transfusion to guidance from the clinical judgement of doctors or standard laboratory tests, or both. The included trials were conducted mainly in adults in need of cardiac surgery, and involved 1493 participants. In terms of efficacy, the use of TEG or ROTEM tests seem to reduce the need for all types of blood transfusions. However, we could not find fewer participants in need of further operations due to continuous bleeding, or at risk of massive bleeding with transfusion. Despite signs of benefit in regards to survival, our findings are hampered by the overall low quality of included studies. Assessment of harms indicated a reduced risk of kidney failure, while no other significant adverse -events were found. However, the reported adverse event rates were very low. All included trials except two were marred by high risk of bias. Due to few events and many poorly designed trials, we consider our overall findings to be of low quality evidence in favour of TEG and ROTEM use in the management of bleeding patients.
We searched the literature up to 10 September 2014 and tried to find all available research (published and unpublished) that compared these two types of defibrillators. We only included trials with a high-quality study design to avoid the possibility of inaccurate results. Four trials (552 participants) met the inclusion criteria of our review. Several included trials were potentially at risk of misleading results due to features of their study design. When we combined these trial results, we found that using the newer biphasic waveform defibrillators may be associated with lower failure rates of restarting a person's heart, but these results were imprecise. There was no difference in the number of people who were alive on arrival at the hospital or who were discharged from the hospital alive. No included trials reported on side effects or operator safety. We are uncertain as to whether biphasic defibrillators have an important effect on being able to restart a person's heart because the results were imprecise.
This review is current to 21 March 2019. We found 14 randomized controlled studies that enrolled a total of 1844 adult participants. Six different classes of medicines were tested. These were antipsychotic drugs used as tranquillizers in ten studies; the sedative alpha2 agonist dexmedetomidine in three studies; statins that reduce cholesterol in two studies; opioids as part of pain management in one study; serotonin antagonists for nausea and vomiting in one study; and cholinesterase inhibitors, which are medicines for Alzheimer's disease, in one study. Ten studies compared medicine to placebo - an inactive medicine also known as a sugar pill; four studies compared different drugs. Eleven studies with 1153 participants reported on the main outcome of this review - duration of delirium. When drug classes were directly compared with placebo, only the alpha2 agonist dexmedetomidine was found to reduce the duration of delirium, and the cholinesterase inhibitor rivastigmine was found to prolong the duration of delirium. Each of these results is based on findings from a single small study. The other drugs when compared to placebo did not change delirium duration. The Review authors used the statistical method of network meta-analysis to compare the six different drug classes. Dexmedetomidine was ranked most effective in reducing delirium duration, followed by atypical antipsychotics. However, network meta-analysis of delirium duration failed to rule out the possibility of no difference for all six drug classes compared to placebo. Using this method, we did not find that any drug improved the duration of coma, length of stay, long-term cognitive outcomes, or death. The alpha2 agonist dexmedetomidine shortened time spent on a breathing machine. Adverse events often were not reported in these trials or were rare when reported. An analysis of reported events showed that events were similar to those reported with placebo. We found 10 ongoing studies and six studies awaiting classification that, once published and assessed, may change the conclusions of this review. Most of the included studies were small but of good design. Nine of the 14 studies were considered to have low risk of bias.
Of the seven randomised controlled trials that we found, only two trials including 186 people had useable data. The analysis of these two small trials showed inconsistent effects of aromatherapy on measures of agitation, behavioural symptoms and quality of life. More large-scale randomised controlled trials are needed before firm conclusions can be reached about the effectiveness of aromatherapy for dementia.
We searched for well-designed trials to see the effect of TENS compared to 'sham' TENS in people with SCD for relieving pain, reducing the intensity of pain, reducing the frequency of pain episodes, making a difference to the use of painkillers, improving quality of life and for assessing any adverse effects. We only found one trial (22 participants aged between 12 and 27 years). The participants were graded into four groups according to how severe their pain was. On the first visit, the participants from different groups were chosen randomly to receive either TENS or ‘sham’ TENS treatment. For a further crisis of the same severity participants were given the alternative intervention to the first one. For those experiencing a pain episode of a different severity, it is not clear which treatment they were given. Neither the participant nor the researcher were aware of which treatment was received. 30 episodes (across 22 participants) of TENS treatment and 30 of 'sham' TENS treatment were analysed. Due to low-quality data and issues with the trial design, we can only report in a descriptive way without any formal analysis. Caution should be used in interpreting these results. In the included trial no difference was found in the rating of pain on a scale of 1 to 10 at the end of one hour and four hours between the TENS and 'sham' TENS treatment groups. There was no difference between groups as to how much pain medication was used. Given the very low quality of the evidence, we are also uncertain whether TENS improves overall satisfaction as compared to 'sham' TENS. A minor adverse effect of itching was reported by only one person receiving TENS, whereas two people receiving 'sham' TENS reported a worsening of pain with the intervention. Since there is only one included trial with very low-quality evidence, we cannot state whether TENS makes any difference to managing pain in people with SCD. The trial publication did not clearly report how the randomised list for allocating the participants to the two treatment groups was generated, therefore, we assessed this as having a high risk of bias. The reporting and analysis was based on only the total number pain events and not the number of people reporting pain episodes. It is unclear from this report how many participants were crossed over from TENS to 'sham' TENS treatment group. The first treatment may have an effect on the subsequent treatment and there is no clear data regarding the cross over process from one treatment group to the other. Hence we conclude that the trial has a high risk of bias and the results are hard to interpret.
We reviewed 24 controlled clinical trials with 4631 participants investigating the effectiveness of several different Echinacea preparations for preventing and treating common colds or induced rhinovirus infections. Our review shows that a variety of products prepared from different Echinacea species, different plant parts and in a different form have been compared to placebo in randomized trials. Due to the significant differences in the preparations tested, it was difficult to draw strong conclusions. Five trials were rated as having a low risk of bias in all five categories of the Cochrane 'Risk of bias' tool. Five more trials were rated as low risk of bias, having an unclear risk of bias in only one category. Eight trials were rated as having a high risk of bias in at least one category and the remaining six as having an unclear risk of bias. The majority of trials investigated whether taking Echinacea preparations after the onset of cold symptoms shortens the duration, compared with placebo. Although it seems possible that some Echinacea products are more effective than a placebo for treating colds, the overall evidence for clinically relevant treatment effects is weak. In general, trials investigating Echinacea for preventing colds did not show statistically significant reductions in illness occurrence. However, nearly all prevention trials pointed in the direction of small preventive effects. The number of patients dropping out or reporting adverse effects did not differ significantly between treatment and control groups in prevention and treatment trials. However, in prevention trials there was a trend towards a larger number of patients dropping out due to adverse events in the treatment groups. The evidence is current to July 2013.
Our review included 10 studies (830 participants, 1387 eyes) published between 1998 and 2012. Nine of these studies investigated the ability of OCT to diagnose CSMO. Study funding sources There were no overt declarations of potential conflicts of interest in terms of the manufacturer of the OCT device being involved in funding the research. Key results We found that OCT retinal thickness measurement is not sufficiently accurate to detect CSMO, involving the centre of the macula, using clinical fundus examination as the reference standard. Of 10 patients with diabetic retinopathy, 5 of whom have CSMO, 1 of 5 with no CSMO would be wrongly diagnosed as having CSMO, and about 1 of 5 with CSMO would be missed. However, researchers have found that disagreements between OCT and clinical examination occur because OCT can detect early, subclinical retinal thickening in people without CSMO and more advanced retinopathy. They suggested that such cases of subclinical macular oedema are followed more closely, since they are at increased risk of progression to CSMO. Furthermore, OCT is an essential tool to manage antiangiogenic therapy in patients with DMO and is believed by many to be a new reference standard for its diagnosis. Quality of the evidence Study quality was often unclear because of incomplete reporting or because it was at risk of bias. Specifically, this concerned how patients were selected in the study, who referred them and how, and exclusion of those for whom poor quality images were obtained. Furthermore, many studies included both patient's eyes, which is a problem in data analyses.
On 25th October 2011, the European Medicines Agency issued a press release on the worldwide withdrawal of Xigris® (human recombinant activated protein C) from the market by Eli Lilly due to lack of beneficial effect on 28-day mortality in the PROWESS-SHOCK trial. Furthermore, Eli Lily has announced the discontinuation of all ongoing clinical trials. APC should not be used for sepsis or septic shock outside randomized clinical trials. Current evidence does not support the use of human recombinant activated protein C in adults or children with severe sepsis or septic shock; moreover, there is an increased risk of bleeding associated with its use.
This review update assessed evidence from 2641 participants in 20 randomised, double blind, placebo-controlled clinical trials of oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Oral oxycodone 10 mg plus paracetamol 650 mg provided effective analgesia. About half of those treated experienced at least half pain relief over 4 to 6 hours, and the effects lasting up to 10 hours. Higher doses gave more effect. Associated adverse events (predominantly nausea, vomiting, dizziness and somnolence) were more frequent with oxycodone or oxycodone plus paracetamol than with placebo, but studies of this type are of limited use for studying adverse effects. Limited information about oxycodone on its own suggests that it provided analgesia at doses greater than 5 mg, and that addition of paracetamol made it more effective.
Athlete's foot (tinea pedis) is a fungal infection of the feet that is easily spread and difficult to get rid of. This review compared different oral antifungal drugs (i.e. drugs taken by mouth), and it included 15 trials, involving 1438 participants. There are several different kinds of oral treatments, and the trials we found considered all the oral drugs used to treat athlete's foot. We found terbinafine and itraconazole to be more effective than placebo. And we found terbinafine to be more effective than griseofulvin. Griseofulvin is a treatment that was developed much earlier than the new treatments, such as terbinafine and itraconazole; these newer treatments tend to be most evaluated. Trials of other drugs were not large enough to show differences between them. All drugs had side-effects; gastrointestinal effects were the most common. In future clinical trials, larger numbers of participants are needed to test different treatments in order to produce more reliable data. Also, future research should consider the costs of the different treatment approaches.
Two studies met the inclusion criteria but only one contributed data to the outcomes of interest. The study was based in Denmark. Women less than 20 weeks pregnant were randomly assigned to drinking caffeinated instant coffee (568 women after exclusions) or decaffeinated instant coffee (629 women). Drinking three cups of coffee a day in early pregnancy had no effect on birthweight, preterm births or growth restriction. Both included studies were randomised controlled trials. One randomly allocated pregnant women to either caffeinated or decaffeinated groups. It was unclear from the other whether allocation concealment was undertaken. Blinding of personnel and study participants was satisfactory in both studies while blinding of outcome assessor was not clearly stated. Attrition bias was also not clearly explained in one study. The results from the one trial that provided data for analysis showed that there was no evidence of an effect of caffeine avoidance on the outcomes birthweight, preterm birth or small-for-gestational age. Two outcomes were assessed and assigned a quality rating using the GRADE methods. Evidence for these two outcomes, namely birthweight and frequency of preterm birth, was assessed as of low quality, with downgrading decisions due in part to the relatively small sample sizes and the wide confidence interval of the one included trial that contributed data. There is insufficient evidence to confirm or refute the effectiveness of caffeine avoidance on birthweight or other pregnancy outcomes.
Sixteen studies involving 3,005 people are included in this review. We did not find strong evidence that either mechanical or pharmacological interventions reduce death or clots travelling to the lungs, but we found some evidence that they can prevent clots from forming in the legs.
This review of pharmacological interventions showed that non-steroidal anti-inflammatory drugs (NSAIDs) may reduce pain in the short term, but overall pain did not improve after three months. There is conflicting evidence on the effect of glycosaminoglycan polysulphate. The anabolic steroid nandrolone may be effective, but associated risks demand extreme caution if used for patellofemoral pain syndrome, particularly in athletes.
The flu can be caused by many different viruses. One type is influenza A, with headaches, coughs and runny noses that can last for many days and lead to serious illnesses such as pneumonia. Amantadine and rimantadine are antiviral drugs. The review of trials found that both drugs are similarly helpful in relieving the symptoms of influenza A in adults, but only when there is a high probability that the cause of the flu is influenza A (a known epidemic, for example). It is likely that neither drug will interrupt the spread of influenza A and by treating symptoms may encourage viral spread in the community by people who are feeling better but are still infectious. Resistance of influenza viruses to amantadine is a serious worldwide problem as shown by recent surveys. Both drugs have adverse gastrointestinal (stomach and gut) effects, but amantadine can also have serious effects on the nervous system. They should only be used in an emergency when all other measures fail.
We identified 10 studies involving 878 participants. Twenty-eight participants were lost to follow-up. The evidence is current up to 27 October 2015. All participants were recruited from intensive care units (ICUs) and received mechanical ventilation for more than 48 hours. Moderate quality evidence from eight studies involving 759 participants demonstrated that a semi-recumbent (30º to 60º) position reduced clinically suspected VAP by 25.7% when compared to a 0° to 10° supine position. Based on this result, we would expect that out of 1000 critically ill adult patients who are nursed in the semi-recumbent position (30º to 60º) for more than 48 hours, 145 patients would experience clinically suspected VAP compared to 402 patients nursed in the 0° to 10° supine position. There was no significant difference between the two positions in reducing microbiologically confirmed VAP (very low quality evidence), mortality (low quality evidence), length of ICU stay (moderate quality evidence), hospital stay (very low quality evidence), duration of ventilation or use of antibiotics. The main limitations of the evidence were the small numbers of participants contributing data to the analyses and that for some studies researchers would have known which treatment group participants were from (a risk of bias). Only two studies with 91 participants compared different degrees of bed head angle (45° versus 25° to 30° semi-recumbent position). Very low quality evidence showed no statistically significant differences in the effects of VAP (clinically suspected and microbiologically confirmed), mortality (ICU and hospital), length of ICU stay or use of antibiotics. Only one study reported the adverse event of pressure ulcers and did not find a difference between the 45° semi-recumbent and 10° supine positions. No other adverse events, such as thromboembolism, or side effects on heart rate or blood pressure were reported. The balance of the benefit and harm of semi-recumbent positioning still remains uncertain due to the limited numbers of studies and the low quality of the existing evidence. More high quality evidence is required on the effects of the semi-recumbent versus supine position and the optimal body positions.
Its use in newborn babies is studied in only one study of 63 babies. Propofol helped to reduce time to complete procedure, time of recovery and time to prepare drugs. However, with this small number of newborns studied, the safety can not be proven. Further studies are warranted.
This review identified three trials (involving 360 women and their infants), but one trial did not provide any relevant data. The trials were small and were assessed as being at a low or unclear risk of bias. The trials did not report many outcomes of relevance to this review. We did find limited evidence to suggest that when magnesium sulphate was given to mothers in preterm labour, differences in the dose (high-dose versus low-dose) did not impact on the number of babies that died (very low quality evidence). There were no data to assess other important outcomes: birth less than 48 hours after entry to the trial, or serious outcomes for mothers or their babies. The included trials provided very few data for other outcomes relevant to this review (overall, we were only able to examine eight of the 45 outcomes we wanted to examine). One trial did find that the rate of newborn respiratory distress syndrome (low quality evidence) and the length of stay in the neonatal intensive care unit were reduced with high-dose magnesium sulphate (compared to the babies born to the group of women who were given low-dose magnesium sulphate). However, this result is based on evidence from one small study and should therefore be interpreted with caution. The rate of caesarean birth did not differ between those women given high-dose and those women given low-dose magnesium sulphate. Nor were there any differences between groups in terms of the number of babies that died before birth or during the subsequent month or the number of babies with low levels of calcium in their blood, low bone density or bone fractures. The frequency of self-reported adverse effects in mothers including flushing, headache (two trials, 248 women), or nausea and vomiting (one trial, 100 women) did not differ between high-dose and low-dose magnesium sulphate groups. Pulmonary oedema was reported in two mothers given high-dose magnesium sulphate, and in none of the mothers given low-dose magnesium sulphate. No trials have looked at different durations of treatment, timing and other ways of giving magnesium sulphate to mothers going in to labour too early. Further trials are needed to address the lack of evidence regarding the best dose, duration of therapy, timing of therapy and role for repeat dosing in terms of efficacy and safety for mothers and their children.
We conducted a systematic review to assess whether or not cisapride actually relieves constipation and controls the symptoms of irritable bowel disease, in addition to looking at whether or not these effects are worth its use compared to the risk of cisapride's dangerous side effects. Through a detailed look at the literature, we found no clear evidence to suggest that cisapride has a role in controlling symptoms related to constipation or IBS and believe its not worth the risk of its possibly fatal arrhythmia side effects.
We looked for trials comparing supplements with placebo (dummy). We included 11 randomised controlled trials (596 participants) when it was clear that the children or adults taking part had atopic eczema. In reviewing the trials, the main outcomes we looked for were evidence of improvement in the symptoms of eczema, such as itching or loss of sleep, in the short-term (i.e. six weeks). In the longer term, we wanted to see evidence of a reduced need for treatment for the eczema or a reduction in the number of flares. We also looked for evidence of any general improvement in the eczema and in individual symptoms. Overall, we found no convincing evidence that taking supplements improved the eczema of those involved. In general, studies were small with low numbers of participants and of poor quality in terms of the way they were run. Two trials of fish oil did find slight improvement for the participants in terms of the degree of itchiness and quality of life. However, these trials had small numbers, which means they had little chance of finding real differences if they did exist. That is why larger trials are needed before any recommendations can be made. We found no evidence of adverse (harmful) effects in those who took part in the trials. People sometimes think that supplements can at least do no harm; however, high doses of vitamin D, for example, can cause serious medical problems, and the safety of dietary supplements should not be assumed. The cost of supplements can also mount up.
Six published randomised controlled trials met our inclusion criteria, with a total of 1177 infants enrolled. This update includes the results from two high-quality studies conducted in 760 infants of less than 30 weeks' postmenstrual age (PMA). In our previous update of our review, in 2015, we found that the initial evidence regarding inositol supplementation in preterm babies with RDS was promising. Inositol supplementation lowered rates of death and bleeding in the brain, with an important reduction in eye problems as well. Inositol did not have serious adverse effects. We suggested that further research was warranted to confirm these preliminary findings. Such research has now been published from two high-quality studies that included 760 infants of less than 30 weeks' PMA, the most vulnerable population. All results indicate that there are no reductions in adverse outcomes associated with inositol supplementation, including infant death, eye problems, bleeding in the brain, infections, chronic lung problems and gastrointestinal problems. Thus inositol supplementation in preterm infants is not recommended. Infants enrolled in these studies should be followed into childhood for assessment of any neuro-developmental problems. According to GRADE (a method to score the quality of the trials supporting each outcome), the quality of the evidence varied but was moderate to high for the important outcomes in the analyses for repeated high doses of inositol in infants born at less than 30 weeks' postmenstrual age.
Two studies had deaths reported, comprising of four persons in the control group, and eight in the AZA group. These small numbers do not allow a statistical analysis.  Conflicting conclusions on potential risk of cancer in MS patients with long-term AZA treatment have been reported in eight published papers, not considered in the present review because they came from sources other than clinical trials. The presence of patients who developed cancer ( three in the AZA and 1 the placebo group) was reported in two out of five studies considered in this review. Numerous studies of AZA treated patient populations other than MS patients are also available. The whole data, however, does not show an increase in risk of malignancy from AZA. Possible long-term risks may be related to a treatment duration above ten years and cumulative doses above 600 g.
We found five randomised controlled trials comparing timed intercourse versus intercourse without ovulation prediction, in a total of 2840 women or couples trying to conceive. The evidence was current to August 2014. One large included study (1453 women) has not published usable results and could therefore not be analysed. One study reported live birth rates and found no evidence of a difference; however, the study was too small to have any clinical value. Only one study reported levels of stress and showed no evidence of a difference between timed intercourse with urinary fertility monitoring and intercourse without urinary fertility monitoring. No other adverse events were reported. Only two studies reported clinical pregnancy rates, and showed no evidence of a difference in pregnancy rates in couples with subfertility. The evidence suggested that if the chance of a clinical pregnancy following intercourse without ovulation prediction was assumed to be 16%, the chance of a clinical pregnancy following timed intercourse would be between 9% and 33%. However, if including self-reported pregnancies (not confirmed by ultrasound), pregnancy rates were higher after timed intercourse. The evidence suggested that if the chance of a pregnancy following intercourse without ovulation prediction was 13%, the chance following timed intercourse would be between 14% and 23%. No difference in effect was found between couples trying to conceive for less than 12 months versus 12 months or more. One trial reported time to conception data and showed no evidence of a difference in time to conception. The overall quality of the evidence ranged from low to very low for all outcomes. The main limitations of the evidence were imprecision, poor reporting of clinically relevant outcomes and a high risk of publication bias, as one large study remains unpublished. Therefore, the findings should be regarded with caution.
We found 12 studies including 854 women that examined the effect of exercise in women with period pain. The evidence is current to August 2019. Two trials did not report data suitable to be included in the meta-analysis, so we included 10 trials with 754 women in our meta-analysis. Eleven trials compared exercise with no treatment and one compared exercise with NSAIDs. Exercise, whether low-intensity, such as yoga, or high-intensity, such as aerobics, may provide a large reduction in the intensity of period pain, compared to not doing anything. This reduction in pain was likely to be important to women with period pain as it is over twice the minimum amount of pain reduction we think is needed to notice a difference. Most studies asked women to exercise at least three times per week, for about 45 to 60 minutes of exercise each time. It is unclear if exercising less frequently, or for a shorter duration would have the same results. Exercise was performed regularly throughout the month, with some studies asking women not to perform exercise during the period itself. The evidence for the safety of exercise was not well reported and so we cannot draw any conclusions. Other outcomes, such as the effect on overall menstrual symptoms or overall quality of life, were not well reported and the evidence was of very low quality, so we cannot be sure if exercise has any effect on these outcomes. No studies reported on rates of being absent from work or school or on restrictions of daily life activities. There was not enough evidence to determine if there was any benefit of exercise when compared to NSAIDs, a class of medications (like ibuprofen) commonly used to treat period pain, on menstrual pain intensity, need for additional pain-relieving medication, or absence from work or school. No studies reported on quality of life or restriction of daily life activities The quality of the evidence was low to very low. The main limitations were imprecision due to small sample sizes (too few women in the study), inconsistency (studies gave very different results) and risk of bias related to blinding (where researchers or participants knew what treatment they were getting).
In this review we summarized studies of antidepressant drug treatments in patients with MS. We found two studies that met the inclusion criteria of methodological quality, comprising of a total of 70 participants: one (28 participants) reported the effects of desipramine, the other (42 participants) the effects of paroxetine. The two studies showed no improvement of depression with both treatments in the short term (five/twelve weeks). Adverse effects, such as nausea or headache occurred frequently. Further studies on drug treatment of depression in MS with a longer duration are clearly needed, as the results may be affected by the small size of participants and by the fact that many participants did not complete the studies.
The evidence is current to February 2016. In this update we identified 10 completed trials that compared giving white blood cell transfusions to treat infection compared to not giving white blood cells to treat infection. One additional trial has not yet been completed. The 10 trials containing a total of 587 participants were conducted between 1975 and 2015. The studies differed in the type of infections they included. Data from three trials were not included in the analyses because participants were included within the trial more than once. Six trials included both children and adults, but results were not reported separately for children and adults. The two newest trials gave G-CSF to donors, both were stopped early due to lack of recruitment. Six studies reported their funding sources and all were funded by governments or charities. Giving white blood cell transfusions to treat infection may not affect the risk of death or the number of people who recover from an infection. It is unknown whether white blood cell transfusions increase the risk of having a serious adverse event. None of the studies reported whether white blood cell transfusions reduced the number of days participants were on therapeutic antibiotics, or whether white blood cell transfusions had an effect on participants' quality of life. The evidence for most of the findings are of low or very low quality. This was because the total number of participants included in this review was too small to detect a difference in this review's primary outcome. We calculated that a study would need at least 2748 participants to be able to detect a decrease in the risk of death from 35 people out of 100 to 30 people out of 100 (five additional lives saved per 100 people treated). Also participants and their doctors were likely to know which study arm they had been allocated to in all of the studies.
We found 26 studies with 2272 participants receiving home-based multidimensional survivorship programmes compared with control. The content and delivery approach of the home-based multidimensional survivorship programmes were diverse among the included studies. The survivorship programme could incorporate any combination of at least two of the three identified components: educational (such as the provision of information and advice on how to self-manage); physical (such as exercise or resistance training); and psychological (such as counselling and cognitive therapies). Most of the studies used usual care (routine medical follow-up services) as a comparator. A few studies used a lower level or different type of intervention (e.g. stress management or exercise) or attention control as the comparator. The results revealed that home-based multidimensional survivorship programmes in breast cancer survivors appear to have a short-term beneficial effect of improving quality of life. Several other studies examined the effects of home-based multidimensional survivorship programmes on symptoms and psychosocial outcomes. Those breast cancer survivors who received home-based multidimensional survivorship programmes showed a reduction in fatigue, insomnia and anxiety, but the effect was in the short term. There was no difference between groups with respect to symptoms of depression, flushes and night sweats. We found that a group-based approach may be more effective than an individual-based approach to deliver the home-based multidimensional survivorship programmes. However, we found no evidence for a difference in quality of life with educational, psychological or physical components of the survivorship programmes. The quality of evidence across studies for quality of life ranged from moderate to very low, meaning that in some cases we were fairly confident about the results (e.g. quality of life improvements) while in other cases we were uncertain about the results (e.g. reductions in fatigue, insomnia and anxiety).
Twenty three trials with 3685 participants were included in the review. Participants were more likely to improve if they were using an anticholinergic drug compared with bladder training alone, and also when using a combination of an anticholinergic drug plus bladder training. More people reported an improvement in their overactive bladder symptoms when using electrical stimulation than an anticholinergic drug, but this was only significant in one trial for one type of electrical stimulation, percutaneous posterior tibial nerve stimulation. These results have to be viewed with caution as different types and doses of the anticholinergic drugs were used in the trials. The main adverse effect reported was dry mouth, in about a third of the people taking an anticholinergic drug.
We found one trial involving 75 preterm infants with very low-quality evidence on the effects of adding extra prebiotics (a type of carbohydrate) to human milk in preterm infants. A second publication by the same study authors reported different methods regarding blinding and randomisation of the trial. Study authors confirmed that these publications describe the same trial but have not yet clarified which method is accurate. We were unable to reproduce the analyses from the data presented. The search is up-to-date as of February 2018. Prebiotic carbohydrate supplementation increased the mean weight of preterm infants at day 30 and resulted in a shorter hospital stay compared with control. No evidence shows a clear difference in risk of feeding intolerance or necrotising enterocolitis between the prebiotic-supplemented and unsupplemented groups. No other data were available to show the effects of adding extra carbohydrate to human milk on short- and long-term growth, body fat, obesity, brain development, and heart problems. Evidence on the short- and long-term effects of adding extra carbohydrate to human milk in preterm infants is lacking. This systematic review found very low-quality evidence on the effects of adding prebiotic carbohydrate to human milk in preterm infants, along with uncertainties about methods and analysis. The single trial included a small sample of Iranian preterm infants, and so the evidence may be considered as not generalisable. However, the outcomes assessed are common to all preterm infants, and the trial shows that adding prebiotic carbohydrate to human milk is possible in developing countries. Further research is needed to assess the benefits and harms of different types and concentrations of carbohydrate supplementation for preterm infants fed human milk. Currently, digestible carbohydrate supplementation in preterm infants is provided as a component of multi-nutrient human milk fortification. Hence we do not plan to publish further updates of this review.
We found only one small randomized controlled trial that compared early feeding (within 24 hours of injury) with conventional feeding (after at least 48 hours). The trial showed no differences between the groups for any of the outcomes examined. Further research in this area is urgently needed to help guide optimal treatment of children with critical illness. In a recent search update (February 2016) we identified a protocol for a relevant randomized controlled study; however, no results have yet been published.
This review found six mostly small studies with some limitations in their methods. All six studies were conducted in the neonatal nursery of a major tertiary hospital. In all studies, researchers enrolled preterm infants of average postmenstrual age of 29 weeks (nearly two and a half months preterm). Some studies enrolled twins only; others enrolled twins and triplets and quadruplets and chose to co-bed two of the higher-order multiples considered most stable at the time of enrollment. Overall, researchers reported no differences between the co-bedded group and the group receiving care separately in terms of weight gain, episodes of major disturbances in their breathing, heart rate or oxygenation level (apnea, bradycardia, or desaturation episodes), length of hospital stay, and occurrence of infection. Conflicting results were noted in the two included studies that assessed infants' pain response after heel prick. Overall quality of evidence was low because of limitations in study methods, small sample sizes giving rise to imprecise results, and inconsistency in study results. We can make no recommendations for or against co-bedding for stable preterm twins in the neonatal nursery on the basis of evidence gathered in this review. Further research on this topic is needed.
There was evidence of benefit that selective serotonin reuptake inhibitors (SSRIs) were more effective than placebo, although the evidence was of very low quality. There was also evidence of benefit for monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMAs), and benzodiazepines, even though the evidence was low in quality. The anticonvulsants gabapentin and pregabalin also showed moderate-quality evidence of a clinical response. We did not observe this effect for the remaining medication classes. The SSRIs were the only medication proving effective in reducing relapse based on moderate-quality evidence. There was low-quality evidence that more people taking SSRIs and SNRIs dropped out due to side effects than those taking placebo, but absolute withdrawal rates were low. For the outcome of SAnD symptom severity, there was evidence of benefit for SSRIs, the serotonin and norepinephrine reuptake inhibitor (SNRI) venlafaxine, MAOIs, RIMAs, benzodiazepines, the antipsychotic olanzapine, and the noradrenergic and specific serotonergic antidepressant (NaSSA) atomoxetine, but most of the evidence was of very low quality. SSRIs and RIMAs reduced depression symptoms, and SSRIs reduced functional disability across all domains. We also observed response to long-term treatment with SSRIs (based on low-quality evidence), MAOIs (based on very low-quality evidence), and RIMAs (based on moderate-quality evidence). Most evidence for treatment efficacy is related to SSRIs. Nevertheless, SSRI trials were associated with very low-quality evidence and high risk of publication bias. It would be useful for future studies to evaluate the treatment of SAnD in people with comorbid disorders, including substance use disorders. Trials that provide adequate information on randomisation and allocation concealment are needed.
This review of three studies involving 470 participants found little evidence of how this care is best delivered. Information on a small number of nursing home residents who had a stroke (67 participants from a larger trial) showed that training nursing staff improved their knowledge of oral care and resulted in improved oral hygiene in their patients. Another trial demonstrated the beneficial impact of a decontamination gel on the incidence of pneumonia amongst patients in a stroke ward. However, there was no other information on how best to provide oral hygiene and more studies are urgently needed.
The review authors identified four trials, with 116 participants, investigating the effectiveness of compressing therapies for PTS (most recent search 2 July 2018). Two trials studied the effect of GECS. One study showed an improvement of PTS symptoms and one showed no benefit. Two other trials studied the effect of an intermittent pneumatic compression device. Both reported an improvement in PTS severity. One study evaluated side effects and quality of life. Although 9% of the participants experienced side effects such as leg swelling, irritation, superficial bleeding, and skin itching, quality of life had positive outcomes. None of the studies assessed or reported on patient satisfaction or compliance rates. The evidence for use of GECS or intermittent pneumatic compression device compared to control for the treatment of PTS severity is of very-low and low-certainty reliability. This is due to conflicting results, small studies of short duration, and differences in how the studies measured outcomes. Limited evidence was available for side effects, patient satisfaction, quality of life, and compliance.
This review found 81 relevant studies that recruited over 9000 participants in total. The studies mainly focussed on people having bowel surgery or caesarean section, but there were some studies of other surgery types. There were few studies of children. Most studies were of poor quality, which may mean their results are less reliable. We found some evidence that people who chewed gum after an operation were able to pass wind and have bowel movements sooner than people who did not chew gum. We also found some evidence that people who chewed gum after an operation had bowel sounds (gurgling sounds heard using a stethoscope held to the abdomen) slightly sooner than people who did not chew gum. There was a small difference in how long people stayed in hospital between people who did or did not chew gum. There were no differences in complications (such as infection or death) between people who did or did not chew gum. There was also no difference in the overall cost of treatment between people who did or did not chew gum. There is some evidence that chewing gum after surgery may help the digestive system to recover. However, the studies included in this review are generally of poor quality, which meant that their results may not be reliable. We also know that there are many factors affecting ileus, and that modern treatment plans attempt to reduce risk of ileus. Therefore to further explore using chewing gum after surgery, more studies would be needed which are larger, of better quality, include different types of surgery, and consider recent changes in health care systems.
In this systematic review of non-randomised studies, no benefit could be demonstrated for CD over vaginal delivery (VD) in the prevention of anal incontinence. This review encompasses 21 published studies, involving 31,698 women, delivered by 6,028 CD and by 25,170 VD. No randomised studies comparing CD to VD in average risk pregnancies exist. The above conclusion is therefore based upon less than optimal evidence.
In evidence current to September 2016, we found one trial that primarily tested if brain oxygenation can be stabilised by combining NIRS measurements of the brain with a treatment guideline on how to intervene when the brain oxygenation is outside the normal range. The 166 infants included were born more than 12 weeks before term. They were monitored during the first three days of life. The study was funded by government agency, and we found that the methods used in trial were as good as possible. The single trial we found showed a large and significant difference in brain oxygenation between the experimental group and the control group. Low oxygenation was far more common in the control group. It did not, however, find that monitoring with NIRS reduces mortality or the occurrence of the most common complications of very preterm birth, i.e. intracranial bleedings, chronic lung disease, damage of the intestines (necrotising enterocolitis), and blindness (retinopathy of prematurity). The NIRS monitoring did not cause serious harm, but skin marks from the NIRS sensor were seen in about 1 in 10 patients. The accrued information size with one small randomised trial is too small to conclude anything about the benefits and harms of cerebral near-infrared spectroscopy in preterm infants. Thus further studies are needed.
This review is based on five randomised trials; four comparing methotrexate with placebo, and one comparing methotrexate with colchicine. Methotrexate, compared with placebo, has no significant beneficial effect on mortality and the need for liver transplantation is not significantly reduced. The effects of methotrexate on pruritus, fatigue, clinical complications, liver biochemistry levels, liver histology, and adverse events were not significantly different from placebo. There may be some beneficial effect on pruritus score (ie, an objective measure of subjective feeling of pruritus), but we cannot recommend methotrexate for this indication only, taken into account possible adverse events. In the small trial comparing methotrexate versus colchicine, methotrexate seemed to work superior to colchicine, but it is not clear if this stems from the fact that methotrexate exerts beneficial effects as colchicine exerts harmful effects. In comparison with both placebo and colchicine, methotrexate was associated with large risks of mortality and adverse events, but the increase did not reach statistical significance.
After an extensive review of medical literature we identified three trials assessing different treatment strategies for patients with BM from SCLC. Only one of the studies compared chemotherapy (topotecan) versus no chemotherapy, but in patients treated with whole brain radiotherapy. Another study randomized patients to receive teniposide with or without brain radiation therapy, and the third one, compared sequential and concomitant chemoradiotherapy (teniposide plus cisplatin). Studies show that people who received chemotherapy did not live longer or have a longer time before the BM grew again compared to those who were treated with brain radiation therapy alone. Hematological toxicities occurred more often in patients exposed to chemoradiotherapy in one study and in patients receiving sequential treatment in another study. A major limitation of this review was the low number of included studies and participants.
The review found some evidence that hGH does increase short-term growth in girls with TS and adult height (an increase of perhaps five centimeters or two inches). However, girls treated with hGH are still substantially shorter than other women as adults. Final height in 61 treated women was 148 cm and 141 cm in 43 untreated women.
This evidence is current to 4 December 2015. We found 39 trials that recruited 16,082 participants testing 22 different multi-component interventions, medications or anaesthetic interventions, compared to usual care, placebo, or different interventions. We found strong evidence that multi-component interventions can prevent delirium in both medical and surgical settings and less robust evidence that they reduce the severity of delirium. Evidence about their effect on the duration of delirium is inconclusive. There is evidence that monitoring the depth of anaesthesia can reduce the occurrence of delirium after general anaesthetic. We found no clear evidence that a range of medications or other anaesthetic techniques or procedures are effective in preventing delirium. There is moderate-quality evidence to indicate that multi-component interventions reduce the incidence of delirium. The evidence supports implementing multi-component delirium prevention interventions into routine care for patients in hospital. There is moderate-quality evidence that monitoring depth of general anaesthesia can be used to prevent delirium postoperatively. The quality of the evidence for a range of medications or other anaesthetic techniques or procedures for preventing delirium is poor (because of the small number of trials and the variable quality of trial methods), and cannot be used to inform changes to practice. None.
We searched for randomized controlled studies of immediate and early SSC on 17 December 2015. We found thirty-eight studies with 3472 women that provided data for analysis. Most studies compared early SSC with standard hospital care for women with healthy full-term babies. In eight studies women gave birth by cesarean, and in six studies the babies were healthy but born preterm at 35 weeks or more. More women who had SSC with their babies were still breastfeeding at one to four months after giving birth (14 studies, 887 women, moderate-quality evidence). Mothers who had SSC breast fed their infants longer, too, on average over 60 days longer (six studies, 264 women, low-quality evidence). Babies held in SSC were more likely to have breast fed successfully during their first breast feed (five studies, 575 women). Babies held in SSC had higher blood glucose levels (three studies, 144 women, low-quality evidence), but similar temperature to babies with standard care (six studies, 558 women, low-quality evidence). We had too few babies in our included studies and the quality of the evidence was too low for us to be very confident in the results for infants. Women giving birth by cesarean may benefit from early SSC, with more women breastfeeding successfully and still breastfeeding at one to four months (fourteen studies, 887 women, moderate-quality evidence), but there were not enough women studied for us to be confident in this result. We found no clear benefit to immediate SSC rather than SSC after the baby had been washed and examined. Neither did we find any clear advantage of a longer duration of SSC (more than one hour) compared with less than one hour. Future trials with more women and infants may help us answer these questions with confidence. SSC was defined in various ways and different scales and times were used to measure different outcomes. Women and staff knew they were being studied, and women in the standard care groups had varying levels of breastfeeding support. These differences lead to wide variation in the findings and a lower quality evidence. Many studies were small with less than 100 women participating. The evidence from this updated review supports using immediate or early SSC to promote breastfeeding. This is important because we know breastfeeding helps babies avoid illness and stay healthy. Women giving birth by cesarean may benefit from early SSC but we need more studies to confirm this. We still do not know whether early SSC for healthy infants helps them make the transition to the outside world more smoothly after birth, but future good quality studies may improve our understanding. Despite our concerns about the quality of the studies, and since we found no evidence of harm in any included studies, we conclude the evidence supports that early SSC should be normal practice for healthy newborns including those born by cesarean and babies born early at 35 weeks or more.
We wanted to know whether any treatments were successful in improving pain, and reducing disability and distress in survivors of torture. We searched the academic literature to February 2017 and found three randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups). Two studies (58 participants) compared cognitive behavioural therapy (CBT; talking therapy that helps people change the way they think and behave) plus learning to control muscles and breathing with no treatment, and we were able to combine these for analysis. Neither study showed any meaningful improvement in pain, reduction in disability, or reduction in distress, over eight to 13 weeks of treatment. One study (30 participants) compared complex manual therapy with self-treatment for low back pain but could not be combined with the other two studies; it reported no difference in pain relief, but did report that the physical intervention reduced disability and distress at the end of treatment. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low quality evidence means that we are very uncertain about the results. High quality evidence means that we are very confident in the results. The quality of the evidence was very low for pain relief, reduction in distress, and reduction in disability. This was due to the small size of the studies, poor study design, and substantial dropout of participants from studies.
In this updated review, we identified 10 studies involving a total of 1015 participants. We did not find any well-designed randomized controlled trial evidence to support the use of these medications. Trials of antioxidants identified in this review were generally of poor methodological quality and lacked statistical power. However, antioxidants are generally well tolerated without serious adverse effects.
This review examines the benefits and costs of outreach in a range of specialties and in a variety of settings. Simple 'shifted outpatients' styles of specialist outreach were shown to improve access, but there was no evidence of their impact on health outcomes. Outreach as part of more complex multifaceted interventions involving primary care collaborations, education and other services was associated with improved health outcomes, more efficient and guideline-consistent care, and less use of inpatient services. There is a need for better quality evidence evaluating specialist outreach in all settings, but especially in rural and disadvantaged populations.
We searched scientific databases for studies comparing NCPAP versus NIPPV in preterm infants (born before 37 completed weeks of pregnancy) who no longer need an endotracheal tube. We looked at breathing problems, the need for the endotracheal tube to be re-instated and side effects. Evidence is current to September 2015. We found ten trials comparing NCPAP versus NIPPV. Six of ten studies that compared NCPAP and NIPPV showed that NIPPV reduced the need for re-insertion of the endotracheal tube. Future studies must determine how NIPPV can best be delivered to infants. In clinical trials, clinicians and investigators were aware of the intervention received by each infant (NIPPV or NCPAP). Therefore, we graded the quality of evidence for the primary outcome (breathing problems and need for re-insertion of the endotracheal tube) as moderate.
We found four studies that randomly allocated 389 patients to receive ECMO versus conventional lung support. All studies comprised patients with acute lung failure. We found no completed study in patients with acute heart failure or arrest. We found one ongoing study in patients with acute lung failure and two ongoing studies in patients with acute heart failure (arrest). The evidence is current to August 2014. Clinical differences in the care provided for patients with acute lung failure prevented us from combining the results of individual studies. Individual studies reported no differences in all-cause death at or before six months in patients given ECMO compared with those who were not. In one study survival was low in both groups but none of the patients who survived had limitations in their daily activities six months after discharge. Another study found improved survival without severe disability in patients transferred to an ECMO centre for consideration of ECMO six months after study entry. In three studies, patients in the ECMO group received greater numbers of blood transfusions. One study reported more non-brain bleeding in the ECMO group, and another study reported two serious adverse events in the ECMO group. Another study reported three adverse events in the ECMO group. Clinical practice, study planning and ways of using ECMO have varied considerably among studies. Technological developments (circuits, pumps and mechanical lungs) have improved performance and patient safety with ECMO applications over time. These clinical differences in the care provided for patients with acute lung failure prevented us from combining the results of individual studies. In critically ill adults, ECMO may or may not be more effective in improving survival compared with conventional lung support. Results from ongoing studies will help us better understand the role of ECMO and ECPR in the treatment of patients with acute lung or heart failure.
The evidence on which this review is based is up to date as of 15 May 2018. We found six relevant articles to include in this review. All are related to one single study conducted in Hong Kong between 2002 and 2008. The study involved 47 participants aged 13 to 45 years of age. It investigated the effects of the two surgical procedures on alteration of face morphology, stability of upper jaw after surgery, speech and velopharyngeal function (ability to close the gap between the soft palate and nasal cavity to produce sound), psychological status of the participants and clinical side effects. Both procedures were effective in producing better facial structure in cleft patients. Upper jaw was more stable in the distraction osteogenesis group than the conventional osteotomy group five years after surgery. There was no difference in speech and velopharyngeal function between the procedures. Social self esteem in the maxillary distraction group initially seemed to be lower than in the conventional surgery group, but this improved over time and the distraction group had higher satisfaction with life two years after surgery. Side effects included deterioration of the fit between the teeth when the mouth is closed and infection of muscous membranes of the nose and mouth, but the frequency of these problems was similar between groups. There was no severe harm to any participant. We judged the quality of the evidence to be very low. The one study was small and there were concerns about aspects of its design and reporting; therefore we have found no reliable evidence as to which procedure should be regarded superior. High quality clinical trials, which involve lots of people, and different face types, are required to guide decision making.
Six trials which investigated the effect of ketanserin on 146 patients with either primary Raynaud's phenomenon or Raynaud's phenomenon secondary to systemic sclerosis were included (Cadranel 1986; Dormandy 1988; Kirch 1987; Lukac 1985; Ortonne 1989; van de Wal 1987). Patients treated with ketanserin experienced a greater improvement in mean functional index scores and more patients improved than those treated with placebo, however they also experienced more side effects and an increase in the frequency and duration of attacks. This review assessed a limited number of studies and therefore the conclusions reached need to be investigated further.
We searched for scientific research studies known as 'randomised controlled trials', up to 17 September 2019. In this type of study, participants are assigned in a random way to an experimental or control group. People in the experimental group receive the treatment being tested, and people in the control group usually receive either no treatment, placebo (fake treatment), another type of treatment or routine care. We found two studies to include in our review. One study assessed 165 participants who did not have cardiovascular diseases, but had metabolic syndrome (a combination of risk factors for cardiovascular disease, such as obesity, high blood pressure, and high blood sugar). The other study started off with 303 participants who had cardiovascular diseases, but after a year, only 37 participants were assessed and so we thought the results were not be reliable enough to be used. Both studies had problems with their design, and we judged them to be at high risk of bias. For people who have metabolic syndrome but no cardiovascular diseases, we were unable to determine whether treating chronic periodontitis, by removing the plaque and tartar ('scaling') from the roots of teeth and giving antibiotics, reduced the risk of dying or having cardiovascular attacks when compared with scaling the teeth from above the gumline only. For people with cardiovascular diseases and chronic periodontitis, we found no reliable evidence about the effects of periodontal treatment. We classified the evidence as 'very low certainty'. We are uncertain about the findings because there are only two small studies, at high risk of bias, with very imprecise results. Overall, we cannot draw any reliable conclusions from the findings. Further research is needed.
We found 30 trials involving 4691 participants, examining several types of contracts. The main health problems targeted were substance addictions, hypertension and overweight. Many of the trials were of poor quality and involved small numbers of people. Most were conducted in the USA. In 15 of the trials there was at least one outcome showing statistically significant differences in favour of the contracts group (although some of the improvements in adherence did not remain when measured after a longer period). In six trials at least one outcome showed such differences in favour of the control group. In 26 trials there was at least one outcome for which there was no difference between the contract and control groups. There is not enough reliable evidence available to recommend the routine use of contracts in health services to improve patients' adherence to healthcare activities or other outcomes.
Following meticulous searches of major databases (all databases searched June 2013, MDSG register last searched June 2014) and conference proceedings we were able to locate four trials, with a total of 1392 women. These were all prospective, randomised controlled trials comparing two competing post-ET interventions or an intervention versus no treatment on clinical outcomes in women undergoing IVF and ICSI. Each study recruited from 164 to 639 infertile women of reproductive age and all were conducted in IVF centres; none of them had conflicts of interest regarding study funding. Our primary measure of success, live birth rate, was not reported in any of the included trials. There was insufficient evidence to support a specific length of time for women to remain recumbent, if at all, following ET, nor was there sufficient evidence to recommend the use of fibrin sealants. There was very limited evidence to support the use of mechanical pressure to close the cervical canal. Further large well-designed studies are required to determine the true effectiveness and safety of these interventions. There was no evidence that any of the interventions had an effect on adverse event rates, but data were too few to reach any conclusions. The quality of the evidence was low or very low for all comparisons. The main limitations were failure to report live births, imprecision and risk of bias. Study risk of bias was variable, with the reporting of a proper method of randomisation and allocation concealment demonstrated in most trials while only one trial clearly blinded both the patients and the clinicians to the intervention received.
Herbal preparations are commonly used alternatives to drug treatment, surgery, or both. This systematic review included 21 randomised clinical trials involving 2222 women with uterine fibroids. There is no evidence on the effectiveness of herbal preparations for symptom relief as no trials evaluated this properly. Compared with conventional medication, one herbal preparation, Tripterygium wilfordii, may have a more beneficial effect in reducing the volume of uterine fibroids. Another five herbal medicines appeared to be similar to conventional medication in reducing the volume of fibroids. The herbal medicine Guizhi Fuling formula showed a significantly greater effect in reducing the volume of the fibroids when combined with mifepristone versus mifepristone alone. However, these clinical trials were small in terms of the number of participants and the trial quality was low. Thirteen out of 21 included trials reported on adverse effects of herbal preparations and found some minor problems such as stomach discomfort, nausea, hot flushes, and poor appetite although no serious adverse effects were identified. The effect of herbal preparations for uterine fibroids is therefore not confirmed in this review and needs to be studied in large, good quality trials.
Previous small studies and unsystematic reviews have found no difference between the various first- generation antipsychotic drugs. This has led to the assumption that these drugs are similar in effectiveness (despite observations by psychiatrists and health professionals that these drugs do sometimes differ in their effectiveness and side effects). Because of high prescription-rates, research on haloperidol is very important. A search for randomised trials was run in 2012. This review includes 63 trials with 3675 participants. Haloperidol was compared with a large number of other first-generation antipsychotic drugs (including bromperidol, loxapine and trifluoperazine) to assess its effectiveness, acceptability and tolerability. The findings of the review support the evidence of previous small, narrative studies and unsystematic reviews. There was no difference between haloperidol and other mainly high-potency first-generation antipsychotic drugs. In addition, haloperidol was characterised by a similar risk profile and side effects to other first-generation antipsychotic drugs. People receiving haloperidol were less likely to experience akathisia in the medium term. Occurrence of other specific side effect such as tremor, dystonia, dyskinesia and rigor were all similar between treatment groups. Psychiatrists and people with schizophrenia should know that haloperidol and other first-generation antipsychotic drugs are similar in their effectiveness and risk of side effects. These drugs should also be similar in their acceptability for people with schizophrenia. However, results were limited due to the low quality of many of the included studies and low quality of evidence provided. Future studies of higher quality are required. This plain language summary has been written by a consumer Ben Gray: Senior Peer Researcher www.mcpin.org.
Four studies at unclear to high risk of bias comprising 463 participants were included. The mean study duration was 7.5 months (range 3 to 18 months). None of the studies addressed our key primary outcome－'health-related quality of life'. Two of our secondary outcomes－'change from baseline in levothyroxine (i.e. thyroid hormone) replacement dosage at end of the study' and 'economic costs'－were not assessed either. One study at high risk of bias showed a statistically significant improvement in subjective well-being with sodium selenite 200 μg plus levothyroxine compared with placebo plus levothyroxine (14/18 compared with 3/18, respectively). Selenomethionine 200 μg reduced the serum levels of anti-thyroid peroxidase antibodies in three studies, and although the changes from baseline were statistically significant, their clinical relevance is unclear. Adverse events were reported in two studies, and selenium supplementation did not lead to more adverse events than were seen with placebo. One adverse event was reported in both studies in the selenomethionine 200 μg plus LT4 arm versus none in the control arm. In conclusion, the results of these four studies do not provide enough evidence to support the use of selenium in the treatment of Hashimoto's thyroiditis.
We carried out a comprehensive search for studies. The evidence is current to December 2014. No randomised controlled trials were found that evaluated the effectiveness of sleep positioning systems to reduce or prevent hip migration. Two small randomised controlled trials compared children's quality of sleep when they were using and not using their sleep positioning system. One of these studies also examined pain when sleeping in and out of a sleep positioning system. These were cross-over trials (see Cochrane Glossary). The children in these studies spent a few nights using their sleep positioning system and then a few nights not using it, or the other way round. The order in which they either used or did not use the equipment was randomised. Twenty-one children with cerebral palsy, aged between 5 and 16 years, who were used to sleeping in sleep positioning systems took part in the studies. One of the studies took place in a sleep laboratory and the other study took place in the children's homes. Neither study reported any differences in quality of sleep or pain whether using or not using their sleep positioning system. These results need to be interpreted cautiously due to the small numbers of children involved and the fact that the children who participated were already accustomed users of the equipment. There were also various weaknesses in the way the research was designed and reported. The quality of the current evidence regarding the effectiveness of sleep positioning systems for children with cerebral palsy is very low and more robust research is needed to help families and professionals make informed decisions about whether to use this intervention.
We included 33 well-designed studies with a total of 2293 children in which ultrasound guidance was compared with another method of nerve localization (traditional landmarks techniques or nerve stimulator) for regional blockade in children. Sources of funding included a government organization (two studies), a charitable organization (two studies), and an institutional department (13 studies). Two studies declared that they received industry help (equipment loan). The source of funding was unclear for 14 studies. Ultrasound guidance for regional blockade in children may decrease the occurrence of failed block. It may also increase duration of the block and reduce pain at one hour after surgery. Ultrasound guidance may decrease the number of needle passes required to perform the block. However, because the vast majority of blocks in children are performed with the child under deep sedation or general anaesthesia, the true value of this finding might be arguable. There were no major complications in the included trials. There may be little or no difference between study groups in risks of minor complications. Altogether, whether or not these findings justify the extra cost of ultrasound guidance should probably also take into account the anaesthesiologist's expertise and local resources. The five ongoing studies may alter the conclusions of the review once published and assessed. We assessed the quality of the evidence as moderate for decreased occurrence of a failed block and improved pain scores at one hour; high for prolonged block duration; and very low for decreased number of needle passes.
We found six trials for the initial review. We have not found any more studies since then. Some studies are several decades old and not very relevant to pills available today. A newer pill containing the progestin desogestrel may work better to prevent pregnancy than an older pill with levonorgestrel. The newer pill caused more bleeding problems. Pills with levonorgestrel may be more effective than pills with other progestins that are no longer used. These studies are not adequate to tell how progestin-only pills compare to each other or to combined (two-hormone) pills. Larger studies with currently used pills are needed to answer these questions.
This review looked at the results of 38 studies. The results showed no convincing evidence that the programmes decreased relationship violence, or that they improved participants' attitudes, behaviours and skills related to relationship violence. The results showed that participants' knowledge about relationships improved slightly following the programmes. These results should be interpreted with caution, as individual studies differed in the types of participants and interventions that they used and the ways in which changes were measured. None of the studies looked at the effect of the programmes on physical and mental health. Further studies, which follow participants for a longer period of time and which look at the relationship between attitudes, knowledge, behaviour, skills and the number of times relationship violence occurs, are required to improve our understanding of how well these programmes work.
This review assessed evidence from randomized controlled trials (RCTs) on whether beta-blockers reduce deaths or other serious events when given to people undergoing surgery other than heart surgery. The findings for heart surgery are covered in another review. Background Surgery increases stress in the body, which responds by releasing the hormones adrenaline and noradrenaline. Stress from surgery can lead to death or other serious events such as heart attacks, stroke, or an irregular heartbeat. For surgery that does not involve the heart, an estimated 8% of people may have injury to their heart around the time of surgery. Beta-blockers are drugs that block the action of adrenaline and noradrenaline on the heart. Beta-blockers can slow down the heart, and reduce blood pressure, and this may reduce the risk of serious events. However, beta-blockers may lead to a very low heart rate or very low blood pressure which could increase the risk of death or a stroke. Prevention of early complications after surgery is important, but using beta-blockers to prevent these complications is controversial. Study characteristics The evidence is current to 28 June 2019. We included 83 RCTs with 14,967 adults who were undergoing different types of surgery other than heart surgery. Eighteen studies are awaiting classification (because we did not have enough details to assess them), and three studies are ongoing. The types of beta-blockers used in the studies were: propranolol, metoprolol, esmolol, landiolol, nadolol, atenolol, labetalol, oxprenolol, and pindolol. Studies compared these beta-blockers with either a placebo (disguised to look like a beta-blocker but containing no medicine) or with standard care. Key results Beta-blockers may make little or no difference to the number of people who die within 30 days of surgery (16 studies, 11,446 participants; low-certainty evidence), have a stroke (6 studies, 9460 participants; low-certainty evidence), or experience ventricular arrhythmias (irregular heartbeat rhythms, starting in the main chambers of the heart, that are potentially life-threatening and may need immediate medical treatment; 5 studies, 476 participants; very low-certainty evidence). We found that beta-blockers may reduce atrial fibrillation (an irregular heartbeat, starting in the atrial chambers of the heart, that increases the risk of stroke if untreated; 9 studies, 9080 participants; low certainty-evidence), and the number of people who have a heart attack (12 studies, 10,520 participants; low-certainty evidence). However, taking beta-blockers may increase the number of people who experience a very low heart rate (49 studies, 12,239 participants; low-certainty evidence), or very low blood pressure (49 studies, 12,304 participants; moderate-certainty evidence), around the time of surgery. In a few studies, we also found little or no difference in the number of people who died after 30 days, who died because of a heart problem, or had heart failure. We found no evidence of whether beta-blockers alter the length of time in hospital. No studies assessed whether people who were given beta-blockers had a better quality of life after heart surgery. Certainty of the evidence The certainty of the evidence in this review was limited by including some studies that were at high risk of bias, and we noticed that some of our findings were different if we only included placebo-controlled studies or studies that reported how participants were randomized. We also found one large, well-conducted, international study that had different findings to the smaller studies. It showed a reduction in heart attacks and an increase in stroke and all-cause mortality when beta-blockers were used, whilst the other studies did not show a clear effect. We were also less certain of the findings for outcomes with few studies, such as for ventricular arrhythmias. Conclusion Although beta-blockers may make little or no difference to the number of people who die within 30 days, have a stroke, or have ventricular arrhythmias, they may reduce atrial fibrillation and heart attacks. Taking beta-blockers may increase the number of people with a very low heart rate or very low blood pressure around the time of surgery. Further evidence from large, placebo-controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life.
This review identified one randomised controlled trial of donepezil in people with Down syndrome. This shows, at best, a modest, non statistically significant trend in favour of people with Down syndrome and Alzheimer's dementia who are able to tolerate donepezil. The trial was of good quality, but small. It is important to note that people with Down syndrome may often have other conditions which mean that the drug is not suitable for all. Further research is needed.
This review include 36 studies, identified from 278 references retrieved until December 2009, and report a moderate association between colorectal cancer recurrence and perioperative transfusions, with an OR of 1.42 (95% CI, 1.20 to 1.67). Similar estimates are present in several subgroup meta-analyses, as well as in meta-analyses stratified for known risk factors. These findings support carefully restricted indications for perioperative blood transfusions in colorectal cancer patients operated for cure, and continue to await the results of studies addressing the role of surgeon-related risk factors on the need for transfusion and disease recurrence.
The evidence is current to September 2017. We included four studies with 151 participants in the review. All participants were critically ill and were in the ICU. All studies compared melatonin with no agent (an inactive substance called a placebo), or with usual care. We did not combine data from the four included studies. Three studies used nurses and participants to assess sleep and reported no difference in quality and quantity of sleep. Two studies used equipment to measure quality and quantity of sleep, and one of these studies reported no difference in sleep efficiency (how well the person sleeps during night-time hours) according to melatonin use and, according to some analysis, evidence of "better sleep" for those given melatonin. One study reported problems with equipment which led to a loss of data. One study reported no difference in anxiety, and there was no difference in mortality, or length of stay in the ICU. We noted few potential side effects of melatonin (headache in one participant, and excessive sleepiness in another participant). We noted differences between groups in doses of melatonin and two studies reported differences between groups in participant characteristics which could have affected the results. One study had a large loss of data and another study did not use standard anaesthetic drugs to sedate patients. Few studies used appropriate equipment to measure quantity of sleep. We found few studies with few participants that assessed our review outcomes. We judged all evidence to be very low quality, and we could not be certain whether melatonin given to adults in the ICU improves quantity and quality of sleep. We found five ongoing studies in database and clinical trial register searches. Inclusion of these studies in future review updates would provide more certainty for the review outcomes.
We identified 16 trials involving 3578 adults that met our criteria. These studies included different types of interventions used in different places like touch screen computers in hospital clinics, computers connected to the Internet at home and programmes that communicated with mobile phones. The average age of people taking part was between 46 to 67 years old and most of those people had lived with diabetes for 6 to 13 years. Participants were given access to the interventions for 1 to 12 months, depending on the intervention. Three out of the 3578 participants died but these deaths did not appear to be linked to the trials. Overall, there is evidence that computer programmes have a small beneficial effect on blood sugar control - the estimated improvement in glycosylated haemoglobin A1c (HbA1c - a long-term measurement of metabolic control) was 2.3 mmol/mol or 0.2%. This was slightly higher when we looked at studies that used mobile phones to deliver their intervention - the estimated improvement in HbA1c was 5.5 mmol/mol or 0.5% in the studies that used mobile phones. Some of the programmes lowered cholesterol slightly. None of the programmes helped with weight loss or coping with depression. One participant withdrew because of anxiety but there were no obvious side effects and hypoglycaemic episodes were not reported in any of the studies. There was very little information about costs or value for money. In summary, existing computer programmes to help adults self-manage type 2 diabetes appear to have a small positive effect on blood sugar control and the mobile phone interventions appeared to have larger effects. There is no evidence to show that current programmes can help with weight loss, depression or improving health-related quality of life but they do appear to be safe.
We only found two small trials involving 79 patients; the results of the review suggested that anticoagulant drugs are probably safe and may be beneficial for people with sinus thrombosis but these results are not conclusive.
We searched electronic databases and abstracts for relevant studies. The search was last updated in June 2015. We found six studies, with 350 participants followed-up for at least three months. All of these studies enrolled participants undergoing knee replacement. Because the studies did not report the same outcomes, it was difficult to pool the results. We could only pool three out of six randomized controlled trials studying regional anaesthesia for better function after total knee replacement. Pooling data from 140 participants, with range of motion assessed at three months after surgery, there was no statistically significant difference between the use of regional analgesia and conventional pain control with intravenous medications. None of the included studies examined long-term adverse effects like persistent nerve damage. We deemed the quality of the evidence to be very low, as the included studies were not considered to be of high calibre and included few participants. We do not have enough information to determine if regional anaesthesia improves function after major joint replacement or not. We need more and better clinical trials to decide whether there is an effect of regional analgesia on the surgical results after total shoulder, hip or knee replacement surgery. We need more research to understand if regional analgesia increases the risk of falls after joint replacement.
We undertook this review to determine the effects of pipotiazine palmitate for schizophrenia in comparison to placebo, other oral antipsychotics and other depot antipsychotics. We included results of 12 medium term trials, two long term trials, three short term trials and one trial that looked at immediate effects. We found that depot pipotiazine is effective for the treatment of schizophrenia, but overall was similar in effect to other depots and oral typical antipsychotic drugs.
This systematic review was undertaken to see if giving folate to people with depressive disorders reduced their depressive symptoms. Three randomized trials were identified, involving a total of 247 people. In all three trials, folate was well tolerated. In two of these trials, folate was added to other antidepressant drug treatment and there was limited evidence that folate helped. In the third trial, folate was compared to trazodone, an antidepressant drug. No difference was found. There is therefore limited evidence that adding folate to other antidepressant may be helpful, but larger trials are needed before patients and clinicians can be confident that it will be helpful.
We included all randomised controlled trials that compared adjustment of asthma medications by either usual clinical care (control group) versus using exhaled nitric oxide. The participants included in the trials had asthma diagnosed as per relevant asthma guidelines. The evidence is current to June 2016 when the searches were last completed. The review included nine studies (involving 1426 children) that varied in a several ways including length of the study, exhaled nitric oxide cut-off levels used for altering medicines and the way each study defined flare-ups or attacks (called exacerbations). The studies ranged from 6 to 12 months in length. The exhaled nitric oxide cut-off values used by the different studies as a basis for decreasing or increasing medicines also varied. The mean age of the participants ranged from 10 to 14 years old. In this review, we found that guiding asthma medicines based on exhaled nitric oxide (compared to a control group) was beneficial in reducing the number of children who had at least one exacerbation during the study. In the control group where therapy was guided according to clinical symptoms, 40 children out of 100 had at least one exacerbation over 48.5 weeks, compared to 28 out of 100 children where treatment was guided by exhaled nitric oxide. However, we found no difference between groups in other measures of asthma severity that impact on day-to-day clinical symptoms or inhaled corticosteroid dose (medications used to control asthma). Therefore, using exhaled nitric oxide levels to adjust asthma therapy may reduce the number of attacks that children with asthma have but does not impact on the day-to-day symptoms. The level of evidence found ranged from moderate, when comparing the two groups for the number of children who had one or more exacerbations, to very low when comparing the number of exacerbations.
The evidence is current to April 2015. In this update, 12 trials were identified that compared giving granulocyte transfusions to prevent infections compared to not giving granulocytes to prevent infection. One trial has not yet been completed. Eleven trials containing a total of 653 participants were reviewed. These trials were conducted between 1978 and 2006. Data from one trial were not included in the analyses because patients were included within the trial more than once. Ten studies included only adults, and two studies included children and adults. Six studies reported their funding sources, and all were funded by charities or governments. Giving granulocyte transfusions to prevent infections did not affect the risk of death due to infection, or the risk of death due to any cause. Giving granulocyte transfusions to prevent infections decreased the number of people who had a bacterial or fungal infection in the blood, but did not decrease the number of people having a localised bacterial or fungal infection. It is unknown whether granulocyte transfusions increased the risk of having a serious adverse event because adverse events were only reported in people receiving granulocyte transfusions. The evidence for most of the findings was of very low or low quality. This was because patients and their doctors knew which study arm the patient had been allocated to and two of the studies were not true randomised studies (patients were allocated to the granulocyte transfusion arm if they had a suitable granulocyte donor).
This review examined five randomised trials with five different Chinese herbal medicines, involving a total of 664 participants. All trials were conducted and published in China. None of the trials mentioned adverse effects. The methodological limitations in these studies are quite obvious, and any conclusions based on their results should be made with caution. This systematic review did not find sufficient evidence to support the objective efficacy and safety of TCM for adhesive SBO patients. Further high-quality trials evaluating oral TCM for adhesive SBO are urgently needed.
Until 4 August 2016, we did computer searches for studies of a POC compared with another birth control method or no contraceptive. For the initial review, we wrote to investigators to find other trials. The focus was on change in body weight or other body measure of lean or fat mass.  With six new studies in this update, we have 22 studies that included 11,450 women. The groups compared did not differ much for weight change or other body measures in 15 studies. Five studies with moderate or low quality results showed a difference between study groups. Three studies showed differences for users of the injectable ‘depo’ versus no hormonal method. Depo users had a greater weight gain in two studies. In the third study, adolescents had a greater increase in body fat (%) and decrease in lean body mass (%). Two studies showed a greater increase in body fat (%) for users of hormonal intrauterine contraception versus women not using a hormonal method. One also showed a similar difference with a progestin-only pill. Both studies showed a greater decrease in lean body mass with POC use.  We found little evidence of weight gain when using POCs. Mean weight gain at 6 or 12 months was less than 2 kg (4.4 lb) for most studies. The groups using other birth control methods had about the same weight gain. Good counseling about typical weight gain may help women continue using birth control.
In adults, low-quality evidence shows greater benefit from psychological therapies than from control comparators in reducing (symptoms of) PTSD, major depression, and anxiety disorders. This evidence supports the approach of providing psychological therapies to populations affected by humanitarian crises, although we identified no studies that looked at the effectiveness or acceptability of psychological therapies for depressive and anxiety symptoms beyond six months. Only a small proportion of included trials reported data on children and adolescents, which provided very low-quality evidence of greater benefit derived from psychological treatments. With regard to acceptability, moderate- to low-quality evidence suggests no differences in dropout rates among adults and children and adolescents. Reviewers found no studies evaluating psychological treatments for (symptoms of) somatoform disorders or medically unexplained physical symptoms (MUPS) in adults, nor in children or adolescents, respectively. Researchers should conduct higher-quality trials to further evaluate the effectiveness of psychological therapies provided over longer periods to adults and to children and adolescents. Ideally, trials should be randomised, should use culturally appropriate and validated instruments to evaluate outcomes, and should assess correlates of reductions in treatment effects over time; in addition, researchers should make every effort to ensure high rates of follow-up beyond six months after completion of therapy.
Despite the evidence accumulated from biological and epidemiological (observational) studies and non-randomised clinical trials, only one randomised, controlled trial could be included in this review. This study had 44 participants. Participants who were given a single glucose drink showed possible momentary enhancement of cognitive performance compared to those given a saccharin drink. A safety assessment was not reported. We need more studies on different types of carbohydrates, particularly those from fruit, vegetable and whole grain sources, for older adults with normal cognition and mild cognitive impairment to understand the role of this nutrient type in the prevention or reduction of cognitive decline.
The evidence was current as of June 2015. We identified six RCTs, which had enrolled 1088 patients. The studies took quite different approaches to their investigations, and we found only one study that had explored the duration of antibiotic therapy for ICU patients who had HAP, but were not mechanically ventilated. For patients with VAP, our main finding was that a course of seven or eight days of antibiotics was associated with an overall decrease in antibiotic administration and reduced the recurrence of pneumonia due to resistant organisms when compared with a 10- to 15-day course. Furthermore, this was achieved without any significant effect on mortality. Nevertheless, in cases when VAP was due to a particular type of organism ('non-fermenting Gram-negative bacillus'), which can be difficult to eradicate with antibiotics, the risk of pneumonia recurring appeared higher after a short course of treatment. One study found that for patients with possible (but low probability) HAP a short (three-day) course of therapy seemed to be associated with a lower chance of acquiring resistant organisms or of subsequent infections being due to a resistant organism. The quality of evidence for the main outcome measures was low to moderate. The main reasons that the quality was not high were that only a small number of studies were identified, and that there were differences in patient populations, in the nature of the interventions between studies and in the reported outcomes.
At least one dose of MMR vaccine is effective in preventing clinical mumps among children and adolescents when prepared with Jeryl Lynn strains (vaccine effectiveness = 69% to 81%, one cohort and one case-control study, 1656 participants), as well as when prepared with Urabe strain (vaccine effectiveness = 70% to 75%, one cohort and one case-control study, 1964 participants). Effectiveness against laboratory-confirmed mumps in children and adolescents was estimated to be between 64% to 66% for one and 83% to 88% for two doses of Jeryl Lynn MMR (two case-control studies, 1664 participants) and 87% for Urabe-containing MMR (one cohort study, 48 participants). Vaccination with Urabe MMR confers protection against secondary mumps infection (vaccine effectiveness = 73%, one cohort study, 147 participants). We identified no studies assessing the effectiveness of MMR vaccine against clinical or laboratory-confirmed rubella. Results from two very large case series studies involving about 1,500,000 children who were given the MMR vaccine containing Urabe or Leningrad-Zagreb strains show this vaccine to be associated with aseptic meningitis; whereas administration of the vaccine containing Moraten, Jeryl Lynn, Wistar RA, RIT 4385 strains is associated with febrile convulsion in children aged below five years (one person-time cohort study, 537,171 participants; two self controlled case series studies, 1001 participants). The MMR vaccine could also be associated with idiopathic thrombocytopaenic purpura (two case-controls, 2450 participants, one self controlled case series, 63 participants). We could assess no significant association between MMR immunisation and the following conditions: autism, asthma, leukaemia, hay fever, type 1 diabetes, gait disturbance, Crohn's disease, demyelinating diseases, or bacterial or viral infections. The methodological quality of many of the included studies made it difficult to generalise their results. The glossary of study designs is available in the full-text review.
The evidence is current to April 2016. We identified 11 randomised controlled trials, of which seven had been completed. Of the seven completed trials, five trials (456 participants) assessed TPO mimetics, one trial (eight participants) assessed tranexamic acid and one trial (eight participants) assessed DDAVP. The trial of DDAVP only assessed the bleeding time: the time taken for bleeding to stop after a small cut is made in the participant's forearm. It did not assess any of the outcomes of interest to this review. The trial of tranexamic acid had significant methodological flaws in the way bleeding was reported. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified. Consequently, quantitative analysis was only performed on the five trials assessing TPO mimetics. Four of these trials included adults with myelodysplastic syndrome (MDS) and one trial assessed adults with MDS or acute myeloid leukaemia (AML). We assessed all five trials of TPO mimetics included in this review to be at high risk as the manufacturers if the TPO mimetics were directly involved in the design and publication of the trials. Differences in severity of disease and number of participants undergoing chemotherapy between trials meant that network meta-analysis could not be performed. A requirement of network meta-analysis is that participants in each trial should meet the eligibility criteria for each trial that is included. The four ongoing trials are all comparing TPO mimetics versus placebo; they are expected to recruit 837 participants in total and are due to be completed by December 2020. TPO mimetics may make little or no difference to the number of participants with any bleeding or severe/life-threatening bleeding. We are very uncertain whether TPO mimetics reduce the risk of mortality. TPO mimetics probably reduce the number of participants who need a platelet transfusion. We are very uncertain whether TPO mimetics reduce the risk of transfusion reactions or risk of thromboembolism. TPO mimetics may have little or no effect on the risk of drug reactions. No trial reported the number of days bleeding per participant, platelet transfusion episodes, mean red cell transfusions per participant, red cell transfusion episodes, transfusion-transmitted infections, formation of antiplatelet antibodies or platelet refractoriness. The quality of the evidence was low or very low for all outcomes except the number of participants receiving a platelet transfusion which was moderate-quality evidence.
We identified 68 randomised controlled trials comparing various treatments for impetigo. Altogether, these studies evaluated 26 oral treatments and 24 topical treatments, including placebo, and results were described for 5708 participants. Overall, topical antibiotics showed better cure rates than topical placebo. Two antibiotic creams, mupirocin and fusidic acid, are at least as effective as oral antibiotics where the disease is not extensive. There was no clear evidence that either of these most commonly studied topical antibiotics was more effective than the other. Topical mupirocin was superior to the oral antibiotic, oral erythromycin. We found that the oral antibiotic, oral penicillin, is not effective for impetigo, while other oral antibiotics (e.g. erythromycin and cloxacillin) can help. It is unclear if oral antibiotics are superior to topical antibiotics for people with extensive impetigo. There is a lack of evidence to suggest that using disinfectant solutions improves impetigo. When 2 studies with 292 participants were pooled, topical antibiotics were significantly better than disinfecting treatments. Reported side-effects for topical treatments were mild and low in frequency; the treatments sometimes resulted in itching, burning, or staining. Oral antibiotics produced gastrointestinal complaints, such as nausea and diarrhoea, in 2% to 30% of participants, depending upon the specific antibiotic. Worldwide, bacteria causing impetigo show growing resistance rates for commonly used antibiotics. For a newly developed topical treatment, retapamulin, no resistance has yet been reported.
We did computer searches to find studies that compared any operation to any medicine used for abortion at this stage of pregnancy. We wrote to researchers and looked through book chapters and other articles to find more studies. We found two studies. The first compared dilation and evacuation (D&E) to injecting a drug into the pregnant womb. The second compared D&E to drugs taken by mouth and by vagina. The D&E operation was better than injecting medicines into the womb. Medicines taken by mouth and vagina worked as well and were as acceptable as a D&E, but caused more pain and side effects. More studies with modern medicines used for abortion after 3 months of pregnancy are needed.
This Cochrane review included 11 randomised controlled trials, in which women were randomly allocated to receive seminal plasma or not. These trials included a total of 3215 women undergoing ART. The evidence is current to October 2017. We found no clear evidence to suggest whether seminal plasma application influences rates of live birth or miscarriage in women undergoing ART. However, we found low-quality evidence suggesting that seminal plasma application may possibly lead to more clinical pregnancies than standard ART. There was low-quality evidence suggesting little or no difference between the groups in rates of multiple pregnancy. There was insufficient evidence to reach any conclusions about the risk of ectopic pregnancy (pregnancy in which the embryo attaches outside the womb), and no data were available on infectious complications or other adverse events. We conclude that seminal plasma application is worth further investigation focusing on live birth and miscarriage rates. The quality of evidence ranged from very low to low.The main limitations were risk of bias (associated with poor reporting of study methods) and lack of data for the primary outcome of live birth rate.
Spermicides have been used as birth control for thousands of years. Studies have recently looked at how well they work to prevent pregnancy and whether women like them. Spermicides contain an active ingredient (usually nonoxynol-9) and something to disperse the product, such as foam or vaginal suppository (pessary). This review compared how well different spermicides worked for birth control when used alone. In August 2013, we did computer searches for randomized trials of spermicides used for birth control. We have not found any new trials since the initial review. For the initial review, we also wrote to researchers to find other trials. Trials had to focus on a spermicide used alone for birth control. The product could be compared to a different spermicide, the same spermicide used with a barrier method, another dose of the same spermicide, a different base for the same product, or another type of birth control. Each study must have had data on pregnancy. We located reports from 14 trials for the initial review. We have not found any new trials since then. The largest trial compared five different spermicides. The gel with the smallest amount of nonoxynol-9 did not prevent pregnancy as well as products with more of the same ingredient. Women liked the gel better than the film or suppository. Few differences were found in the other studies. These trials had problems recruiting women into the studies and then keeping them until the trial ended. Large losses to follow up can bias the results.
The review authors searched the medical literature up to 3 March 2015, and identified 28 relevant medical trials, with a total of 2365 participants. The trials were performed in ten different countries, generally in out-patient settings. All the trials had low numbers of participants, which makes potential overestimation of benefits and underestimation of harms more likely. Half of the trials were sponsored by the pharmaceutical industry that produces these growth factors. The trials tested 11 different types of growth factor, usually by applying them to the ulcer surface. Growth factors had no effect on the risk of having one toe or more amputated when compared with either another growth factor, or placebo (inactive fake medicine), or standard care alone (evidence from four trials). However, when compared with placebo or no growth factor, growth factors seemed to make complete healing of ulcers (wound closure) more likely to occur (evidence from 12 trials). None of the trials reported data on participants’ quality of life. Harms caused by treatments were poorly reported, so the safety profile of growth factors remains unclear. It is clear that more trials are required to assess the benefits and harms of growth factors in the treatment of diabetic foot ulcers. These trials should be well-designed, conducted by independent researchers (not industry-sponsored), and have large numbers of participants. They should report outcomes that are of interest to patients, such as: how many of the participants’ ulcers healed, and how long the healing took; any level of amputation in the foot; quality of life; ulcer-free days following treatment; and harms caused by treatment, including whether there are any potential cancer risks.
We identified 10 studies reporting information on 5056 people with abdominal pain that started suddenly. The studies included pancreatitis due to all causes. All of the studies were of unclear or low methodological quality, which may result in arriving at false conclusions. We excluded the study that contributed approximately two-thirds of the participants included in this review from the results of the analysis presented below due to concerns about whether the participants included in the study are typical of those seen in the emergency department. The accuracy of serum amylase, serum lipase, and urinary trypsinogen-2 in making the diagnosis of acute pancreatitis was similar. About a quarter of people with acute pancreatitis fail to be diagnosed as having acute pancreatitis with these tests. The patient should be admitted and treated as having acute pancreatitis, even if these tests are normal, if there is a suspicion of acute pancreatitis. As about 1 in 10 patients without acute pancreatitis may be wrongly diagnosed as having acute pancreatitis with these tests, it is important to consider other conditions that require urgent surgery, even if these tests are abnormal. The diagnostic performance of these tests decreases even further with the progression of time, and additional investigations should be performed if there is a suspicion of acute pancreatitis.
We considered only studies in which chance decided whether men with prostate cancer got early or late hormonal treatment. We found 10 studies that matched our question. We found that early hormonal treatment probably lowers the risk of dying from any cause. The risk of serious unwanted effects may be similar to that of late treatment. Early hormonal treatment probably lowers the risk of dying from prostate cancer and slightly lowers the risk of problems related to cancer spreading to the bones. Men getting early treatment may be more likely to feel tired and develop heart weakness. Overall quality of life is probably unaffected (or only slightly affected) by early treatment. The certainty of evidence was either moderate, which means that the true results are likely close to what we found; or low, in which case our concern is that the true results could be quite different to what we found.
The review of trials found that dual chamber pacemakers tended to prevent more subsequent heart problems than single chamber ventricular pacemakers. The impact on people's overall quality of life is uncertain. The review did not investigate the relative benefits or risks of surgery to upgrade to a dual chamber pacemaker.
Five studies comparing vitamins C and E versus placebo (no vitamins C and E) in 214 people with asthma or exercise-induced breathlessness were included in this review. Four studies included adults, and one included children. The very limited number of studies available for review and their different designs meant that we were only able to describe individual studies, rather than pooling their results to determine an average result. In most study reports, the design was not well described; therefore it was impossible to assess the risk of bias for most of the studies. In terms of our key outcomes, very few relevant data were provided by the trial authors. We found no indication of benefit in the studies that considered vitamins C and E in relation to asthma. However, at this stage, it is not possible to form any clear conclusions based on these findings, as available evidence is insufficient to allow proper assessment of the use of vitamins C and E as treatment for patients with asthma. Additional well-designed research is required to answer this question. How patients were allocated to receive either vitamins C and E or placebo was not clearly described in any of the five included studies. This may mean that the studies were not well randomised, which can affect the results. A second concern is that the designs of the studies were different, which means that we cannot be certain that the studies were measuring the same thing. By taking this into account, we judged the evidence in this review overall to be of low to moderate quality.
The evidence is current to May 2013. Ten studies were included: four studies used manual lymph drainage with usual care, or combined with exercise or compression versus usual care or education alone (395 participants); three studies examined early versus late start of postoperative shoulder exercises (378 people); two studies used either progressive resistance exercise or restricted activity (358 people); and one study investigated a physiotherapy care plan versus no physiotherapy (65 people). The duration of patient follow-up ranged from two days to two years after the intervention. No firm conclusion can be drawn about the effect of manual lymph drainage in addition to exercise and education on preventing the incidence of lymphoedema. This is because the two included studies found contradicting results. In addition, no firm conclusion can be drawn about manual lymph drainage in combination with other interventions, because only two studies were found that each tested different combinations. One of these studies found that manual lymph drainage combined with exercise lowered the risk of lymphoedema. The other study combined manual lymph drainage with compression, but this study was too small to draw conclusions. Arm mobility (i.e. reaching upwards over the head) was better after manual lymph drainage than without it, but this improvement lasted only for the first few weeks after breast cancer surgery. When assessing whether early or late shoulder exercises reduced the likelihood of developing lymphoedema, the studies did not provide a clear result. The likely incidence of lymphoedema ranged from 5% to 27% (early start) compared to 4% to 20% (for delayed start) during the first 6 to 12 months after surgery. Starting shoulder exercises immediately after surgery may improve shoulder mobility in the first month, compared to starting after the first week but no firm conclusions can be drawn and mobility is comparable later on. Progressive resistance training did not increase the risk of developing lymphoedema compared to restricted activity, on the basis that symptoms were monitored and treated immediately if they occurred. For all investigated interventions, no firm conclusion can be drawn about their effectiveness in reducing pain or improving quality of life. The evidence was considered to be low quality, except for the evidence on resistance training, which was of moderate quality. This was because many studies had shortcomings in how they were conducted; there were only a small number of studies for each intervention; the results differed between comparable studies; and the groups studied were relatively small.
We found 18 trials in 141,807 participants to answer the question. All-cause mortality was not different between CCBs and any other antihypertensive drug classes. Diuretics were found to be better at reducing total cardiovascular events than CCBs and CCBs were found to be better at reducing total cardiovascular events than β-blockers. This information will be helpful for health professionals and patients to assist them in choosing the best drug for initial treatment of hypertension.
We searched for all the trial evidence from trials of three to 12 week duration reporting the effect of rosuvastatin on cholesterol. We found 108 trials involving 19,596 participants. Based on an informal comparison with atorvastatin three-fold lower doses of rosuvastatin are needed to lower cholesterol by the same amount. This review cannot be used to assess harms of rosuvastatin, because of the short duration of these trials and the high risk of bias for this outcome; adverse effects were only reported in 10 of the 18 trials that could be used to assess harms.
From the four randomised controlled trials involving 644 pregnant women that we included in this review, results indicate that a higher dose of oxytocin (4-7 mU per minute, compared with 1-2 mU per minute) reduced the length of labour and the rate of caesarean sections with increased spontaneous vaginal births, but the studies did not provide enough evidence on possible differences between the high- and low-dose regimens on adverse events including hyperstimulation of the uterus, and outcomes for the newborn infant. Only one trial reported on the possible effect on women. The overall quality of the included trials was mixed, but this might reflect how clinical trials were reported in the past. While the current evidence is promising and suggests that the high-dose regimens reduce the length of labour and the rate of caesarean sections, this evidence is not strong enough to recommend that high-dose regimens are used routinely for women delayed in labour. We recommend that further research is carried out.
This review set out to compare both techniques. Our literature search has shown that a well-designed randomised trial comparing surgery and radiosurgery for patients with solitary brain metastasis has never been performed. Therefore, this review has been unable to show any advantage of one treatment over the other for this group of patients.
We identified five randomised clinical studies with 1601 children comparing two dosing schedules. Participants were aged 12 years or younger with AOM. The primary outcome was clinical cure rate in terms of resolution of otalgia and fever at the end of antibiotic therapy (days seven to 15). The secondary outcomes were clinical cure rate in terms of middle ear effusion during therapy, clinical cure rate post-treatment (one to three months) in terms of resolution of middle ear infection, AOM complications and adverse events to medication. The results showed that treating acute middle ear infection with either once/twice daily or three times daily amoxicillin, with or without clavulanate, has the same results using our outcome measures, including adverse events such as diarrhoea and skin reactions. The evidence is current to March 2013.
Although early cord clamping has been thought to reduce the risk of bleeding after birth (postpartum haemorrhage), this review of 15 randomised trials involving a total of 3911 women and infant pairs showed no significant difference in postpartum haemorrhage rates when early and late cord clamping (generally between one and three minutes) were compared. There were, however, some potentially important advantages of delayed cord clamping in healthy term infants, such as higher birthweight, early haemoglobin concentration, and increased iron reserves up to six months after birth. These need to be balanced against a small additional risk of jaundice in newborns that requires phototherapy.
We searched for relevant studies that had been conducted up until January 2016 and identified nine trials involving a total of 3253 nursing home residents. The average age of residents across the studies ranged from 78 to 86 years. In all of the studies most of the people taking part had dentures (between 62% and 87%). The trials evaluated a variety of approaches including educational programmes, skills training, and written information material. Topics included dental issues that were particularly relevant for older people such as care of dentures and covered dental and oral diseases, prevention of oral diseases, dental hygiene tools, and oral health care guidelines. The length of the trials ranged from three months to five years. We could not identify a clear benefit of training of nurses and/or residents on residents' dental health as assessed by dental and denture plaque. No study assessed oral health, oral health-related quality of life or adverse events. As education programmes were not fully described, results do not allow for clear conclusions about the effectiveness or potential harm of specific oral health education interventions in nursing homes. Overall, there was a low quality of information from the studies regarding all of the results. We conclude that there is a need for clinical trials to investigate the advantages and harms of oral health educational programmes in nursing homes.
We identified five studies. Two of these were concerned with diet advice given concerning general health (one was about alcohol and one was about fruit and vegetable consumption). In both these studies there was a change to healthier behaviour following the advice. We also identified three studies which attempted to change sugar consumption habits in order to reduce dental decay. However, in two out of these three studies there were also other types and forms of advice given at the same time, for example about toothbrushing. It was therefore impossible to say whether changes in diet came about because of the diet advice given or because they were subtly influenced by the other messages. For example: advice on toothbrushing might make patients more aware of their oral health resulting in changes to their diet. Most of the studies concerning sugar consumption are of relatively weak quality. The evidence for dietary advice aiming to change sugar consumption is poor. Further studies in this area should be considered.
We systematically searched various medical databases to determine how the piggy-back method compares with the standard method of liver transplantation or with different piggy-back techniques. Two clinical trials randomised 106 patients to the piggy-back method (53 patients) versus the standard method (53 patients). Both trials were at high risk of systematic errors. There was no significant difference in post-operative death, primary graft non-function (the liver graft does not start functioning at all), complications related to the blood vessels, kidney failure, blood transfusion requirements, intensive therapy unit (ITU) stay, or hospital stay between the two groups. The proportion of patients who developed chest complications were significantly higher with the piggy-back method than with the conventional method (76% in piggy-back method versus 44% in conventional method; statistically significant). One trial randomised 80 patients to a variant of piggy-back (in which blood from the intestines is temporarily diverted; 40 patients) versus standard piggy-back method (in which blood from the intestines is blocked; 40 patients). This trial was at high risk of systematic error. There was no significant difference in post-operative death, re-transplantation due to primary graft non-function (liver graft does not start functioning at all), vascular complications, kidney failure, or hospital stay between the two groups. Significantly fewer patients required blood transfusion with the variant piggy-back method (55%) than with the standard piggy-back method (75%). The ITU stay was significantly shorter in the variant (2.9 days) than with the standard piggy-back method (4.9 days). There were no trials comparing piggy-back method and standard method of liver transplantation without diversion of venous blood or different techniques of piggy-back method. We conclude that there is currently no evidence to recommend or refute the use of piggy-back method of liver transplantation.
These results were obtained from short-term randomised controlled trials. However, it should be noted that information that is not reported in this review, from longer-term follow-up studies of people using vigabatrin, has shown that its use is frequently associated with visual field defects which may go undetected.
The review of trials found no evidence that growth hormone helps improve birth rates in women who are undergoing ovulation induction prior to in-vitro fertilisation. However there is some evidence of increased pregnancy and birth rates in women who are considered 'poor responders' to in-vitro fertilisation. More research is needed.
Fifty-five studies provided information for the review. Thirty-four studies compared H. pylori eradication therapy plus ulcer-healing drug against ulcer-healing drug alone in the healing of duodenal ulcer. Two studies compared H. pylori eradication therapy against no treatment in the healing of duodenal ulcer. Fifteen studies compared H. pylori eradication therapy plus ulcer-healing drug against ulcer-healing drug alone in the healing of gastric ulcer. Three studies compared H. pylori eradication therapy plus ulcer-healing drug against ulcer-healing drug alone in the healing of peptic ulcer (gastric or duodenal ulcer). One study compared H. pylori eradication therapy against no treatment in the healing of peptic ulcer (gastric or duodenal ulcer). Four studies compared H. pylori eradication therapy against ulcer-healing drug in preventing the recurrence of duodenal ulcer after initial ulcer had been healed. Twenty-seven studies compared H. pylori eradication therapy against no treatment in preventing the recurrence of duodenal ulcer after initial ulcer had been healed. Twelve studies compared H. pylori eradication therapy against no treatment in preventing the recurrence of gastric ulcer after initial ulcer had been healed, while one study compared H. pylori eradication therapy against no treatment in preventing the recurrence of peptic ulcer (gastric or duodenal ulcer) after initial ulcer had been healed. Four studies compared H. pylori eradication therapy plus ulcer-healing drug versus comparison regimen in the relief of symptoms from peptic ulcer (gastric or duodenal ulcer). There were no studies comparing H. pylori eradication therapy against no treatment in the healing of gastric ulcer, H. pylori eradication therapy against ulcer-healing drug as maintenance therapy in preventing the recurrence of gastric ulcer after initial ulcer had been healed, or H. pylori eradication therapy plus ulcer-healing drug against no treatment or ulcer-healing drug in the relief of symptoms in people with peptic ulcer. Some trials provided information for more than one comparison. The evidence is current until March 2016. Adding a one to two-week course of H. pylori eradication therapy speeds up ulcer healing for people with H. pylori-positive duodenal ulcer when compared to ulcer-healing drugs alone and no treatment. H. pylori eradication therapy is also effective in preventing recurrence of duodenal and gastric ulcer (ulcer returning after initial healing) compared to no treatment. There is currently no evidence that H. pylori eradication therapy is an effective treatment in people with gastric ulcer or that it is effective in preventing recurrence of duodenal ulcer compared to ulcer-healing drugs. However, because of the small number of studies included for the last two comparisons, significant benefits or harms of H. pylori eradication therapy in acute ulcer healing of gastric ulcers compared to no treatment and in preventing recurrence of duodenal ulcers compared to ulcer healing drugs cannot be ruled out. The quality of evidence was low or very low because most of the studies had errors in study design. As a result, there is a lot of uncertainty regarding the results.
In our review we found six studies, with a total of 449 patients, in which one of two interventions were applied. One intervention (four studies, 267 patients) was a CL following a consultation between the patient and the psychiatrist; the other (two studies, 182 patients) was a CL following a joint consultation between patient, psychiatrist and primary care physician. In each case comparison was against care as usual, provided by the primary care physician. The first intervention resulted in reduced medical costs (three studies) and improved physical functioning (three studies). We found evidence for a slight reduction in the severity of the MUPS, reduced medical consumption and improved social functioning following the second intervention, although in only one of two studies assessed. There are serious limitations in generalizability of the results to modern healthcare: most trials reported doctor-related outcomes with patient-related outcomes varying in results; the intervention appears to be far more effective for the most serious but rare disorders, and less so in the more common forms of MUPS; five of the six studies were performed in the United States and four studies before 1995. Furthermore the studied populations were small and five of the six studies were of moderate quality. Our final conclusion is that CLs may be helpful for physicians who treat patients with MUPS (based on the provider-related outcomes). However, until further studies are conducted to find out if the intervention results in improved patient-related outcomes, the overall effectiveness of CLs cannot be demonstrated.
We identified six randomized controlled trails with 656 participants. Five studies (620 participants) enrolled people with knee osteoarthritis, and one study (36 participants) enrolled people with knee or hip osteoarthritis. The studies included more women (70%) than men. On a scale of 0 to 20 points (lower scores mean reduced pain), people who completed a high-intensity exercise program rated their pain 0.84 points lower (4% absolute improvement) than people who completed a low-intensity exercise program. People who performed a low-intensity exercise program rated their pain at 6.6 points. On a scale of 0 to 68 points (lower scores mean better function), people who completed a high-intensity exercise program rated their physical function 2.65 points lower (4% absolute improvement) than people who completed a low-intensity exercise program. People who performed a low-intensity exercise program rated their pain at 20.4 points. On a scale of 0 to 200 mm visual analog scale (higher score means better function), people who completed a high-intensity exercise program rated their quality of life 4.3 mm higher (6.5 mm lower to 15.2 mm higher) (2% absolute improvement) than people who performed a low-intensity exercise program. People who performed a low-intensity exercise program rated their quality of life at 66.7 mm. Two per cent more people had adverse effects with high-intensity exercise, or 17 more people out of 1000. • 39 out of 1000 people reported an adverse effect related to high-intensity exercise program • 22 out of 1000 people reported an adverse effect related to low-intensity exercise program Adverse events were not systematically monitored and and were incompletely reported by group. None of the included studies reported serious adverse events. Based on the evidence, people with knee osteoarthritis who perform high-intensity exercise may experience slight improvements in knee pain and function at the end of the exercise program (8 to 24 weeks) when compared with a low-intensity exercise program. We are uncertain as to whether high-intensity exercise improves quality of life or increases the number of people who experience adverse events. We graded the quality of evidence as low for pain and function and very low for quality of life. The small number of studies and participants included in some analyses reduced the robustness and precision of these findings. Adverse effects were poorly recorded. Very low quality evidence shows we are uncertain whether higher-intensity exercise programs may result in more side effects than lower-intensity exercise programs. Further research may change the result.
We examined the research published to 12 July 2016. We included studies of oxygen therapy versus air delivered through nasal prongs or mask during exertion, continuously, 'as needed' over a defined period or as short-burst oxygen before exertion. Study participants were 18 years of age or older, had received a diagnosis of COPD, had low oxygen levels in the blood and did not receive long-term oxygen therapy. We included a total of 44 studies (1195 participants) in this review. Compared with the previous review, which was published in 2011, we have added 14 studies (493 participants) to this review. We found that oxygen can modestly reduce breathlessness. To be effective, oxygen has to be given during exercise. Most studies evaluated oxygen given during exercise testing in the laboratory. Oxygen therapy during daily life had uncertain effects on breathlessness and did not clearly change patient quality of life. We rated the quality of evidence using one of the following grades: very low, low, moderate or high. For very low-quality evidence, we were uncertain about the results. With high-quality evidence, we were very certain about the results. We found that evidence for oxygen given for breathlessness was moderate to low. We are moderately confident that oxygen can relieve breathlessness when given during exercise to people with COPD with mildly or moderately decreased blood oxygen levels. However, most studies reported acute effects during an exercise test, and no evidence suggests that oxygen decreases breathlessness during daily life. Findings indicate that oxygen does not affect health-related quality of life.
We searched the literature in October 2018. We included two studies with a total of 57 adult smokers - both men and women - with rheumatoid arthritis. One of the studies tested an intervention to help people with rheumatoid arthritis to quit smoking. This study recruited only smokers and compared this specialist, stop smoking programme with a standard, less intensive stop smoking programme. The other study tested an intervention to reduce the risk of heart disease and stroke in people with rheumatoid arthritis. Researchers recruited non-smokers and smokers and compared this programme to a brief factual information leaflet about risks of heart disease. Both studies followed study participants for six months. These studies were funded by Arthritis Research UK Educational Research Fellowship, Arthritis Research UK, the New Zealand Health Research Council, Arthritis New Zealand, and the University of Otago Research Fund. Neither of the two included studies found that the more intensive, specialist interventions aimed at people with rheumatoid arthritis helped more people with rheumatoid arthritis to quit smoking than the less intensive, generic interventions. Only one of the studies reported on the safety of the stop smoking programme used. Very few side effects related to use of nicotine replacement therapy were reported, and none of these were serious. As a result, we do not know whether helping people with inflammatory arthritis improves their disease. We rated the overall quality of the included studies as very low because studies were very few and included few participants; only one of the studies tested an intervention that specifically tried to help people to quit smoking, and there is a chance that people who received the intensive intervention were more likely to incorrectly report that they had stopped smoking when in fact they had not. As a result, further large studies should be carried out to test stop smoking programmes for people with IJD. Researchers should ensure that they measure whether people's IJD symptoms improve, and should confirm whether people have stopped smoking.
We found 14 studies up to April 2016 involving 1863 participants that looked at the benefits of these programmes for people with stroke. They were conducted in a variety of countries in a variety of formats - sometimes in groups, sometimes individually, and for varying time periods. We found that such programmes may improve the quality of life after stroke. People with stroke reported improvements in their ability to live the way they wanted and that they felt more empowered to take charge of their lives, rather than be dependent on other people for their happiness and satisfaction with life. There were no reports of any risks or negative effects. The majority of the studies were well conducted and represent credible evidence that self management programmes may benefit people with stroke who are living in the community.
We included nine randomised controlled trials involving 2391 women and their babies in this review. The trials were of moderate quality overall. All trials compared giving women a high dose versus a low dose of oxytocin for induction of labour. We found that women who had a high dose of oxytocin were not more likely to have a shorter induction to delivery interval or have a vaginal birth within 24 hours of receiving the treatment than women receiving a low dose of oxytocin. When poor-quality trials are removed from analysis however, the induction to delivery interval was significantly shorter with high-dose oxytocin compared to low-dose oxytocin. The likelihood of having a caesarean was similar with the different doses of oxytocin for induction of labour. No differences were shown between the two groups of women in terms of serious complications, including death of the mother or her baby but women receiving the high-dose oxytocin did have an increased risk of excessive uterine contractions (known as uterine hyperstimulation). No trials provided any information about the number of women with uterine hyperstimulation with changes in the babies' heart rate. Similarly, no trials assessed satisfaction of the mother or her caregivers. The trials were at moderate to high risk of bias overall. The definition of high- and low-dose protocols and the outcomes measured varied considerably across the trials. The current evidence is not strong enough to recommend high-dose over low-dose regimens for routine induction of labour. We recommend that further research is carried out.
We searched several medical databases and identified two randomised controlled trials (RCT) that met our inclusion criteria; no new trials were identified for this review update. One trial included 40 breast cancer patients receiving high-dose chemotherapy. Eighteen patients received G-CSF and 22 got antibiotics (ciprofloxacin and amphotericin) to prevent infection. Another trial evaluated GM-CSF versus antibiotics in patients with small-cell lung cancer, with 78 patients in the GM-CSF arm and 77 patients in the antibiotics arm. The study that analysed G-CSF versus antibiotics did not report all cause mortality, microbiologically or clinically documented infections, severe infections, quality of life, or adverse events. We found no evidence of a difference between the two prophylactic options for the outcomes of infection-related mortality (no patient died because of infection), or febrile neutropenia. The trial that assessed GM-CSF versus antibiotics did not found any evidence of a difference in all cause mortality, trial mortality, infections, or severe infections. The only difference between the two arms was found for the adverse event thrombocytopenia, favouring patients receiving antibiotics. Quality of life was not reported in this trial. More research is needed to determine the best prevention against infection in cancer patients. The quality of the evidence for infection-related mortality and frequency of febrile neutropenia in the G-CSF trial was very low, because of the small number of patients that were evaluated, and the study design (high risk of bias). The trial that analysed GM-CSF versus antibiotics reported overall survival, toxic deaths, infections, severe infections, and adverse events. Because of the very small number of patients included, we judged that the overall quality for all these outcomes was low. The evidence is current to December 2015.
The Information Specialist of Cochrane Schizophrenia searched their specialised register for relevant trials up to February 2017. We found sixteen trials that could be included. These trials randomised 919 adults with schizophrenia to receive either an NRI, a placebo (dummy treatment), or an antidepressant. All participants continued to receive the antipsychotic medications they were already taking. Most trials included participants who were in hospital and who had had symptoms of schizophrenia for a long time. Our main areas of interest were the effect NRIs have on improving mental and global state, cognitive functioning and quality of life for people with schizophrenia; and if NRIs cause unpleasant side-effects such as nausea. We found that compared to placebo treatment, NRIs (reboxetine in particular) have an effect on improving negative symptoms. However, we did not find evidence that NRIs have an effect on improving positive symptoms, cognitive functioning or incidence of nausea. One trial reported a benefit of reboxetine on quality of life scores. The results of our review should be viewed with caution as the quality of evidence available is very low due to the small size of studies and poor quality of the trials. In order to make firm conclusions regarding the effectiveness of NRIs for people with schizophrenia we need larger and better quality trials of NRIs. These should be long term and look particularly at negative and cognitive symptoms as well as side-effects.
However the review found that people have withdrawn from trials when they are assigned to a drug-free program. Consequently, there are no trials comparing methadone maintenance treatment with drug-free methods other than methadone placebo trials, or comparing methadone maintenance with methadone for detoxification only. These trials show that methadone can reduce the use of heroin in dependent people, and keep them in treatment programs.
We looked for randomised controlled trials comparing any of these topical treatments with placebo, no treatment or another topical treatment in adult patients undergoing nasal pharyngolaryngoscopy (NPL). We included eight studies in the review (with a total of 746 patients). It was not possible to combine data from any of the studies, therefore we assessed the individual study results. Five of the studies did not demonstrate any advantage, in terms of reducing pain or discomfort, of using a topical treatment prior to endoscopy. One of these suggested that a vasoconstrictor (xylometazoline) alone reduced the level of "general unpleasantness". Two studies did not compare the treatment against placebo or no treatment. A final study actually suggested an increase in pain with the use of topical agents. There may be some unpleasant side effects from the use of topical preparations, such as unpleasant taste. Further standardised research is required.
We identified 10 trials of moderate quality involving 654 participants and comparing SmartCare™ versus non-automated weaning strategies. Compared with non-automated strategies, SmartCare™ significantly decreased weaning time, time to successful removal from breathing machines and time spent in the ICU, with fewer patients receiving breathing machine support for longer than seven days and 21 days, and no increase in adverse events. SmartCare™ also showed a favourable trend toward fewer patients receiving ventilation for longer than 14 days, with no increase in adverse events. Subgroup analyses suggested more beneficial effects on weaning time in trials comparing SmartCare™ to a protocolized weaning strategy versus a non-protocolized control strategy. Sensitivity analyses, which excluded two trials with high risk of bias, supported significant reductions in weaning time with SmartCare™.
We searched medical databases for clinical studies where people were randomly put into one of two or more treatment groups including acupuncture treatment for women with PCOS who were infrequently or never ovulating. Acupuncture was compared with pretend acupuncture (sham), no treatment, lifestyle changes (e.g. relaxation) and conventional treatment. We included eight studies with 1546 women in this review. The studies compared true acupuncture versus sham acupuncture, clomiphene (medicines to induce ovulation), relaxation and Diane-35 (combined oral contraceptive pill); and low-frequency electroacupuncture (where small electrical currents are passed through the acupuncture needles) versus physical exercise. We included women who wanted to get pregnant and women who wanted regular ovulation and symptom control as our two main populations of interest. Our main interests were live birth rate, multiple pregnancy rate (for women who wanted to get pregnant) and ovulation rate (for women who wanted regular ovulation/symptom control). Due to the very low quality of the evidence and imprecise results, we were uncertain of the effect of acupuncture on live birth rate, multiple pregnancy rate and ovulation rate compared to sham acupuncture. For the same reasons, we were also uncertain of the effect of acupuncture on clinical pregnancy and miscarriage rate. Acupuncture may have improved restoration of regular menstrual periods. Acupuncture probably worsened side effects when compared to sham acupuncture. No studies reported data on live birth rate and multiple pregnancy rate for the other comparisons: physical exercise or no intervention, relaxation and clomiphene. Studies including Diane-35 did not measure fertility outcomes as women were only interested in symptom control. We were uncertain whether acupuncture improved ovulation rate compared to relaxation or Diane-35 (measured by ultrasound, which uses high-frequency sound waves to create an image, three months after treatment). The other comparisons did not report on ovulation rate. Side effects were recorded in the acupuncture group for the comparisons physical exercise or no intervention, clomiphene and Diane-35. These included dizziness, nausea (feeling sick) and bruising. The overall evidence was low or very low quality. There is currently insufficient evidence to support the use of acupuncture for treatment of ovulation disorders in women with PCOS. The evidence ranged from very low to moderate quality, the main limitations were not reporting important clinical results and not enough data.
We included 28 trials (2681 children under the age of 18 years and or their parents) with a large number of interventions (17) assessed. The presence of parents at induction of the child's anaesthesia has been the most commonly investigated intervention (eight trials), but has not been shown to reduce anxiety or distress in children, or increase their co-operation during induction of anaesthesia. Although parents should not be actively discouraged from being present if they prefer to do so, equally parents should not be encouraged to be present at their child's induction if they prefer not to do so. Most commonly other interventions are given to the child (e.g. video games or hypnosis) but sometimes the intervention is given to the parent. One study of acupuncture for parents found that the parent was less anxious, and the child was more co-operative, at induction of anaesthesia. Another study of giving parents information, in the form of pamphlets or videos, failed to show an effect. In other studies looking at interventions for children, clowns or clown doctors, a quiet environment, video games and computer packages (but not music therapy) each showed benefits such as improved co-operation in the children. Many of the studies were of poor quality and too small to provide clear answers to the study question. However potentially promising non-pharmacological interventions such as parental acupuncture; clowns/clown doctors; playing videos of the child's choice during induction, pre-operative hypnosis and hand-held video games require further testing in future studies. Non-drug interventions that might help parents relax need further study, as there is some evidence that more relaxed parents may improve their child's anaesthesia induction experience.
We evaluated the evidence from five randomised controlled trials that compared either different brands of alginate dressings, or alginate dressings with other types of dressings. In terms of wound healing, we found no good evidence to suggest that there is any difference between different brands of alginate dressings, nor between alginate dressings and hydrocolloid or plain non-adherent dressings. Adverse events were generally similar between treatment groups (but not assessed for alginate versus plain non-adherent dressings). Overall, the current evidence is of low quality. Further, good quality evidence is required before any definitive conclusions can be made regarding the use of alginate dressings in the management of venous leg ulcers.
We found two randomised trials, including 391 people with COPD. The participants had an average age of 68 years. The first study included three groups of COPD patients taking either moxifloxacin (daily for 5 days every 4 weeks), doxycycline (daily for 13 weeks) or azithromycin (3 times per week for 13 weeks). The second study investigated the use of doxycycline (daily) in addition to roxithromycin (daily) for 12 weeks in COPD. Our main outcomes were number of exacerbations, quality of life, serious side effects (known as 'adverse events') and antibiotic resistance. Overall, we were unable to determine any difference between one antibiotic compared with each other in improving the main outcomes we measured. We were unclear whether one antibiotic was better or worse than another in terms of reducing exacerbations or improving quality of life. Neither of the studies reported a comparison between antibiotics for drug resistance. In one study lasting 13 weeks we found no serious side effects of taking moxifloxacin, azithromycin or doxycycline, and no deaths were reported. In the other study, very similar numbers of people experienced serious side effects in both the combined antibiotic and single antibiotic treatment groups after 12 weeks of treatment and 48 weeks of follow-up. However, the numbers were small so we are not sure if one treatment option may cause more side effects than the other. In the same study, five people in the combined treatment group died, compared to three people in the single treatment group. Again, these numbers are too small to draw any conclusions. We were very uncertain about the results due to finding only two small studies that gave people with COPD antibiotics for only 12 or 13 weeks. The studies only looked at four different antibiotics and did not measure all the things we were interested in.
We searched for evidence on 1 November 2016 and identified 16 randomised controlled trials involving 4548 women for inclusion in the review. In studies where women received progesterone by injection into the muscle compared with placebo (dummy treatment) more women gave birth before the 34th week of pregnancy in the progesterone group (low-quality evidence). There was no clear difference between the groups in the likelihood of the baby dying before or soon after the birth (low-quality evidence). No studies reported whether any women died or whether any babies had longer-term developmental problems or disability. There seems to be little or no difference between women receiving progesterone or placebo for other important outcomes, such as preterm birth before 37 weeks (high-quality evidence); preterm birth before 28 weeks (moderate-quality evidence) or infant birthweight less than 2500 grams (moderate-quality evidence). No childhood outcomes were reported in the trials. In studies where women received vaginal progesterone there may be little or no difference between women receiving progesterone or placebo in preterm birth before 34 weeks (low-quality evidence); although fewer births before 34 weeks occurred in the progesterone group, this finding may have occurred by chance. The number of infant deaths before or soon after birth was similar in both groups (low-quality evidence). No studies reported maternal death or longer-term outcomes for babies. There may be little or no difference between groups receiving vaginal progesterone versus placebo in any other important outcomes (preterm birth before 37 weeks (moderate-quality evidence); preterm birth before 28 weeks (low-quality evidence); or infant birthweight less than 2500 grams (moderate-quality evidence)). No childhood outcomes were reported in the trials. For other outcomes, we found no clear group differences, except for caesarean section where women who received vaginal progesterone did not have as many caesarean sections as those in the placebo group (although the difference between groups was not large (8%)). Fewer infants whose mothers had received the vaginal progesterone needed mechanical help with breathing. We did not find any studies looking at progesterone taken by mouth. Overall, for women with a multiple pregnancy, treatment with progesterone (either intramuscular or vaginal) does not appear to reduce the likelihood of preterm birth or improve outcomes for babies. Future research could focus on looking at information about individual women taking part in studies, so that everything available about both intramuscular and vaginal progesterone treatments in women with a multiple pregnancy can be considered together.
In this review, both progestogen-only methods (pills and an intrauterine device) and low-dose combined oral contraceptives appeared to have only minor influences on glucose and fat metabolism. However only four studies, most of limited quality, examining a small number of women were included in this review. Only one of the studies reported on true clinical endpoints that is micro- and macrovascular disease. It found no signs or symptoms of thromboembolic incidents or visual disturbances. However this trial was performed over a short period of time. Therefore no definite conclusions can be made based on this review. Future trials analysing glucose and fat metabolism as well as long-term complications for all available contraceptive methods are needed.
We searched for evidence on 13 May 2016 and identified 24 studies involving 5577 women, and all these studies were of women at less than 13 weeks' gestation. There were a number of different ways of giving the drugs and so there are limited data for each comparison. Overall, the review found no real difference in the success between misoprostol and waiting for spontaneous miscarriage (expectant care), nor between misoprostol and surgery. The overall success rate of treatment (misoprostol and surgery) was over 80% and sometimes as high as 99%, and one study identified no difference in subsequent fertility between methods of medication, surgery or expectant management. Vaginal misoprostol was compared with oral misoprostol in one study which found no difference in success, but there was an increase in the incidence of diarrhoea with oral misoprostol.  However, women on the whole seemed happy with their care, whichever treatment they were given. The review suggests that misoprostol or waiting for spontaneous expulsion of fragments are important alternatives to surgery, but women should be offered an informed choice. Further studies are clearly needed to confirm these findings and should include long-term follow-up. There is an urgent need for studies on women who miscarry at more than 13 weeks' gestation.
This review includes 20 studies using a variety of measurements. One study included two measurements, for a total of 21 measurements assessed. The main feedback measurements we assessed were the level of carbon monoxide in people's breath (a sign of current smoking), measures of lung function (a sign of lung damage from smoking), genetic tests to provide individual risk of cancer, and ultrasound of major arteries in the neck to measure the amount of plaque (a risk factor for stroke). We grouped studies into three categories according to the type of feedback people were given: feedback on exposure to smoking (five studies); feedback on a person's risk for smoking-related diseases (five studies); and feedback on the harms of smoking (11 studies). The studies included a total of 9262 people. All participants were adult smokers, and both men and women were included (although one study performed in a clinic for army veterans included only 4% women). Most studies were conducted in general practices or ambulatory clinics. All of the studies lasted at least six months. The reported evidence is current as of March 2018. We did not find evidence that giving smokers feedback on their smoking exposure, their genetic risk of smoking-related disease, or the effects of smoking on their body helps them quit smoking. The most promising results were for giving people feedback on the harm smoking does to their bodies. The studies did not report on harms or side effects of providing feedback. However, given the nature of the measurements (lung or blood tests), we would expect the risk of harms to be low. Because of problems with the way some of the studies were conducted, we think that further research is likely to change our conclusions.
Since the best way to make such a determination is to undertake randomised trials, in which patients are assigned by chance to receive, or not receive, one or another of these treatments, this systematic review was undertaken to identify and summarise this information. Randomised trials comparing patients with liver diseases who were assigned to receive parenteral nutrition, enteral nutrition, or oral nutritional supplements to similar patients assigned not to receive any nutritional intervention were collected. The three nutritional interventions were considered separately. In addition, within each category of nutritional intervention, patients with medical conditions were compared separately from patients with surgical conditions. Thus there were six primary analyses, medical patients receiving or not receiving parenteral nutrition, surgical patients receiving or not receiving parenteral nutrition, medical patients receiving or not receiving enteral nutrition, surgical patients receiving or not receiving enteral nutrition, medical patients receiving or not receiving supplements by mouth, and surgical patients receiving or not receiving supplements by mouth. The outcomes of interest were mortality, hepatic morbidity (ascites, gastrointestinal bleeding, encephalopathy), quality of life, adverse events, infections, cost, duration of hospitalisation, jaundice, postoperative complications (only for the surgical trials), and nutritional outcomes (for example, body weight). A total of 37 randomised trials were identified. All but one had a high risk of systematic error (bias, that is overestimation of benefits and underestimation of harms). When the data were combined, most of the analyses failed to demonstrate a difference. There were some significant differences observed. These were that 1) parenteral nutrition reduced serum bilirubin more rapidly and improved one type of nutritional outcome (nitrogen balance) in medical patients with jaundice, and may have reduced some postoperative complications; 2) enteral nutrition may have improved nitrogen balance in medical patients, and reduced postoperative complications in surgical patients; and 3) supplements reduced the occurrence of ascites and also may have decreased the number of infections. Furthermore, the receipt of supplements (especially ones containing branched-chain amino acids) may have been helpful in the treatment of patients with hepatic encephalopathy. No significant effects were seen from the use of supplements in surgical patients. None of these observed benefits can be said to be definitively present because of the presence of methodologic flaws in the trials, which may have produced an overestimation of the observed effect. Moreover, due to too few patients included in the trials with two few outcome measures, both spurious significant findings and spurious insignificant findings cannot be excluded. The data are not strong enough to justify a recommendation to use these nutritional interventions routinely. We need well-designed and well-conducted randomised trials to prove that such therapy is indeed efficacious.
This review found that low heparin doses are effective in preventing catheters becoming blocked and needing to be re-inserted. There is not enough evidence to rule out the possibility of adverse effects. Heparin does not seem to lower the rate of blood clots in the major artery.
There is currently only one study reporting on 47 babies that fulfils our review criteria and compares different high dose versus low dose of initial replacement thyroxine for the treatment of congenital hypothyroidism. There is not enough evidence to suggest that a high dose is more beneficial than a low dose therapy. Growth and adverse effects were not reported in the included study. There should be more randomised controlled trials to assess the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.
Trials of sedatives have generally been of poor quality. Individual studies have reported that use of phenobarbitone compared to supportive care alone reduces the amount time an infant needs supportive care, is better than diazepam at preventing treatment failure and reduces the severity of withdrawal in infants treated with a opiate. In infants treated with an opiate, the addition of a sedative (phenobarbitone or clonidine) may reduce withdrawal severity, although safety and efficacy need confirming. The long term effects of use of phenobarbitone on an infant's development have not been determined.
The thorough literature search is up-to-date as of Febraury 2018. We found only one small randomised controlled trial (with 72 preterm infant participants) that addressed this question. We are uncertain as to whether re-feeding stomach aspirates has an effect on important outcomes such as incidence of necrotising enterocolitis, mortality before discharge, time to regain birth weight, time to reach full enteral feeds, duration of parenteral nutrition and duration of hospital stay. Available evidence is insufficient to support or refute re-feeding of stomach aspirates in preterm infants. More trials are needed to examine whether re-feeding the stomach aspirates is beneficial or harmful in preterm infants.
In January 2017 we searched for clinical trials in which gabapentin was used to treat neuropathic pain in adults. We found 37 studies that satisfied the inclusion criteria, randomising 5914 participants to treatment with gabapentin, placebo, or other drugs. Studies lasted 4 to 12 weeks. Most studies reported beneficial outcomes that people with neuropathic pain think are important. Results were mainly in pain after shingles and pain resulting from nerve damage in diabetes. In pain after shingles, 3 in 10 people had pain reduced by half or more with gabapentin and 2 in 10 with placebo. Pain was reduced by a third or more for 5 in 10 with gabapentin and 3 in 10 with placebo. In pain caused by diabetes, 4 in 10 people had pain reduced by half or more with gabapentin and 2 in 10 with placebo. Pain was reduced by a third or more for 5 in 10 with gabapentin and 4 in 10 with placebo. There was no reliable evidence for any other type of neuropathic pain. Side effects were more common with gabapentin (6 in 10) than with placebo (5 in 10). Dizziness, sleepiness, water retention, and problems with walking each occurred in about 1 in 10 people who took gabapentin. Serious side effects were uncommon, and not different between gabapentin and placebo. Slightly more people taking gabapentin stopped taking it because of side effects. Gabapentin is helpful for some people with chronic neuropathic pain. It is not possible to know beforehand who will benefit and who will not. Current knowledge suggests that a short trial is the best way of telling. The evidence was mostly of moderate quality. This means that the research provides a good indication of the likely effect. The likelihood that the effect will be substantially different is moderate.
The researchers identified two studies that included a total of 172 participants with moderate to severe ulcerative colitis who have failed treatment with immunosuppressives (e.g. steroids) or another biologic drug. Both studies compared etrolizumab to placebo (a fake medicine). Both studies were of high quality. The smaller study (48 participants) found no difference in remission rates between etrolizumab and placebo at week 10. The larger study (124 participants) found no difference between etrolizumab and placebo in the proportion of participants who achieved remission at week 6. However, there was a statistically meaningful difference in remission rates at week 10 favoring etrolizumab over placebo. In the larger study (124 participants) placebo participants were significantly more likely to have at least one side effect compared to those who took etrolizumab. Common side effects in this study included worsening ulcerative colitis, nasopharyngitis (common cold), nervous system disorders, headache and arthralgia (joint pain). In the other study (48 participants) there was no difference in the side effect rates between the placebo and etrolizumab groups. Common side effects in this study included worsening of ulcerative colitis, headache, fatigue (tiredness), abdominal pain, dizziness, nasopharyngitis (common cold), nausea, arthralgia (joint pain) and urinary tract infection. There was no meaningful difference between etrolizumab and placebo in the proportion of patients who experienced serious side effects. Serious side effects included worsening of ulcerative colitis and infection. Etrolizumab may be better than placebo for producing remission in people with moderate to severe ulcerative colitis who have failed other treatments. Different doses of etrolizumab were investigated but it is unclear what dose is most effective. More studies are required to determine the effectiveness and safety of etrolizumab in patients with moderate to severe ulcerative colitis. Currently there are seven ongoing studies investigating etrolizumab treatment for ulcerative colitis. These studies will provide important new information on the effectiveness, safety and ideal dose of etrolizumab for the treatment of people with moderate to severe ulcerative colitis.
This review includes 136 trials of NRT, with 64,640 people in the main analysis. All studies were conducted in people who wanted to quit smoking. Most studies were conducted in adults and had similar numbers of men and women. People enrolled in the studies typically smoked at least 15 cigarettes a day at the start of the studies. The evidence is current to July 2017. Trials lasted for at least six months. We found evidence that all forms of NRT made it more likely that a person's attempt to quit smoking would succeed. The chances of stopping smoking were increased by 50% to 60%. NRT works with or without additional counselling, and does not need to be prescribed by a doctor. Side effects from using NRT are related to the type of product, and include skin irritation from patches and irritation to the inside of the mouth from gum and tablets. There is no evidence that NRT increases the risk of heart attacks. The overall quality of the evidence is high, meaning that further research is very unlikely to change our conclusions.
We identified 13 randomised controlled trials (6923 participants), six for cardiac surgery (3359 participants) and seven for thoracic surgery (3564 participants). The evidence is current to May 2014. No study evaluated fondaparinux, the new oral direct thrombin or direct factor Xa inhibitors, or caval filters. Data could not be combined because of the different comparisons and the lack of data. Data for clinically relevant outcomes such as pulmonary embolism (blockage of one or more arteries of the lung) or major bleeding were often lacking. In cardiac surgery, symptomatic venous thromboembolism occurred in 71 out of 3040 participants from three studies. In a study of 2551 participants, representing 85% of the review population in cardiac surgery, the combination of unfractionated heparin with intermittent pneumatic compression was associated with an important reduction of symptomatic venous thromboembolism compared to unfractionated heparin alone. Major (important) bleeding was reported in one study only, and the best estimate was that bleedings occurred seven times more often in participants on vitamin K antagonists compared to participants on platelet inhibitors, but the true estimate may lay between one and a half to 30. In thoracic surgery, symptomatic venous thromboembolism occurred in 15 out of 2890 participants from six studies. Combined analysis could not be performed, but the largest study evaluating unfractionated heparin versus an inactive control did not show a benefit in terms of reduced occurrence of symptomatic venous thromboembolism. Major bleeding was reported in two studies that did not find significantly different rates between fixed-dose and weight-adjusted low molecular weight heparin (2.7% versus 8.1%) and between unfractionated heparin and low molecular weight heparin (6% and 4%). Overall, the evidence on the use of thromboprophylaxis in cardiac and thoracic surgery appeared to be scarce, so we are very uncertain about the benefit-to-risk balance. All studies had major study design flaws and most lacked a placebo or no treatment control group. We typically graded the quality of the overall body of evidence for the various outcomes and comparisons as low, due to imprecise estimates of effect and risk of bias. Our data suggest that thromboprophylaxis cannot be suggested for all patients undergoing these types of surgery, but should rather be considered case-by-case based on the individual risk of venous thromboembolism and bleeding.
Four databases were searched up to November 2013. We found 15 trials that met our inclusion criteria. Four trials included individuals with headache pain, 10 trials included individuals with non-headache pain, and one trial included individuals with both headache and non-headache pain. We looked at data about pain, disability, depression, and anxiety immediately after the end of treatment and between 3 to 12 months follow-up. We also looked at how satisfied people were with the treatments, and its effects on their quality of life. We found that for people with headache pain, pain symptoms and disability scores improved immediately following the end of treatment. However, only two trials could be entered into each of these analyses and so findings should be treated with caution. For people with non-headache pain, pain, disability, depression, and anxiety improved immediately after the end of treatment. Disability was also improved at follow-up. Only one study recorded quality of life scores in individuals with headache pain, so we were unable to analyse the results. Three studies presented quality of life scores for individuals with non-headache pain immediately following treatment. We did not find that quality of life improved after receiving the therapy. No data could be analysed on treatment satisfaction/acceptability. We conclude that these findings are promising for psychological treatments delivered via the Internet for the management of chronic pain in adults, but more trials are needed to determine the efficacy of such therapies.
Twenty-six trials presented sufficient data to be included in meta-analysis. There is some evidence from methodologically weak trials to indicate that some physiotherapy interventions are effective for some specific shoulder disorders. The results overall provide little evidence to guide treatment. There is a clear need for further high quality trials of physiotherapy interventions, including trials using combinations of modalities, in the treatment of shoulder disorders.
We identified 11 randomised controlled trials with a total of 1387 participants. Their average age was 69 years and all trials included men and women. The participants were randomised to have either balloon angioplasty alone or balloon angioplasty with stent placement. At two years, blood flowing through the narrowing in the arteries was no greater in participants with a stent inserted than in those without. There was a small improvement in the distance that the participants with a stent could walk up to one year later. However, when asked about their quality of life there was no improvement, whether a stent was placed or not, up to one year later. There were differences in the included trials; in some trials people with narrowings in other leg arteries were included. There were also differences between trials in the blood thinning drugs given after stent placement, which may change results, as these agents are important in keeping stents working in other parts of the body. These factors led us to the conclusion that there is a small benefit to adding a stent when performing balloon angioplasty for people in whom balloon angioplasty fails. However, there is insufficient evidence to support this approach as routine practice for everyone and future trials should examine whether subgroups of patients may benefit from stenting.
We searched the scientific literature for randomised controlled trials (experiments in which two or more interventions, possibly including a control intervention or no intervention, are compared by randomly allocating participants to study groups). We looked at the effectiveness of exercise-based rehabilitation compared with no exercise in adults (over 18 years of age) with heart failure. We considered HF due to reduced ejection fraction (HFrEF) (i.e. the chambers of the heart contract poorly, and, as a result, a smaller volume of blood is pumped around the body). We also considered HF due to preserved ejection fraction (HFpEF) (i.e. the chambers of the heart contract normally but do not relax efficiently, resulting in a smaller volume of blood pumped around the body). Our search is current to January 2018. We found 44 studies that included 5783 people with HF, mainly HFrEF. The findings of this update are broadly consistent with those of the previous (2014) version of this Cochrane Review. They show important benefits of exercise-based rehabilitation that include a probable reduction in the risk of overall hospital admissions in the short term, as well as the potential for reduction in heart failure admissions. The effect of exercise-based rehabilitation on health-related quality of life is uncertain due to very low-quality evidence. Exercise-based rehabilitation may make little or no difference in all-cause mortality in trials with follow-up less than 12 months. Further evidence is needed to better show the effects of exercise rehabilitation among people with HFpEF and the impact of alternative models of delivery, such as home-based programmes. Generally, recent trials have been better reported and are at low to moderate risk of bias. Using the GRADE method, we assessed the quality of evidence to range from high to very low across measured outcomes. Common reasons for downgrading outcomes include that results were inconsistent and/or imprecise.
We searched for randomized trials that compared waiting versus surgery for miscarriage. In addition, we looked at reference lists to find trials. We also wrote to researchers to find more studies. Seven trials with 1521 women looked at waiting versus surgery for miscarriage. More women who waited for the miscarriage to complete on its own had tissue left in the womb. This was studied at two weeks and at six to eight weeks. More of these women needed surgery to complete the process. These women also had more days of bleeding. Some needed to be given blood, compared with none in the surgery group. Both groups had about the same numbers of infections. Results were mixed for pain. Mental health also seemed about the same for both treatment groups. Costs were lower for waiting than for surgery. Overall, no strong medical results argue for either approach. Information was limited on future pregnancy. One trial was large, while the others had small numbers of women. What the woman prefers should be the major concern. Drug treatment (such as with misoprostol and mifepristone) has added choices for women and their clinicians, and has been studied in other reviews.
The included studies had an overall small number of participants and sessions. No included study compared breathing exercises alone versus a control. Instead, breathing exercises were part of a package of treatments and were compared to a control. The methods used to conduct the studies were not as well reported as we would like and so were unclear about the quality of the trials. Overall, we judged the included studies as being at an unclear risk of bias and the quality of the evidence included in the review was low. We could draw no reliable conclusions concerning the use of breathing exercises for children with asthma in clinical practice.
The evidence, where available, for each of seven main outcomes for all comparisons was of very low quality. This means that we are very unsure about the reliability of these results. The evidence for the comparison of exercise therapy versus control (e.g. no treatment) showed that exercise therapy may provide a clinically important reduction in pain during activity and usual pain in the short term (three months or less) and in the long term (more than three months). The review also found evidence that exercise therapy may provide a clinically important improvement in functional ability in both the short and long term, as well as resulting in greater numbers reporting recovery from their symptoms in the long term. The review found evidence that hip plus knee exercises may provide a clinically important reduction in pain during activity and usual pain in the short term and pain during activity in the long term, when compared with knee exercises only. There was inconclusive evidence to say whether functional ability or recovery was better in either group. This review has found very low quality but consistent evidence that exercise therapy for PFPS may result in clinically important reduction in pain and improvement in functional ability, as well as enhancing long-term recovery. However, we cannot say what is the best form of exercise therapy nor whether this result would apply to all people with patellofemoral pain. There is some very low quality evidence that hip plus knee exercises may be more effective in reducing pain than knee exercise alone. Before further studies are done, research is needed to identify priority questions and achieve better consensus on diagnostic criteria and measurement of outcome.
The review includes six trials with 1835 people. The trials randomised people with schizophrenia to receive either asenapine or placebo. Five of these trials had high rates of people leaving early and were sponsored by pharmaceutical companies. There is some evidence that asenapine, when compared to placebo, improves the positive, negative and depressive symptoms of schizophrenia while having less risk of debilitating side effects. However, due to the low quantity and limited quality of evidence currently available, it remains difficult to recommend the use of asenapine for schizophrenia. There is a need for large-scale, longer-term follow up, and bias-free randomised controlled trials investigating the effects and safety of asenapine. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/
Atypical antipsychotics have become the pharmacological treatment of choice for many clinicians in the treatment of behavioural and psychiatric symptoms in people with dementia, and the largest evidence base for double blind placebo controlled trials in this area is for risperidone. Particularly in view of recent safety concerns, a meta-analysis of efficacy and adverse events to inform clinical practice is timely. Modest efficacy is evident, but the elevated risk of cerebrovascular adverse events, mortality, upper respiratory infections, oedema and extrapyramidal symptoms is a concern, particularly as selective reporting makes interpretation of other potential adverse outcomes impossible.
The review included 12 randomised controlled trials (11 completed and one trial protocol (plan) - this trial was terminated early but reported some results on side effects) with 464 people with cystic fibrosis. Eight trials included only children, whilst four trials included both children and adults. The trials lasted between one and 12 months. Eight trials used a probiotic with a single type of bacteria and four trials used a probiotic with two or more types of bacteria. Only one trial compared different bacteria and the others compared probiotics to a placebo (dummy treatment with no active medication). Probiotics may reduce the rate of pulmonary exacerbations, however, this is not definite; pulmonary exacerbations are events where breathing symptoms are worsened (e.g. increased cough, sputum or shortness of breath) and lung function declines. Probiotics may reduce a marker of gut inflammation called calprotectin, however, the benefit of this to an individual is unknown. There were no differences between probiotics and placebo for height, weight or body mass index (BMI). Results did not show that probiotics affect lung function, need for admission to hospital or abdominal symptoms. One small trial measured quality of life and the parents questionnaire favoured probiotics, but the children's self report did not show a difference between probiotics and placebo. Probiotics may cause vomiting, diarrhoea and allergic reactions. We estimate 52 people need to take probiotics for one person to have an adverse event. We could not analyse the results of the trial comparing different probiotics because of its design. Future trials should look into the use of probiotics for at least 12 months and assess measures of lung and gut health, growth, abdominal symptoms, quality of life and adverse events. Given the wide range or probiotics (single and multi-strain combinations), doses used and degree of effectiveness, determining the best regimen(s) to investigate further will be challenging. There were several issues with the overall certainty of the evidence which affects our confidence in the results from these trials. We think the fact that some participants did not complete their treatment or were not included in the reports may affect the results on weight. We think the fact that not all planned outcomes were reported in four trials may affect the results of intestinal inflammation, growth and abdominal symptoms. We think the fact that the pharmaceutical industry sponsored at least four of the trials should be considered when looking at the results of this review. As most trials only included children we are not certain that the results would also apply to adults and there were also some issues related to whether people taking part in the trial knew which treatment they were receiving. We judged the certainty of evidence for changes in pulmonary exacerbations, intestinal inflammation, lung function, hospital admissions, weight and health-related quality of life to be low. Adverse events were only recorded by four trials and the protocol for the terminated trial and the certainty of the evidence was also judged to be low.
Our review was based on two identified randomised controlled study (involving 362 women) and found that prophylactic antibiotics may reduce the risk of intra-amniotic infection in women with MSAF (moderate quality evidence). Antibiotics use did not clearly reduce neonatal sepsis (low quality evidence), NICU admission (low quality evidence) or postpartum endometritis (low quality evidence). Studies with much larger numbers of pregnant women with MSAF would be needed to examine these issues.
We found one randomised controlled trial and nine observational studies that examined this question. Overall we found that in couples in which the infected partner was being treated with antiretroviral drugs the uninfected partners had, at worst, more than 40% lower risk of being infected than in couples where the infected partner was not receiving treatment. Since the World Health Organization (WHO) already recommends antiretroviral treatment for all persons with ≤350 CD4 cells/µL, we also examined studies that had studied couples in which the infected partners had CD4 counts higher than this level. We found that there is strong evidence from the randomised controlled trial that in this group HIV was less likely to be transmitted to uninfected partners from treated infected partners than from untreated infected partners.
This review investigates whether psychosocial interventions aimed at reducing antipsychotic medication in care homes are effective. By psychosocial interventions, we mean programmes that consist of different non-pharmacological components including talking to the staff, residents, or both. We identified four randomised controlled trials for inclusion in the review. All studies examined, among other components, education targeted at nursing staff in care homes. The methodological quality of three studies was limited, one study showed high quality. In all studies the interventions led to a reduction of antipsychotic medication use, but the overall magnitude of the effect remains unclear.
This review of 10 trials comparing either clopidogrel or ticlopidine with aspirin in about 27,000 people found that clopidogrel and ticlopidine were at least as effective as aspirin for the prevention of stroke and heart attacks, and might be slightly more effective. In terms of adverse effects, compared with aspirin, clopidogrel and ticlopidine caused less stomach upset and less bleeding from the gut, but more diarrhoea and skin rash. Ticlopidine produced more of these last two adverse effects than clopidogrel when compared with aspirin. Ticlopidine can also cause suppression of the bone marrow production of blood cells, which can be a serious complication. Clopidogrel is therefore the thienopyridine of choice since it is safer and better tolerated. However, since it is substantially more expensive than aspirin and not clearly more effective, it should generally only be used instead of aspirin in patients who are unable to take aspirin.
We first carried out a wide search of medical databases to find studies that met the requirements for this review. We identified three studies, which involved 277 participants who were randomly assigned to different treatments for pain in GBS. Two studies compared a pain medicine (gabapentin or carbamazepine) with placebo (inactive treatment). The other study compared a steroid medicine with placebo. Two medicines, gabapentin and carbamazepine, reduced pain severity compared to placebo (inactive) treatment and they had few side effects. One study found that people taking gabapentin had less pain, sleepiness or need for additional pain killers than those given carbamazepine. However, these studies were small and the treatment period was short. One trial, with 223 participants, found that methylprednisolone, which is a steroid medicine, did not affect the numbers of people who developed pain or change the numbers with more pain or less pain compared with placebo. This study did not report whether there were any side effects. This review does not provide enough evidence to say whether or not treatments for pain in people with GBS work. Although both gabapentin and carbamazepine reduced the severity of pain compared to placebo, and few side effects were reported, the studies were small and the quality of the evidence was very low. Much larger, well-designed studies are needed to confirm that drug treatments are safe and effective for people with pain in the period soon after onset of GBS. Long-term studies of pain treatments at the stage when people with GBS are recovering should also be conducted and these should include assessment of effects of pain treatments on quality of life. This review was first published in 2013 and an updated search in 2014 revealed no additional studies. The evidence is current to November 2014.
Authors included seven randomised controlled studies that involved 482 participants in our review. The studies were conducted in outpatient settings over four to 16 weeks; six were in USA and one in Australia. The mean age of participants was 34 years and 62% were males. No clear difference was found in the number of dropouts from an opioid agonist maintenance program between people receiving antidepressants and those in the placebo groups. Neither was drug use different (two studies). Severity of depression was reduced with the use of antidepressants (two studies), including tricyclic antidepressants. Adverse events were important as more of the participants who received antidepressants withdrew from the studies for medical reasons compared with those participants on placebo (four studies). The differences between studies in clinical (participant characteristics, the medications used, services and treatments delivered) and methodological characteristics (study design and quality) made it difficult to draw confident conclusions about the efficacy and safety of antidepressants for the treatment of depression in people who are dependent on opioids.
We searched for randomised controlled trials (experiments in which participants are randomly allocated to an experimental intervention compared with a control intervention) that investigated exercise-based interventions compared with no exercise intervention control. We found eight trials published from 2004 to 2017 with a total of 1730 participants. Two trials did not report on funding and one trial reported funding from industry. The evidence is current to 30 August 2018. The review showed no evidence of an impact on the risk of death, harmful side effects or having antitachycardia pacing or shock therapy when comparing the exercise intervention to the control. There was also little or no evidence of a difference on health-related quality of life. However, there was an improvement in exercise capacity in favour of the exercise group. The quality of the evidence ranged from moderate to very low for all outcomes. The number of events was low, it was possible for people in the trials to know to which intervention group they were randomised, the reporting of the results was not complete in some trials, and for some outcomes, the results varied across trials. These considerations limited our confidence in the overall results of the review. Further adequately powered and well-conducted randomised trials are needed to assess the impact of exercise-based cardiac rehabilitation in adults with an implantable cardioverter defibrillator.
We included 24 studies with a total of 581 participants. Lying on the front (the prone position) was better than lying on the back (the supine position) for oxygenating the blood but the difference was small. The increase in oxygen saturation on average increased by 2%. This finding was based on data from nine studies (195 children, 165 preterm and 95 ventilated) measuring this outcome. The rapid rate of breathing with respiratory distress was slightly lower in the prone position (on average four breaths/minute lower) based on six studies (100 infants aged up to one month, 59 ventilated). No adverse effects were identified. There were no obvious differences with other positions. As most of the 581 children in these studies were preterm babies (60%) and (70%) ventilated by machine, the benefits of prone positioning may be most relevant to these infants. ***It is important to remember that these children were hospitalised. Therefore, given the association of the prone position with sudden infant death syndrome (SIDS), the prone position should not be used for children unless they are in hospital and their breathing is constantly monitored. As the majority of studies did not describe how possible biases in the design of the study were addressed, the potential for bias in these findings is unclear. Also the findings of this review are limited by the small number of participants in studies, changes in infants and children were only measured for short time periods and the small changes in oxygenation which were seen in this review are not as meaningful as other measures of illness and recovery. Only five studies looked at children older than one year and few studies compared positions other than prone and supine.
In September 2019, we searched for clinical trials that used medicines in any setting to treat painful sickle cell crises. We found nine trials, with 594 adults (aged 17 to 42 years) who had sickle cell disease, experiencing a combined total of 638 painful episodes. The studies looked at different comparisons of the medicines butorphanol, cetiedil, fentanyl, ketoprofen, ketorolac, metoclopramide, morphine, paracetamol, placebo, tinzaparin, and tramadol. Only three studies compared the same two drugs (non-steroidal anti-inflammatory drugs such as ibuprofen, aspirin, or naproxen, with a placebo (pretend treatment)) and we had very limited data to be able to investigate the effects on pain scores from these medicines. Side effects were rare and were generally mild. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. For pain relief and side effects, we rated the quality of evidence as very low. We downgraded the quality of the evidence to very low because there were not enough data (e.g. too few participants). For some outcomes the quality of the evidence is unknown because there was no evidence available.
Our review included only randomised controlled trials (RCTs); we included 12 trials, containing a total of 615 people. In most cases, only a single trial that was too small to provide meaningful results investigated the treatments. There was no RCT evidence to support several quite commonly used treatments. The average duration of the trials was four months, long enough to check whether a treatment works initially but not long enough to show the duration of disease control or to detect delayed side effects. The evidence from two trials for clindamycin lotion applied to the skin and oral tetracyclines was relatively weak, despite these antibiotics being standard treatments for mild to moderate HS. There were four pharmaceutical industry-sponsored trials of anti-TNF-α (tumour necrosis factor-alpha) therapies, which included etanercept, infliximab, and adalimumab. Of these, a trial of etanercept did not find benefit, whereas a small trial of infliximab reported an improvement in quality of life after eight weeks. A larger trial, including 154 participants, investigated adalimumab. There was no benefit for moderate to severe HS at standard psoriasis doses of 40 mg every other week, but 40 mg weekly did improve quality of life. The estimate of quality of life improvement ranged from a level that probably would help people with HS to a level that might not be enough to justify use of adalimumab. The trial found no increase in serious side effects, including infections, but it was not large enough to detect rare effects. There were no trials investigating when to perform surgery or what surgical procedure to consider. One trial looked at inserting an antibiotic sponge into wounds after removal of HS lesions, but found no benefit compared with surgery without the antibiotic sponge. There were three trials of laser-type treatments, but the trial quality was too low to recommend these therapies. Our review has highlighted a need for more clinical trials to give better evidence to guide treatment choices in HS. More trials of oral treatments are required as well as surgical studies. Future trials should include patient-reported outcomes, such as quality of life and pain.
Two studies, including 374 women, compared preoperative radiotherapy and hysterectomy versus radiotherapy alone, but only one trial reported overall survival, with no difference between the groups. These studies found no difference in the risk of disease progression (or death) or five-year tumour-free survival. One study, including 61 women, reported no difference in overall and recurrence-free survival between chemotherapy and hysterectomy versus chemoradiotherapy alone. Another study comparing internal radiotherapy (brachytherapy) versus hysterectomy in 211 women who received chemoradiotherapy found no difference in the risk of death or disease progression. By combining results from three of the independent studies that assessed 571 women, we found that fewer women who received neoadjuvant chemotherapy plus hysterectomy died than those who received radiotherapy alone. However, many women in the first group also had radiotherapy. There was no difference in the number of women who were disease-free after treatment. Adverse events were incompletely reported. Results of single trials showed no differences in severe adverse events between the two groups in any comparison. Limited data suggested that the interventions appeared to be reasonably well tolerated, although more evidence is needed. Quality of life measures were not reported. We found insufficient evidence that hysterectomy added to radiation and chemoradiation improved survival, quality of life or adverse events in locally advanced cervical cancer compared with medical treatment alone. Overall, the quality of the evidence was variable and was universally downgraded due to concerns about risk of bias. The quality of the evidence for neoadjuvant chemotherapy and radical hysterectomy versus radiotherapy alone for survival outcomes was moderate, with evidence from other comparisons being of low quality. Further data from carefully planned trials assessing medical management with and without hysterectomy are likely to impact on how confident we are about these findings.
This review included 37 trials covering over 15,000 people who smoked tobacco. Studies were conducted in a lot of different types of people, including people with health problems or drug use problems, young people, homeless people, and people who had been arrested or were in prison. Some people felt ready to quit smoking and others did not. Motivational interviewing was provided in one to 12 sessions and took from as little as five minutes, to as much as eight hours, to deliver. Studies lasted for at least six months. The evidence is up to date to August 2018. There was not enough information available to decide whether motivational interviewing helped more people to stop smoking than no stop smoking treatment. People were slightly more likely to stop smoking if they were provided with motivational interviewing rather than another type of treatment to stop smoking, but our findings suggest that there is still a chance that motivational interviewing could also reduce a person's chances of quitting compared with other stop smoking treatments. This means more research is needed to decide whether motivational interviewing can help more people to quit than other types of treatment. Using longer motivational interviewing with more treatment sessions may help more people to give up smoking than shorter motivational interviewing with fewer sessions, however more research is needed to be sure that this is the case. We also looked at whether being provided with motivational interviewing to quit smoking increased people's well-being. Most studies did not provide any information about this, and so more studies are needed to answer this question. There is low-quality evidence looking at whether motivational interviewing helps more people to quit smoking than no treatment. This means it is difficult to know whether motivational interviewing helps people to quit smoking or not, and more studies are needed. The quality of the evidence was also low for all of the other questions we asked about quitting smoking, which means that our findings may change when new research is carried out. The quality of the research is rated as low because there were problems with the design of studies, findings of studies were very different to one another, and there were not enough data, making it difficult to determine whether motivational interviewing or more intense motivational interviewing helped people to quit smoking or not.
The haemopoietic colony stimulating factors (CSFs), granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF) are naturally occurring substances (cytokines) that can increase circulating white blood cells (neutrophils) and their ability to destroy bacteria. Common minor side effects are low grade fever and skeletal pain. The review authors identified seven treatment studies of 257 premature infants with suspected systemic bacterial infection. Adding G-CSF or GM-CSF to antibiotic therapy did not improve survival, overall. It may be, however, that infants who had clinically low neutrophils at the start of treatment did show some reduction in number of deaths by day 14 (taken from three studies). In three studies in which 359 low birthweight or premature neonates were treated preventatively (prophylaxis) no reduction in deaths was evident in those neonates receiving GM-CSF. GM-CSF was well tolerated with no adverse reactions in these small studies.
Only one new study met eligibility criteria for this review update, making at total of three included studies. TENS was given to 15 participants in one study, 41 participants in the other and 24 participants in the most recently included study. The newly included study suggested TENS might improve cancer bone pain on movement, but as a pilot study it was not designed to determine the impact of TENS on pain. The two studies in the previous review did not show that TENS significantly improved cancer pain. One study did not have sufficient participants to determine whether or not TENS had an effect. TENS was well tolerated in all three studies. There were significant differences in participants, treatments, procedures and symptom measurement tools used in the studies. In two of the studies some participants were able to identify when they received active TENS and when they received placebo. Consequently, there is insufficient evidence to judge whether TENS should be used in adults with cancer-related pain. Further research using well designed clinical trials is needed to improve knowledge in this field.
This review includes five studies with a total of 354 children and adults. All the trials compared once-a-day dosing with three times-a-day dosing. The review found that when treating people with cystic fibrosis for pulmonary exacerbations, giving the antibiotics once per day was just as good at as giving them more frequently in terms of lung function and body mass index. The review also found that giving the antibiotics once per day appeared to be less toxic to the kidneys in children. There were no differences between the different treatment schedules for other outcomes that the studies measured. While once-daily treatment can be just as effective and more convenient than three-times daily treatment, we recommend further studies to look at the long-term safety of this treatment schedule. We judged that just one of the five studies carried a low risk that any design factors might affect the outcome results. In the remaining four studies, we thought that the fact that it was obvious whether the antibiotics were given once or three times a day could affect some outcome measures (e.g. lung function). Other risk factors were unclear or at low risk of bias. We assessed the evidence for lung function, body mass index and the evidence for side effects (e.g. toxicity) to be moderate to low quality.
We identified 74 randomised clinical trials (5902 participants). Of these, 46 randomised clinical trials (4274 participants) provided information for one or more measures (outcomes). The trials included people with primary biliary cholangitis with and without symptoms; with and without antimitochondrial antibody (AMA) (an indicator of primary biliary cholangitis) regardless of whether they received previous treatments. The average follow-up period in the trials ranged from one month to eight years in the trials that reported this information. Funding: nine trials receive no additional funding or were funded by parties with no vested interest in the results. Thirty-one trials were partially or fully funded by the pharmaceutical companies that would benefit based on the results of the trial. The source of funding was not available from the remaining trials. The overall quality of evidence was very low and all the trials were at high risk of bias, which means that there is possibility of making wrong conclusions overestimating benefits or underestimating harms of one treatment or the other because of the way that the trials were conducted. There was no reliable evidence of decrease in the deaths between any of the interventions versus no intervention. There was no evidence of decrease in serious complications or complications of any severity between any of the treatments and no treatment. None of the trials reported health-related quality of life (a measure of a person's satisfaction with their life and health) at any time point. Overall, there is currently no evidence of benefit of any intervention in primary biliary cholangitis. There is significant uncertainty in this issue and further high-quality randomised clinical trials are required.
The searches are current to August 2014. We found three randomised controlled trials, which were done in the United States, the United Kingdom, and Australia. A total of 219 eyes were randomly allocated to treatment with CXL or no treatment. In all three studies the surgery was done in the same way. None of the studies included children. Eyes treated with CXL were less likely to have problems with progression of bulging compared to eyes that were not treated. However, the studies were small and there were some concerns about the way they were done. It is therefore difficult to say exactly how much the treatment helped. None of the studies reported the risk of eyesight getting worse but, on average, treated eyes had better vision (about 10 letters better) compared to untreated eyes. None of the studies reported on a change in quality of life for the participant. The main adverse effects were inflammation and swelling; this occurred in approximately one in 10 participants. We judged the quality of the evidence to be very low because of problems in the way the studies were done and reported and the small number of eyes included.
We included 18 studies (two randomized controlled trials and 16 prospective cohort studies) covering 11,043 women undergoing early medical abortion (up to nine weeks gestation) in 10 countries that compared self-administered medical abortion to provider-administered medical abortion, after an initial clinic visit. Most studies (16) were conducted in low-to-middle resource settings and two studies in high-resource settings. The evidence described in this review is from studies published before 10 July 2019. Women who self-administer medical abortion drugs in early pregnancy (up to nine weeks gestational age) experience similar rates of completed abortion as women who undergo provider-administered procedures in low-to-middle and high-resource settings. Evidence about safety is uncertain. The evidence for the success of self-administered medical abortion compared to provider-administered medical abortion was of moderate certainty, due to low-certainty studies. The evidence for the safety of these interventions was very low, due to low-certainty studies.
In this update search we found 39 new randomised controlled trials which, added to the 57 studies included previously, makes a total of 96 studies with 4512 participants. Twenty-one (21/39, 54%) of the new studies assessed new treatments, most of which involved the use of light. Narrowband UVB (NB-UVB) light was used in 35/96 (36% of all included studies), either alone or in combination with other therapies and achieved the best results. There were 18 surgical studies and 31 studies compared active treatment versus placebo. Half of the studies lasted longer than six months. Most of them 69/96 (72%) had fewer than 50 participants. Only seven studies assessed children and one study only recruited men. The majority of studies (53/96, 55%), most of which were of combination treatments with light, assessed more than 75% repigmentation. Eight studies reported a statistically significant result for this outcome, including the following four results: topical corticosteroids were better than PUVAsol (psoralen with sunlight), hydrocortisone plus laser light was better than laser light alone, ginkgo biloba was better than placebo and oral minipulse of prednisolone (OMP) plus NB-UVB was better than OMP alone. None of the studies reported the long-term benefit of the treatment i.e. two years' sustained repigmentation. The maximum follow-up time, reported in only one study, was one year post-treatment. Only 9/96 (9%) reported the quality of life of participants, but the majority of all studies (65/96, 68%) reported adverse effects, mainly for topical treatments, some of which caused itching, redness, skin thinning, telangiectasia and atrophy. Neither mometasone furoate nor hydrocortisone produced adverse effects. Some NB-UVB studies reported phototoxic reaction and Koebnerisation whereas some PUVA (psoralen with artificial light UVA as a light source) studies caused dizziness and nausea. Six studies reported cessation of spread of vitiligo, one of which showed that ginkgo biloba was more than twice as likely to stop vitiligo spreading than placebo. This review has highlighted the recent surge in vitiligo research providing insights into its causes. The majority of the studies reporting successful repigmentation were combinations of various interventions with light, indicating this is an effective, though not necessarily permanent, treatment for generalised vitiligo. In view of the fact that vitiligo has no cure, providing ways of coping with it could be of benefit to patients and should be part of standard care. Better designed studies, consensus on how to measure treatment success, more studies involving children and studies assessing psychological interventions, are needed. Since the last update (2010), the design and reporting of vitiligo trials have not greatly improved. Only five studies met the criteria for a well-designed trial. Poor design, the number and complexity of the treatments and the fact that many of the studies assessed individual vitiligo patches in the same participant, made comparison of the studies difficult. Consequently, we could only perform one meta-analysis of three studies comparing NB-UVB with PUVA which showed that NB-UVB has fewer side effects and is marginally better than PUVA.
Nine studies including 808 premenopausal women with uterine fibroids compared various methods of myomectomy. These studies were conducted in Italy (seven studies), Austria and China. The evidence is current to July 2014. Myomectomy by laparoscopy is a less painful procedure compared with open surgery. Postoperative pain was measured on a visual analogue scale (VAS), with zero meaning 'no pain at all' and 10 signifying 'pain as bad as it could be.' Results show that among women undergoing laparoscopic myomectomy, the mean pain score at six hours (mean difference (MD) -2.40, 95% confidence interval (CI) -2.88 to -1.92) and at 48 hours (MD -1.90, 95% CI -2.80 to -1.00) would be likely to range from about three points lower to one point lower on a VAS zero-to-10 scale. Results of our analysis regarding pain score at 24 hours were uncertain (MD -0.29, 95% CI -0.70 to 0.12). Risk of fever after the operation was reduced by 50% in women undergoing laparoscopic myomectomy (OR 0.44, 95% CI 0.26 to 0.77). Drop in haemoglobin level (indicating reduced blood loss) could not be compared because results of the analysis were not conclusive because of differences in results with even the same surgical techniques. Risk of injury to intestines and other organs could not be determined in this meta-analysis. No evidence was found of increased risk of recurrence of fibroids after laparoscopic surgery compared with open surgery (OR 1.12, 95% CI 0.63 to 1.99). The quality of the evidence ranged from very low to moderate. Some outcomes involved small numbers of participants, poor information about blinding in included studies and very wide confidence intervals.
In September 2016, we searched the medical literature and found five studies involving 1812 participants looking at aspirin for frequent episodic tension-type headache. About 1668 participants were involved in comparisons between aspirin at doses between 500 mg and 1000 mg and placebo (a dummy tablet). The International Headache Society recommends the outcome of being pain free two hours after taking a medicine, but other outcomes are also suggested. No studies reported pain free at two hours, or other recognised outcomes, so there was limited information to analyse for outcomes about how well aspirin works. None of the studies reported on participants being pain free at two hours, and only one study reported an outcome we judged equivalent to being pain free or having only mild pain at two hours. For aspirin 1000 mg, about 10 participants in 100 used additional painkillers, compared with 30 in 100 with placebo (very low quality evidence). At the end of the study 55 in 100 participants were 'satisfied' with treatment compared with 37 in 100 with placebo (very low quality evidence). About 15 in 100 people taking aspirin 1000 mg reported having a side effect after one dose, which was the same as with placebo (low quality evidence). The quality of the evidence was low or very low for the comparisons between aspirin and placebo. Low and very low quality evidence means that we are very uncertain about the results.
We identified five studies (involving a total of 805 women) that evaluated effectiveness of analgesia for pain during amniocentesis. Types of analgesia included local anaesthetics (either injected (two studies, 423 women) or applied topically (one study, 120 women)); use of a subfreezing (-14°C) needle (one study, 62 women); and leg rubbing (one study, 200 women). We found no studies evaluating analgesia during chorionic villus sampling. Each comparison failed to demonstrate positive affect on pain during amniocentesis. In general, women who undergo amniocentesis could be informed that pain during procedure is minor and that there is currently insufficient evidence to support the use of local anaesthetics, leg rubbing or subfreezing the needle for pain reduction during this procedure.
This review of the research on the effect of an antidepressant drug called paroxetine was conducted to shed light on the field of drug treatment for depression. In September 2012 we searched, in a wide ranging way, for all the useful studies (randomised controlled trials) which had been completed which compared paroxetine with any other antidepressant in treating people with depression. One hundred and fifteen studies were included in this review, with a total of 26,134 people. We grouped the studies according to the types of drug they compared paroxetine against; we then analysed the combined findings of these groups of studies. For the primary outcome (number of people who responded to treatment) paroxetine was more effective than reboxetine, but less effective than mirtazapine (in the early phase: one to four weeks follow-up) and probably citalopram (at endpoint: six weeks follow-up). There was some evidence that paroxetine is less well tolerated than agomelatine and St John's Wort, as more patients allocated to paroxetine experienced at least some side effects (though this finding for St John's Wort was only based on one study). In conclusion, some possibly meaningful differences between paroxetine and other antidepressants exist, but no definitive concluions can be drawn due to the limited number of studies per comparison. In addition, most of included studies were sponsored by the drug industry, which means they might potentially have overestimated the effect of paroxetine. Therefore, the results of this review should be interpreted with caution.
Currently, no evidence from randomised controlled trials suggests that beta blockers adversely affect walking distance in people with intermittent claudication, and beta blockers should be used with caution, if clinically indicated. The review authors identified six randomised controlled trials that involved a total of only 119 people with mild to moderate peripheral arterial disease. The beta blockers studied were propranolol, pindolol, atenolol and metoprolol. None of the trials showed clear worsening effects of beta blockers on time to claudication, claudication distance and maximal walking distance as measured on a treadmill, nor on calf blood flow, calf vascular resistance and skin temperature, when compared with placebo. Trial investigators reported no adverse events or issues regarding taking the beta blockers studied. Most of the trials were over 20 years old and reported findings between 1980 and 1991. All were small and of poor quality. The drugs were administered over a short time (10 days to two months), and most of the outcome measures were reported in single studies. Additional drugs－calcium channel blockers and combined alpha and beta blockers－were given during some of the trials.
Overall 223 patients with differentiated thyroid cancer participated in four studies. The duration of the intervention (injections of recombinant human thyrotropin) was two days in all trials. Studies were of rather low quality. We found no statistically significant differences between recombinant human thyrotropin and thyroid hormone withdrawal treatment in terms of successful reduction of thyroid remnants or cancer cells but significant benefits in radiation exposure to blood and bone marrow. One trial reported on benefits in some domains of health-related quality of life. There were no deaths and no serious adverse effects observed, however maximum follow up was only 12 months. None of the included trials investigated complete or partial remission of metastatic tumour, secondary malignancies or economic outcomes. We did not find sufficient data comparing recombinant human thyrotropin with thyroid hormone withdrawal-aided radioiodine treatment for metastatic differentiated cancer.
fifteen studies were included on 425 participants with COPD. However, only 12 studies provided sufficient information for analysis across one or more of the three comparisons described above. when arm training was compared to no arm training or a sham intervention in people with COPD, there was a small improvement in breathlessness. However, this improvement was not evident when the studies of combined arm and leg training were compared to leg training alone. No studies have examined whether breathlessness improves more with different types of arm training. Arm training had no effect on quality of life in any of the three comparisons. When endurance arm training was specifically examined, there was an improvement seen in the capacity of the arms to move and lift light weights compared to no training. These effects were not seen with arm strength training. the quality of the included studies was low to moderate due to the small number of participants (ranging from 12 to 43 participants per study), missing information on the methods of the study, and incomplete data on the outcomes. some form of arm training can provide a small improvement to breathlessness but does not improve the quality of life of people with COPD. More specifically, endurance arm training can increase the capacity of the arms to move light weights in people with COPD.
The evidence is current to March 2014. In total, we included 31 studies (with 3231 participants) in our review. Of those 31 studies, 28 (2976 participants) provided data for the meta-analyses. The mean age of the participants varied from 75 to 86 years. Those studies were published between 1977 and 2013 and so covering a wide range of clinical practices and improvements in techniques over time. Two studies were funded by the anaesthetic drug manufacturer or by an agency with a commercial interest, one received charitable funding, and one was funded by a government agency. We reran the search in February 2017. Potential new studies of interest were added to a list of "Studies awaiting Classification" and will be incorporated into the formal review findings during the review update. The trial reports of many of the studies indicated a sub-suboptimal level of methodological rigour and the number of participants included was often insufficient to allow us to draw a definitive conclusion on many of the outcomes studied. We did not find any difference in mortality at one month (11 trials with 2152 participants) between neuraxial blocks and general anaesthesia. We also did not find a difference for pneumonia, myocardial infarction, cerebrovascular accident, acute confusional state, congestive heart failure, acute kidney injury, pulmonary embolism, number of patients transfused with red blood cells, length of surgery and length of hospital stay between these two anaesthetic techniques in two to twelve studies. Likewise, when potent prophylactic drugs (such as low molecular weight heparin) were used against postoperative clot formation, we did not find a difference in the risk of deep venous thrombosis. Without prophylaxis with potent anticoagulant drugs the risk of deep venous thrombosis was less with neuraxial block. The level of evidence was very low for mortality, pneumonia, myocardial infarction, cerebrovascular accident, acute confusional state, decrease in the incidence of deep venous thrombosis in the absence of potent prophylaxis, and return of patient to their own home. This means that any estimate of effect is very uncertain.
This review shows that little research has been done to find the best ways of involving consumers in healthcare decisions at the population level. Most of the included trials compared consultations with consumers with no consultations with consumers. There is moderate quality evidence from two trials that involving consumers in the development of patient information material results in material that is more relevant, readable and understandable, without affecting anxiety. This 'consumer-informed' material can also improve knowledge. Two trials, which compared using consumer interviewers with staff interviewers as data collectors for patient satisfaction surveys, found small differences in satisfaction survey results, with less favourable results obtained when consumers were the interviewers. One trial comparing two informed consent documents, one developed with consumer input and the other developed by the trial investigators, showed that consumer input may have little if any impact on understanding of the trial described in the consent document. One trial, comparing two different methods for involving the public (telephone discussion and a face-to-face group meeting), showed that a face-to-face meeting is most likely to engage consumers and may result in different community health priorities.
We searched the medical literature for randomized controlled trials (a type of study in which participants are assigned to a treatment group using a random method) in March 2018. Participants were randomly allocated to one of two groups. One group was treated with opioids before the surgeon cut the skin, whilst the other group was given the same medication after the surgeon cut the skin. We identified 20 trials involving a total of 1343 participants aged over 15 years who were undergoing a variety of surgeries. In all but one trial, participants received general anaesthetic. Nearly all participants were low-risk patients. Only one of the trials used a pre-emptive dose of opioid. Key results In one small trial (40 participants) involving people undergoing dental surgery, use of pre-emptive opioids resulted in a small reduction in pain experienced in the first six hours after surgery and at 24 to 48 hours based on low-quality evidence. This study did not report on adverse events or 24-hour morphine consumption. For preventive opioids started before the first cut was made and continued over the first day after surgery, pain in the first six hours after surgery was similar to when the first opioid dose was given after the first cut to the skin (10 studies; 706 participants). Postoperative pain 24 to 48 hours after surgery was similar between groups (9 studies; 668 participants). The evidence for both these findings was of moderate quality. The following findings were supported by low- or very low-quality evidence. A reduction in 24-hour morphine consumption was too small to be clinically relevant (11 studies; 526 participants). Not all studies reported on adverse events, but the numbers of participants with respiratory depression (4 studies; 433 participants), low heart rate (2 studies; 112 participants), or low blood pressure (2 studies; 88 participants) were similar between groups. Quality of the evidence The quality of the evidence ranged from very low to moderate. The main issues concerning the included trials were high risk of bias due to limitations in how the findings were presented, the design and conduct of the studies, and wide variations in the findings, which led to uncertainty in the results. Consequently, we found no convincing evidence that starting opioids before the beginning of surgery reduces levels of pain after surgery or the need for continuing opioids.
In April 2018, we searched for randomised controlled trials (RCTs) that had compared reduced-dose radiotherapy/chemotherapy treatment with standard-dose treatment. We were interested in the outcomes of overall survival and disease-free survival, as well as the effects on swallowing ability and voice. Our searches did not identify any completed RCTs, however three relevant studies are ongoing and the first results are expected between 2021 and 2023. Currently there is no high-quality evidence comparing these two treatments, however such trials are in progress.
The main aim of this review was to determine the best range of doses of haloperidol for the treatment of schizophrenia. Nineteen trials were included that compared varying doses of haloperidol. Despite over 30 years of trials, data on the effects of differing doses of haloperidol are sparse and poorly reported. This is especially so for the lower dose ranges generally used for the treatment of schizophrenia today. However, lower doses of haloperidol may be just as effective as higher doses but result in fewer side effects. This review also suggests that an important bias against haloperidol may exist in modern trials comparing new drugs with haloperidol. Results are not conclusive and are based on small, short studies of limited quality. The authors of the review note that it would be understandable if psychiatrists were cautious about prescribing doses above 7.5 mg a day and if people with schizophrenia did not want to take higher dosages. Further research is needed to assess the tolerability and effectiveness of lower doses. Low doses of haloperidol may be just as good as higher doses, but with fewer side effects. This plain language summary was written by a consumer, Benjamin Gray, Service User and Service User Expert. Rethink Mental Illness. Email: [email protected].
No trials were found comparing these different methods with each other. Sometimes people using the catheters develop urinary tract infections. There was some weak evidence that using antibiotics all the time reduced the chance of having a urinary tract infection while using intermittent catheters, but there was not enough information about side effects.
We found one controlled clinical trial (poor quality) that compared multidisciplinary rehabilitation to standard outpatient care. The 106 people in this trial received treatment in the hospital outpatient clinic. Participants were in the multidisciplinary rehabilitation programme for up to eight weeks, and the results were measured at three and six months after completion of the programme. There was some evidence to support the benefit of multidisciplinary rehabilitation in reducing disability in people with primary brain tumour. People in the multidisciplinary rehabilitation group showed improvement in their functional abilities (e.g. continence, mobility) and cognitive function compared to the group with standard care only. Multidisciplinary rehabilitation was not harmful. Current research gaps highlight the need for high-quality research to explore the effectiveness of various aspects of multidisciplinary rehabilitation and caregiver needs in this patient population. The evidence in this review is up to date to January 2015.
This is an update of the original review in 2010. We considered studies comparing circuit class therapy with conventional therapy for people with stroke, and included only high-quality studies with a low risk of being biased. We were interested in studies that compared these two approaches and their effects on the way people walk, how far, how fast, and how independently. We also looked for studies that investigated if the circuit classes were more or less likely to be harmful than conventional approaches. The evidence is current to January 2017. We found seventeen studies, involving 1297 participants, that compared circuit class rehabilitation with usual care or sham rehabilitation. Most trials reported the benefits of circuit classes for improving walking ability. More specifically, we combined the results from the studies and found moderate evidence that circuit classes were more effective in improving the person's ability to walk further, more independently, and faster and, in some cases, to balance more easily and confidently when compared with other types of therapy. There was a suggestion that people might fall more often in the circuit classes, and that they may be able to get home from rehabilitation hospital more quickly, but these two aspects were not confirmed using statistics. We also found that the positive effects of the circuit classes were experienced equally by people who had had their stroke more than a year ago compared with people who had had their stroke within the year. This means people can continue to improve longer after their stroke than was previously reported. More research is needed to see if it works for all people with any severity of stroke and if some tasks are better to practise than others. The quality of the studies overall was acceptable, given it is difficult to keep some aspects tightly controlled in rehabilitation studies. However, we have downgraded the quality rating to 'moderate' to acknowledge that some trials have the potential for bias.
The evidence is current to April 2016. We found two cohort studies (where a group of people (the cohort) is followed over time, to examine different treatments received and subsequent outcomes) looking at 131I-MIBG treatment in 60 children with newly diagnosed HR NBL. The studies were not comparable with regard to the children, the ways they were treated and the ways the different outcomes were defined and so it was impossible to combine the results in an analysis. Not all relevant outcome results were available. The percentages of children whose cancer reduced or disappeared after treatment (response rate) were 56% and 73% in the two studies, but survival was still poor: overall survival (length of time that the child remained alive) was about 15 months, event-free survival (time during which there were no objective signs of tumor recurrence) was about 10 months. Overall survival five years after treatment was 14.6%, and after 10 years was 12.2%. With regard to short-term side effects, there were some low blood cell counts. There was no liver toxicity. The studies did not report on heart problems and infections of the salivary glands. One study assessed long-term side effects in some of the children: there was some evidence of thyroid (a gland in the neck) problems, which was brief in three children, but remained high in seven children, of whom five were prescribed medicine. There were no secondary cancers (where a different type of cancer has returned following the original cancer). Based on the currently available evidence, we cannot make recommendations for the use of 131I-MIBG therapy in patients with newly diagnosed HR NBL in clinical practice. More high-quality research is needed before definite conclusions can be made. All studies had problems relating to quality of the evidence.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed medications worldwide and are commonly used for treating low-back pain. This review found 65 studies (including over 11,000 patients) of mixed methodological quality that compared various NSAIDs with placebo (an inactive substance that has no treatment value), other drugs, other therapies and with other NSAIDs. The review authors conclude that NSAIDs are slightly effective for short-term symptomatic relief in patients with acute and chronic low-back pain without sciatica (pain and tingling radiating down the leg). In patients with acute sciatica, no difference in effect between NSAIDs and placebo was found. The review authors also found that NSAIDs are not more effective than other drugs (paracetamol/acetaminophen, narcotic analgesics, and muscle relaxants). Placebo and paracetamol/acetaminophen had fewer side effects than NSAIDs, though the latter has fewer side effects than muscle relaxants and narcotic analgesics. The new COX-2 NSAIDs do not seem to be more effective than traditional NSAIDs, but are associated with fewer side effects, particularly stomach ulcers. However, other literature has shown that some COX-2 NSAIDs are associated with increased cardiovascular risk. The review noted a number of limitations in the studies. Only 42% of the studies were considered to be of high quality. Many of the studies had small numbers of patients, which limits the ability to detect differences between the NSAID and the control group. There are few data on long term results and long-term side effects.
This review included 29 randomised controlled trials with 4290 patients. The trials showed modest reductions in total blood loss or red cells transfused (equivalent to less than one unit of red cell transfusion) with the use of rFVIIa. However, the reductions were likely to be overestimated due to the limitations of the data. We also observed an increase in the risk of having a blood clot in the arteries (such as a heart attack or stroke) in those patients receiving rFVIIa. When taken together, the data supporting the off-license use of recombinant FVIIa are weak. The use of rFVIIa outside its current licensed indications should be restricted to clinical trials.
We identified five studies to 30 July 2019 including a total of 5039 participants. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. Four studies included participants who had no history of diabetes, and one study included only participants with diabetes. Compared with placebo tablets, PPAR-γ agonists reduced recurrent strokes and other blood vessel disease, improved the body's response to insulin, and stabilised fatty deposits in artery walls. The drugs also appeared to be well tolerated, but the evidence for this was inconclusive. Our conclusions should be interpreted with caution considering the small number of included studies and the limited quality of some of the studies. Further well-designed randomised controlled trials with large sample sizes are required.
Five randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 639 women were included in the review. Three compared UTND to LOD, and two compared UTND combined with gonadotropins to gonadotropins. UTND versus LOD The quality of the three studies was low to very low. None of the studies reported on the main outcome of live birth. Based on currently available evidence, we are uncertain whether pregnancy rate of women using UTND is different from that of LOD. UTND may lead to a small decrease in ovulation rate when compared to LOD. Thus, low-quality evidence suggests that among clomiphene-resistant women with PCOS using LOD with an expected ovulation rate of 69.5%, the rate among women using UTND may be between 50.6% and 68.8%. There is insufficient evidence to reach conclusions regarding surgical complications and miscarriage, as we found only one very low-quality study. None of the studies reported OHSS or multiple pregnancy rate. UTND combined with gonadotropins versus gonadotropins alone We were unable to assess the benefit or harm of applying UTND combined with gonadotropins for women with clomiphene-resistant PCOS, as we identified only two very low-quality trials that used different doses of gonadotropins. We assessed the quality of the evidence as low to very low due to poor explanations of study methodology and the limited number of included trials. Also, reporting on clinically relevant issues that are important for subfertile couples, such as live birth, was lacking.
We searched for trials on 11 May 2017. We included 70 studies though only 61 studies involving more than 8000 women contributed data to the review. All of the trials were conducted in hospital settings, on healthy women with uncomplicated pregnancies at 37 to 42 weeks' gestation. The trials compared an opioid (intramuscular or intravenous) with placebo (dummy treatment), no treatment, another opioid (or in three trials another medication or inhaled nitrous oxide) or transcutaneous electrical nerve stimulation (TENS) in 34 different comparisons. There were few opportunities to pool the findings, and for many outcomes only one trial contributed findings. The quality of the evidence was mainly assessed as low or very low for the outcomes of pain in labour and satisfaction with analgesia. Many of the studies included insufficient numbers of women to detect differences between groups. Overall, our findings indicate that opioids provided some pain relief during labour, although substantial proportions of women still reported moderate or severe pain. Opioid drugs were associated with nausea, vomiting and drowsiness, with different types of opioids causing different side effects. We did not have sufficient evidence to assess which opioid drug provided the best pain relief with the least adverse effects. Nor did we find clear evidence of adverse effects of opioids on the newborn. Maternal satisfaction with opioid analgesia appeared moderate although it was often unreported or reported in different ways. We did not have sufficient evidence to assess which opioid drugs women were most satisfied with. In this review we did not examine the effectiveness and safety of intramuscular or intravenous opioids compared with other methods of pain relief in labour such as epidural analgesia. The review needs to be examined alongside related Cochrane reviews. As injected opioid drugs are so widely used it is important that more research is carried out so that women can make informed choices about pain relief.
Sixteen trials with 1233 participants were included, most of whom had severe COPD. The breathing techniques studied included pursed lip breathing (breathing out slowly with the lips in a whistling position), diaphragmatic breathing (deep breathing focusing on the abdomen), pranayam yoga breathing (timed breathing with a focus on exhalation), changing the breathing pattern using computerised feedback to slow the respiratory rate and increase exhalation time, or combinations of these techniques. The study quality was generally low. Breathing exercises appeared to be safe for people with COPD. Yoga breathing, pursed lip breathing and diaphragmatic breathing improved the distance walked in six minutes by an average of 35 to 50 metres in four studies. Effects of breathing exercises on shortness of breath and well being were variable. When added to whole body exercise training, breathing exercises did not appear to have any additional benefit.
We searched for randomised controlled trials comparing different phototherapies, or comparing phototherapy with other treatments or a placebo (sham treatment), for foot ulcers in adults with diabetes in October 2016. We included eight trials (316 participants). Most studies were undertaken in clinics or hospitals and had small numbers of participants (14 to 84). The average age in the included studies was from 53 to 68 years, and the ratio of females to males was 0.46 to 1.88. The included studies compared phototherapy with placebo or no phototherapy, on top of usual care (usual care could include treatments such as dressings, antibiotics, or wound cleaning). Treatment times ranged from 15 days to 20 weeks. The results suggested that phototherapy, when compared to no phototherapy or a placebo, may increase the proportion of wounds completely healed during follow-up and reduce wound size. However, as the included studies involved small numbers of participants and had drawbacks in study methods, our confidence in these results is limited. We did not find sufficient evidence that the potential harms or incidence of amputations differed between the phototherapy group and the no phototherapy/placebo group. We judged the quality of the evidence to be low due to a lack of data and risk of the study results being biased. Further high-quality studies are needed to confirm the benefits and harms of phototherapy. This plain language summary is up to date as of 26 October 2016.
We searched databases for studies up to the October 2018, and found 15 studies with 7976 children. Eight studies were conducted in Malawi, four in India, and one apiece in Kenya, Zambia, and Cambodia. One small study included only children infected with HIV, another study analysed children with and without HIV separately for the main outcome (recovery), while the other studies included children who were not infected with HIV or who were untested. Overall, we judged six studies to be at high risk of bias, three studies to be at unclear risk of bias, and six studies to be at low risk of bias. (With 'risk of bias', we mean the extent to which the methods used in a study enable it to determine the truth.) All the studies lasted between 8 and 16 weeks. Only five studies followed up children after the study (for a maximum of six months), and generally reported on a limited number of outcomes. Of our 15 included studies, six were linked to funding or donations from industry, one did not report the source of funding, and eight studies reported funding where sponsors did not include industry. Compared to alternative dietary approaches, standard RUTF probably improves recovery (moderate-quality evidence) and may increase the rate of weight gain slightly (low-quality evidence), but the effects on relapse and death are unknown (very low-quality evidence). With 'quality of evidence' we mean how confident we are that the particular finding represents the true effect. For example, 'very low-quality' means we are very uncertain about the finding, 'low-quality evidence' means the future research is very likely to change the finding, 'moderate-quality evidence' means that future studies may change this finding, and 'high-quality evidence' means that it is unlikely that future studies will change the finding. Standard RUTF meeting total daily nutritional requirements may improve recovery and relapse compared to a similar RUTF given supplementary to the usual diet (low-quality evidence), but for death and the rate of weight gain, the effects are not known (very low-quality evidence). When comparing RUTFs of different formulations, it makes little or no difference for recovery whether a standard or alternative formulation RUTF is used (high-quality evidence). For relapse, using standard RUTF decreases relapse (high-quality evidence). It probably makes little or no difference to death (moderate-quality evidence) and to the rate of weight gain (low-quality evidence) whether standard or alternative formulation RUTF is used. Well-designed, randomised controlled trials (experimental studies where participants meeting the inclusion criteria have an equal chance of being allocated to any of the intervention or control groups) in which analyses have been performed separately for children with and without HIV, and that also measure and report on diarrhoea occurrence, are needed.
This review aimed to compare the effects of in utero repair versus repair as a newborn. We included one randomised controlled trial involving 158 women who were from 19 to 27 weeks pregnant with a baby with severe spina bifida and evidence of hindbrain herniation. For neonatal mortality, there was no clear difference identified for prenatal versus postnatal repair. However, the numbers of neonates who died were low and so the review was likely underpowered to detect any difference. Prenatal repair was associated with reduced need for shunt placement and a reduction in the risk of moderate to severe hindbrain herniation after birth. No direct complications of the repair procedure were evident, including orthopaedic deformities. Prenatal repair was associated with an increased risk of the women experiencing preterm ruptured membranes and subsequent preterm birth (both before 34 and 37 weeks). Severe maternal illness (infection and need for blood transfusion) were not clearly different; although the review was underpowered to detect any difference in these important, less common outcomes. The included trial was of high quality (low risk of bias) but included a small number of pregnancies. There is currently insufficient evidence to recommend in utero repair for unborn babies with spina bifida.
We searched for randomised and prospective non-randomised trials. Six studies met our inclusion criteria, four are completed and two are still ongoing. An additional study is awaiting classification. The completed studies were conducted between 1997 and 2015 and included 240 participants. One study included children receiving a stem cell transplant and it was stopped early due to safety concerns (six children), the other three studies only included adults, 218 adults with acute leukaemia receiving chemotherapy, and 16 with a blood cancer receiving a stem cell transplant. Three studies were randomised controlled trials and the fourth was a non-randomised study. The haemoglobin threshold of the restrictive strategies varied across the studies. The sources of funding were reported in all four studies. One study was industry sponsored. The evidence is current to June 2016 and is mainly based on adults with acute leukaemia who are having chemotherapy. A restrictive red blood cell transfusion policy may reduce the number of red blood cell transfusions received by an individual. A restrictive red blood cell transfusion policy may have little or no effect on: whether an individual receives a red blood cell transfusion; death due to any cause; bleeding; or hospital stay. We are uncertain whether a restrictive red blood cell transfusion policy affects quality of life, or the risk of developing a serious infection. No studies were found that looked at: adverse reactions to transfusion; development of blood clots; length of stay in intensive care; or need to be readmitted to hospital. There are two ongoing trials (planning to recruit 530 adults) that are due to be completed by January 2018 and will provide additional information for adults with blood cancers. There are no ongoing trials in children. The overall quality of the evidence was very low to low as the included studies were at considerable risk of bias, the estimates were imprecise, and most of the evidence was only for adults with acute leukaemia.
This systematic review of 37 trials showed that routine use of nasogastric tube decompression after abdominal operations, rather than speeding recovery, may slow recovery down and increase the risk of some postoperative complications. On the other hand routine use may decrease the risk of wound infection and subsequent ventral hernia.
This review confirms that folic acid supplementation prevents the first and second time occurrence of NTDs and shows there is not enough evidence to determine if folic acid prevents other birth defects. Information about the safety of other current and alternative supplementation schemes and any possible effects on other outcomes for mothers and babies is also lacking. This review of five trials, involving 7391 pregnancies (2033 with a history of a pregnancy affected by a NTD and 5358 with no history of NTDs), shows the protective effect of daily folic acid supplementation in doses ranging from 0.36 mg (360 µg) to 4 mg (4000 µg) a day, with and without other vitamins and minerals, before conception and up to 12 weeks of pregnancy, for preventing the recurrence of these defects. There were insufficient data to evaluate the effects on other outcomes such as cleft lip and palate, miscarriages or any other birth defects. More research is needed on different types of supplementation programmes and the use of different types of supplements (such as 5-methyl-tetrahydrofolate -5-MTHF), particularly in countries where folic acid fortification of staple foods like wheat or maize flour is not mandatory and where the prevalence of NTDs is still high. The overall quality of the evidence for neonatal outcomes was high for NTDs, whereas, it was of low quality for other neonatal outcomes. The overall quality of the evidence for maternal outcomes was rated as moderate.
We searched for evidence on 30 June 2016 and identified one trial with a small number of women - 48 women were recruited but 46 women (42 pregnancies - 4/46 women did not conceive during the study period) are included in the analysis). The trial took place in Japan and was judged to have a high risk of bias. The trial included women (aged 24 to 40 years) with idiopathic hyperprolactinemia and a history of two to four spontaneous miscarriages; 24 had occult hyperprolactinemia with equal numbers in each group. Women were followed during the study (until the end of the ninth week of pregnancy) and then observed for one year afterwards. In the study, one group of women received a dopamine agonist, bromocriptine (2.5 to 5.0 mg/day until the end of the ninth week of gestation), and the other group of women did not receive any treatment (control group). Evidence from this study showed that the dopamine agonist bromocriptine was effective in preventing future miscarriage (low-quality evidence). However, live birth and conception rates remained similar between women who received bromocriptine and the women who did not receive treatment (very low-quality evidence). The study only reported on serum prolactin levels in the women who were pregnant. The study did not report on any adverse effects that dopamine agonists might possibly have for the women (e.g. nausea, vomiting, headache, vertigo, fatigue, hypotension, arrhythmia, and psychotic symptoms) or her baby (e.g. birth defects, low birthweight, and developmental disabilities). We rated the evidence for the review outcomes of miscarriage as low quality and live birth and conception as very low quality due to questions we had about the study design, the small number of women in the study, and because only one randomized controlled study was identified. Currently, there is not enough evidence (from one small trial) to evaluate the effectiveness and safety of dopamine agonists for preventing future miscarriage in women with idiopathic hyperprolactinemia and recurrent miscarriage history. There is a need for further, high-quality research in this area. Future studies (involving large numbers of women) are needed to expand on the findings of this review. Further studies should examine various dopamine agonists (including bromocriptine, cabergoline and quinagolide) and consider important outcomes (including adverse effects for both the mother and her baby).
We found six studies including a total of 597 people living with vascular dementia. The method of Cerebrolysin treatment differed across studies, with varying strengths of Cerebrolysin and treatment durations. The studies reported that Cerebrolysin had beneficial effects on memory and thinking and on daily functioning. There was no reported risk of side effects with treatment. None of the studies described quality of life of people living with vascular dementia or their caregivers. Although the studies suggested a benefit of Cerebrolysin treatment, the results are not definitive. The included studies had several issues that may have led to misleading results. Even if the benefit reported in the studies is real, the effect was modest and may not be important to people living with dementia. There is a need for a large, well-conducted study to better understand if Cerebrolysin is a useful treatment for people living with vascular dementia.
In summary, therefore, data from the trials included in this review indicate little difference between the effects of these methods, except that women on DMPA are more likely to experience cessation of vaginal bleeding during its use. There was inadequate data to detect differences in some non-menstrual clinical effects, and considering that this contraceptive method remains in use in some countries, further research is indicated.
Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 4 October 2013. The review includes 15 studies published from 1980 to 2012 in which 888 participants were randomised. Eleven of the trials were conducted in Turkey, two in Japan, one in Iran, and one in the UK. Thirteen different interventions were assessed, administered either topically or systemically. Topical interventions: sucralfate, interferon–alpha (different doses), cyclosporin A, triamcinolone acetonide ointment, phenytoin syrup mouthwash. Systemic interventions: aciclovir, thalidomide (different doses), corticosteroids, rebamipide, etanercept, colchicine, interferon–alpha, cyclosporin. There was insufficient evidence to support or refute the use of any included intervention with regard to pain, episode duration or episode frequency associated with oral ulcers, or the safety of the interventions. The quality of the evidence ranged from moderate to very low.
Authors from Cochrane Oral Health carried out this review and the evidence is up to date to 8 March 2018. The review investigated what treatments encourage the tooth to repair by periodontal healing. A total of four studies were included with a total of 183 participants with 257 teeth. One study involved children and young adults, with the other three involving children only. Each study evaluated a different treatment: hyperbaric oxygen, root canal pastes (Ledermix versus Ultracal), removal of the nerve of the tooth (pulp extirpation), and soaking the knocked out tooth in thymosin alpha 1. Each of the interventions aimed to reduce infection or change the inflammatory response or both, at the time of or shortly after the tooth or teeth were replanted. The evidence currently available is insufficient to draw reliable conclusions regarding the superiority of different interventions for knocked out and replanted permanent front teeth. There is urgent need for further well-designed randomised controlled trials. We judged the quality of the evidence to be very low due to problems with the design of the studies.
This systematic review combined the results of eight trials which looked at this question, including a total of 743 participants. Patients taking corticosteroids were three times more likely to experience complete resolution of their sore throat symptoms by 24 hours compared to those taking placebo. In addition, corticosteroids improved the time to onset of symptom relief and the time to complete resolution of symptoms, although the trials were not consistent for these outcomes. Adverse events, relapse rates and recurrence rates were not different for corticosteroid compared to placebo groups. Limitations of the review include the absence of any trials set in Europe and the fact that only two trials addressed the question in children. As all the included trials also gave antibiotics to all participants, we recommend that future research should examine the benefit of corticosteroids in patients who are not also taking antibiotics.
We reviewed 10 randomized clinical trials of which eight were of sufficient quality for inclusion into the analyses. Three trials dealt with acute bronchitis in adults and showed inconsistent but overall positive results for resolution of symptoms (all symptoms, cough and sputum production). For acute bronchitis in children, there were also three studies showing an inconsistent but overall positive combined effect. The available data indicate that the tablet form may be less effective compared to the alcoholic extract. However, the number of trials is not sufficient to prove this. One study each was available for the treatment of acute sinusitis and the common cold in adults. Both showed that the drug was effective in resolving all symptoms including headaches and nasal discharge when taken for an extended time period. Adverse events were more common with P. sidoides, but none were severe. Overall we considered the quality of the evidence low or very low for all major outcomes as there were few studies per disease entity, and all were from the same investigator (the manufacturer) and performed in the same region (Ukraine and Russia). Thus, in summary, there is limited evidence for the effectiveness of P. sidoides in the treatment of ARIs. The evidence is up to date as of April 2013.
The review is current to July 2013 and included 27 trials with 12,835 cases of sore throat. All of the included studies were randomised, placebo-controlled trials which sought to determine if antibiotics helped reduce symptoms of either sore throat, fever and headache or the occurrence of more serious complications. Studies were conducted among both children and adults. The review found that antibiotics shorten the duration of pain symptoms by an average of about one day and can reduce the chance of rheumatic fever by more than two-thirds in communities where this complication is common. Other complications associated with sore throat are also reduced through antibiotic use. The quality of the included studies was moderate to high. However, there were very few recent trials included in the review (only three since 2000), hence it is unclear if changes in bacterial resistance in the community may have affected the effectiveness of antibiotics.
This review included 21 studies in 1490 women and looked at whether one way of teaching, supervising or performing these exercises was better than another. Women who had regular and repeated contact with the person who taught them to do the exercises and monitored their progress were more likely to report they were improved after treatment. Further research is needed because there were problems interpreting the studies, which meant we could not draw any firm conclusions about many of the other possible ways of teaching, supervising or performing these exercises.
Evidence from 19 trials involving 5214 women suggest that supplementation with 601 IU/d or more of vitamin D during pregnancy may reduce the risk of gestational diabetes but may make little or no difference to the risk of pre-eclampsia, preterm birth or low birthweight compared to women receiving 600 IU/d or less. Evidence from 15 trials involving 4763 women suggests that supplementation with 4000 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of pre-eclampsia, gestational diabetes, preterm birth or low birthweight compared to women receiving 3999 IU/d or less. Adverse events were reported differently in most trials; in general, there was little to no side effects reported or similar cases between groups. Supplementing pregnant women with more than the current vitamin D recommendation may reduce the risk of gestational diabetes; however, it may make little or no difference in the risk of the other outcomes. Supplementing pregnant women with more than the current upper limit for vitamin D seems not to increase the risk of the outcomes evaluated. Vitamin D supplementation appears to be safe.
This review found a lack of high-quality evidence to back up any advice on which interventions to use. We examined 41 randomised controlled trials that included 5449 women in early pregnancy. These studies examined the effectiveness of many treatments including acupressure to the P6 point on the wrist, acustimulation, acupuncture, ginger, chamomile, vitamin B6, lemon oil, mint oil, and several drugs that are used to reduce nausea or vomiting. Some studies showed a benefit in improving nausea and vomiting symptoms for women, but generally effects were inconsistent and limited. Overall, studies had low risk of bias related to blinding and reporting on all participants in the studies. However some aspects of the studies were reported incompletely in a way that meant how participants were allocated to groups was unclear and not all results were fully and clearly reported. Most studies had different ways of measuring the symptoms of nausea and vomiting and therefore, we could not look at these findings together. Few studies reported maternal and fetal adverse outcomes and there was very little information on the effectiveness of treatments for improving women's quality of life.
The review includes three trials; one for 12 weeks and two with four-year follow up. We could not combine any data. Trials showed that oral steroids of 1mg/kg to 2 mg/kg (prednisolone equivalent) given every other day seemed to slow the advance of lung disease. However, there are serious adverse effects such as cataracts and the slowing of growth at the higher dose. These led to one trial stopping early. Follow-up data show that catch-up growth started two years after treatment ceased. Treatment must use the lowest effective dose and the shortest duration of therapy to reduce the risk of a permanent effect on growth. A dose of 1 mg/kg on alternate days might be considered for up to 24 months, but close attention should be paid to adverse effects. We do not expect any further trials of this treatment to be undertaken, so we do not plan to continue to regularly update the review. However, if any new information is published, we will include this when it is available. This is an update of a previously published review.
We searched for both published and unpublished trials up to 24 June 2015. We included 10 trials (reported in 9 publications) with 1651 participants that compared NSAIDs with placebo or other drugs. Participants in the trials were 16 to 75 years of age and reported sciatica. The trials followed the participants for a short time, up to three weeks. NSAIDs are no more effective in reducing pain in sciatica than placebo or other drugs. NSAIDs are more effective in overall improvement compared to placebo or other drugs, but this finding should be interpreted with caution as the methodological quality of included trials is low. There is an increased risk of side effects when using NSAIDs compared to placebo. In light of the potentially serious adverse effects associated with NSAIDs, and as this drug is frequently prescribed, high-quality trials in different patient populations are warranted to address the short- and long-term benefits and long-term risks of NSAIDs. The quality of the evidence in this review ranged from very low to low that NSAIDs are more effective than placebo, therefore the results of this review should be interpreted with caution.
This systematic review confirmed the effectiveness of local corticosteroid injection for relief of symptoms for severe carpal tunnel syndrome up to one month after injection. Local corticosteroid injection provides significantly greater clinical improvement compared to oral corticosteroid up to three months after treatment. Two injections of local corticosteroid do not provide significant further clinical improvement of symptoms. Further research is required to determine length of benefit of local corticosteroid injection and benefit for mild and moderate carpal tunnel syndrome.
We searched for evidence on 7 September 2017 and identified three studies (together including 1306 women) comparing intramuscular versus intravenous administration of oxytocin to women during or immediately after the birth of the baby. Studies were carried out in hospitals in Turkey (two) and Thailand (one) and recruited women having only one baby, at term (not early or late). The methods that the studies used to divide women into treatment groups were not clear, and in all three included studies women and staff would have been aware of which treatment they received. This may have had an impact on results and means we cannot be confident in the evidence. The included studies did not report several important outcomes. Only one study reported severe blood loss (a litre or more) after birth and showed that there may be little or no difference between giving intramuscular and intravenous oxytocin. None of the women in one study needed surgery to remove their uterus (womb) after either intramuscular or intravenous oxytocin, and in another study two women needed a blood transfusion, one after intramuscular oxytocin and one after intravenous oxytocin. The quality of the evidence was low or very low, so we had very little confidence in the results. The studies did not report other important outcomes, such as death of the mother, low blood pressure, mothers' dissatisfaction with intramuscular or intravenous oxytocin, and number of babies with jaundice (yellowing of the skin). We found little or no clear difference between intramuscular and intravenous oxytocin for blood loss of 500 mL or more, use of additional drugs to reduce bleeding, and the placenta either not being delivered naturally or having to be removed by doctors. The findings from the three included studies did not clearly show which method of giving oxytocin was better for the mother or baby and more research is needed to answer this question. There was only a small number of included studies and our important outcomes did not occur very often, so there was insufficient evidence to decide whether intramuscular or intravenous oxytocin is more effective and safer for women in the third stage of labour.
This review collates the available evidence from standardised studies for treatment of HCV in dialysis patients and did not include uncontrolled studies. Ten studies all in haemodialysis with about 300 patients showed that standard interferon was effective in producing a short term response which was not sustained and was well tolerated. Pegylated interferon was more effective than standard interferon in producing a short-term response but not a sustained one and both were equally tolerated. Increasing the dose of pegylated interferon did not improve response but was tolerated. Addition of ribavirin to interferon resulted in more treatment discontinuation. Adverse effects of interferons include flu like symptoms, sleep disturbances, decreased appetite, vomiting, diarrhoea or constipation, hair loss and low blood counts. Limitations of this review are that only a few studies were available with few participants, and patients with serious disease were excluded from studies in anticipation of side effects. Hence evidence available was not of high quality.
This review compares the effects of acetylcholinesterase inhibitors alone, or in combination with antipsychotics, compared with antipsychotics alone, or placebo plus antipsychotics. Adding acetylcholinesterase inhibitors with antipsychotics may improve the general psychopathology/negative symptomatology/depressive symptoms in people with schizophrenia. Also, the combination may be useful in improving the attention/reaction time and memory areas of cognition. The major limitation of the results was that most of the studies found were short-term studies. Considering the chronic, severe and enduring nature of schizophrenia, one cannot get a true picture unless well designed long-term studies are done. We hope that this review will highlight the need for more studies in this area.
Current evidence from randomised controlled trials does not support the use of antidepressants. Positive results obtained by antidepressants on mood-related outcomes are consistent with the primary effect of antidepressants. They do not seem to be associated with any effect on dropouts from treatment, cocaine use or side effects, which are direct indicators of cocaine abuse and dependence. A total of 37 randomised controlled clinical studies involving 3551 participants were included in the review. All the studies except one took place in the USA; 33 trials were conducted with outpatients in the community or in mental health centres. In 10 trials patients were also treated for opioid dependence with methadone or buprenorphine. The antidepressants included desipramine, fluoxetine and bupropion and the mean duration of the trials was 10.7 weeks. The included studies utilised 43 different rating instruments and differed in design, quality, characteristics of patients, tested medication, services and the treatments delivered.
Among the pertinent medical literature, only two studies, comprising a total of 80 participants, met the criteria of the methodological quality necessary for their inclusion in this review, although the subsequent quality assessment revealed they scored poorly. Furthermore, the two studies were carried out in USA, with limited generalisability in other geographical/cultural settings. The whole data neither supports nor refutes the effectiveness or cost-effectiveness of VR programs for persons with MS. The data also identified critical points worth of future attention: more awareness of vocational issues by professionals; putting in place practical solutions such as a proper workplace accommodations and employers' education; asking for political/governmental initiatives to really support disabled employees; taking into account that supported withdrawal from work at the proper time is as important as supported re-entering to work. Further research are necessary also to improve the methodology of the researches and to identify those individuals most likely to benefit.
This summary of a Cochrane review presents what we know from research on whether preoperative education improves outcomes (e.g. pain, function) compared with usual care in people receiving hip or knee replacement. After searching for all relevant studies to May 2013, we included nine new studies since the last review, giving a total of 18 studies (1463 participants); 13 trials included 1074 people (73% of the total) undergoing hip replacement, three involved people undergoing knee replacement and two included both people with hip and knee replacements. Most participants were women (59%) and the mean age of participants was within the range of 58 to 73 years Postoperative anxiety (lower scores mean less anxiety): People with hip replacement who had preoperative education had postoperative anxiety at six weeks that was 2.28 points lower (ranging from 5.68 points lower to 1.12 points higher) (4% absolute improvement, ranging from 10% improvement to 2% worsening). - People who had usual care for hip replacement rated their postoperative anxiety score as 32.16 points on a scale of 20 to 80 points. Pain (lower scores mean less pain): People with hip replacement who had preoperative education had pain at up to three months that was 0.34 points lower (ranging from 0.94 points lower to 0.26 points higher) (3% absolute improvement, ranging from 9% improvement to 3% worsening). - People who had usual care for hip replacement rated their pain score as 3.1 points on a scale of 0 to 10 points. Function (lower scores mean better function or less disability): People with hip replacement who had preoperative education had function at 3 to 24 months that was 4.84 points lower (ranging from 10.23 points lower to 0.66 points higher) (7% absolute improvement, ranging from 15% improvement to 1% worsening). - People who had usual care for hip replacement rated their function score as 18.4 points on a scale of 0 to 68 points. Side effects: About 5 fewer people out of 100 had adverse events (such as infection or deep vein thrombosis) with preoperative education compared with usual care but this estimate is uncertain. - 18 out of 100 people reported adverse events with preoperative education for hip replacement. - 23 out of 100 people reported adverse events with usual care for hip replacement. This review shows that in people receiving hip or knee replacement who are provided with preoperative education: There is low-quality evidence suggesting that preoperative education may not improve pain, function, health-related quality of life and postoperative anxiety any more than usual care. Further research is very likely to have an important impact on our confidence in these estimates and is likely to change the estimates. Health-related quality of life, global assessment of treatment success and re-operation rates were not reported. We are uncertain whether preoperative education results in any fewer adverse events, such as infection or deep vein thrombosis, compared with usual care, due to the very low quality evidence.
This review of trials found that BDP delivered with the old and new propellant is effective in helping people with chronic asthma. BDP at all doses improves airflow, reduces symptoms and the need for rescue bronchodilators. The review only included studies conducted for more than 4 weeks. The drug was well tolerated and the safety profile was comparable with placebo. The findings apply to both children and adults. The effects of the new propellant suggest that it could be more effective than the older version, although a different review will address that particular question.
However, previous reviews have found that single session individual interventions and interventions provided to all have not been effective at preventing PTSD. A range of other forms of intervention have been developed to try to reduce psychological distress for individuals exposed to trauma. This review evaluated the results of 15 studies that tested a diverse range of psychological interventions aimed at treating acute traumatic stress problems. There was evidence to support the use of trauma focused cognitive behavioural therapy with such individuals, although there were a number of potential biases in identified studies which means the results should be treated with some caution. Further research is required to evaluate longer terms effects of TF-CBT, to explore potential benefits of other forms of intervention and to identify the most effective ways of providing psychological help in the early stages after a traumatic event.
We therefore conducted a systematic review of the literature, searching key databases for high quality published and unpublished material on the use of adrenaline auto-injectors during episodes of anaphylaxis in the community. We also contacted the relevant pharmaceutical companies to see if they had any such information on the topic. Our searches found many studies relating to anaphylaxis and adrenaline auto-injector use but no randomized controlled trials on this subject. We concluded that the use of adrenaline auto-injectors in anaphylaxis is based on the best available information at present. There is no evidence from randomized controlled trials for the effectiveness of adrenaline auto-injectors in the emergency treatment of anaphylaxis in the community. Such trials would ideally involve comparison of adrenaline with placebo; however, use of a placebo in anaphylaxis treatment would be unethical. We therefore recommend that auto-injectors remain the medication of first choice in the treatment of anaphylaxis in the community.
In this updated review, we have assessed all randomised studies of laparoscopic and open TME for rectal cancer, to compare and combine their results. We included 14 trials reporting on a total of 3528 patients undergoing rectal cancer surgery. In 14.5% of those having laparoscopic surgery needed conversion to open surgery by a large incision in the abdomen due to difficulties or problems during the procedure. There is currently moderate quality evidence that laparoscopic total mesorectal excision (LTME) has similar effects to open TME (OTME) on long term survival outcomes for the treatment of rectal cancer. The estimated effect was imprecise and further research could impact on our confidence int this result. There is moderate quality evidence that it leads to better short-term post-surgical outcomes in terms of length of hospital stay. We found that pain was lower in the LTME group and that resumption of diet was better. We did not find clear evidence of a difference in quality of life between the two groups, but costs were higher for LTME. We await long-term data from a number of ongoing and recently completed studies to contribute to our understanding of the effects of these surgical approaches on long-term disease free, overall survival and local recurrence.
We included studies that used prednisone (or a comparable corticosteroid preparation) at a mean dose of less than or equal to 15 mg per day. We included studies that utilized either placebo controls or active controls (i.e. comparative studies). Very few studies directly assessed the effectiveness of corticosteroids for RA treatment and many were of poor methodologic quality. Only seven of 34 studies identified by our search met criteria for inclusion. Our results indicated that corticosteroids were significantly more effective than placebo controls for four of six outcomes assessed [standardized mean difference for tender joints = -0.37 (95%CI: -0.59, -0.14), swollen joints = -0.41 (-0.67, -0.16), pain = -0.43 (-0.74, -0.12), and functional status = -0.57 (-0.92, -0.22)]. The results for grip strength and ESR were not significant [GS = +0.30 (-0.19, +0.80), weighted mean difference (WMD) for ESR = -7.03 (-18.06, +4.01)]. The single trial that compared prednisone to aspirin indicated no statistically significant difference between these groups for joint tenderness (0.10 (-0.35, +0.55) and for ESR [0.00 (-11.09, +11.09]. Overall, the four outcomes assessed in the single trial that compared prednisone to chloroquine suggested that there was no statistically significant differenece in the effectiveness of these two agents [SMD for joint tenderness = +0.23 (-0.30, +0.75), swollen joints = +0.43 (-0.11, +0.96), functional status = -0.27 (-0.80, +0.26), and WMD for ESR = -16.00 (-30.58, -1.42)].
We found nine studies involving 1244 patients. The studies were often small, used different study designs, and compared fentanyl with many different drugs. Most patients had pain that went from moderate or severe before transdermal fentanyl to no worse than mild pain when using transdermal fentanyl. Only 3 in 10 patients were constipated using transdermal fentanyl compared with 5 in 10 using oral morphine. We could not analyse the data in a meaningful way regarding harmful (adverse) events such as nausea, abdominal pain, gastrointestinal bleeding, and confusion. These events may have been attributable to the underlying disease processes. The effect of the patch can continue after it has been taken off due to medicine that has been taken up by the skin. Used patches need to be disposed of carefully. We could wish for more consistency in study design, and especially in study reporting, which should include the outcome of pain reduced to tolerable levels – no worse than mild pain – so that patients with cancer are not bothered by pain.
We included studies that compared entropy monitoring to the standard practice of administering anaesthetic drugs according to changes in heart rate, blood pressure, tearing, sweating or movement in response to surgery. The evidence is current to September 2014. We included adults and children aged two to 16 years. The participants underwent all types of surgery, except brain surgery, under general anaesthesia. We reran the search in January 2016. We identified one potential new study of interest; we will incorporate it into the formal review findings during the review update. We found 11 studies, with a total of 962 participants. Six studies (383 participants) found minimally shorter time to awakening in the entropy group. No study reported on death occurring in the first 24 hours after surgery or within 30 days to a year after surgery. Eight studies (797 participants) evaluated recollection of intraoperative events (awareness). Adverse events were rare and no benefit was evident. All 11 studies compared anaesthetic medicine use: six compared propofol (given in the vein) and five evaluated anaesthetic gas (sevoflurane or isoflurane). Limited studies were analysed because of differences in methodology and units of measurement. Analysis of three studies (166 participants) found reduced propofol use, and two studies (156 participants) found lower sevoflurane use in the entropy group. No study reported on cost of general anaesthesia. Three studies found shorter length of stay in the postanaesthesia care unit (PACU) in the entropy group. The evidence for assessing reduction in time to awakening, recall of intraoperative events and amount of inhalation of anaesthetic agents used is of moderate quality. The quality of evidence as regards intravenous anaesthetic agent used and length of stay in the PACU is of low quality.
We reviewed studies that compared psychological interventions to treatment as usual groups who either received no treatment, or were on a waiting list for treatment or received usual care. We found eight studies, which together suggested that cognitive and/or behavioural treatments were better than treatment as usual conditions at reducing clinical symptoms. Baseline OCD severity and depressive symptom level predicted the degree of response. However, the conclusions were based on a small number of randomised controlled trials with small sample sizes. There were no trials of other forms of psychological treatment such as psychodynamic therapy and client-centred therapy, and a lack of available evidence for the long-term effectiveness of psychological treatments.
We included 9 randomised controlled trials, with a total of 363 participants. No studies examined surgical methods. Photodynamic therapy appears to be an effective treatment and has the benefit of minimal scarring compared with cryotherapy or 5-fluorouracil. Cryotherapy is convenient and less expensive, but does not appear to be as effective as photodynamic therapy and results in more scarring; 5-aminolevulinic acid with photodynamic therapy (ALA-PDT) appears to be more effective than 5-fluorouracil, whereas methyl aminolevulinate with photodynamic therapy (MAL-PDT) does not appear to be as good as 5-fluorouracil. One study demonstrated benefit with imiquimod cream. Specific recommendations cannot be made from these data, so this review cannot give firm conclusions about the comparative effectiveness of treatments. There is a clear need for future research to focus on a range of different studies comparing various therapies with each other, and in particular to surgical treatments to provide high-quality evidence to guide clinical practice. The age group, number and size of lesions, sites affected, and immunological status may all influence therapeutic choices. Longer-term follow up (up to 10 years) is needed to determine the effect of treatments on risk of progression of lesions of Bowen's disease to squamous cell carcinoma.
We identified 45 trials (involving 1619 participants) up to January 2018 and included them in our review. Twenty-four different electromechanical devices were described in the trials, which compared electromechanical and robot-assisted arm training with a variety of other interventions. Participants were between 21 to 80 years of age, the duration of the trials ranged from two to 12 weeks, the size of the trials was between eight and 127 participants, and the primary outcome (activities of daily living: the most important target variable measured) differed between the included trials. Electromechanical and robot-assisted arm training improved activities of daily living in people after stroke, and function and muscle strength of the affected arm. As adverse events, such as injuries and pain, were seldom described, these devices can be applied as a rehabilitation tool, but we still do not know when or how often they should be used. The quality of the evidence was high.
We searched for randomised controlled trials (experiments that randomly allocate participants to one of two or more treatment groups) looking at the effectiveness of exercise-based rehabilitation programmes compared with no exercise, or a different type or intensity of exercise, in people aged 18 years or over, who were heart transplant recipients. We included 10 trials that studied 300 people who were heart transplant recipients. Nine studies compared exercise with no exercise; one study compared high-intensity interval training with continuous moderate-intensity exercise. We found that exercise-based cardiac rehabilitation led to an increase in the exercise capacity of heart transplant recipients compared to not undertaking exercise. There was evidence of better exercise capacity following high-intensity interval training compared to continuous moderate-intensity exercise. Four studies reported health-related quality of life, but there was no evidence of differences between exercise training and no exercise training in most (18/21) aspects reported, or between high- and moderate-intensity exercise. One adverse event was reported in one study. Risk of bias in the included studies was assessed as low or unclear; lack of reporting made assessment for more than half of included studies challenging. Six (of 10) trials reported sources of funding. None reported funding from agencies with commercial interests in the results. Poor reporting or few participants in the analyses led to evidence quality being judged as moderate for both exercise capacity and health-related quality of life. Evidence suggested that exercise-based cardiac rehabilitation improves exercise capacity, and that exercise has no impact on health-related quality of life in the short-term (median 12 weeks follow-up), in heart transplant recipients whose health is stable. Further research is needed to establish long-term impacts of exercise-based rehabilitation on important aspects such as risk of death and hospital admission.
This evidence is current to June 2017. We included 13 studies with 2001 participants with CS or LCOS as complications of myocardial infarction, heart failure or cardiac surgery, with follow-up periods between the length of the recovery period up to 12 months. Four studies were funded by a drug manufacturer. We compared different approaches to standard therapies with possible addition of inotropic or vasoconstrictive drugs as levosimendan, dobutamine, enoximone, epinephrine. This review presents low-quality evidence that levosimendan compared to dobutamine reduces short-term mortality. The survival benefit with levosimendan vs. dobutamine is not confirmed on long-term follow up. Very low-quality evidence shows uncertainty around the effect of levosimendan compared to placebo or enoximone. Very low-quality evidence shows uncertainty on the comparison of epinephrine with norepinephrine-dobutamine, amrinone or enoximone with dobutamine, dopexamine with dopamine, and nitric oxide with placebo. We have reduced confidence in the results of the studies that we analysed (low- or very low-quality evidence) due to serious study limitations, very serious imprecision or indirectness.
The review identified 10 trials that involved 2412 participants. Overall, the quality of the trials was not high but the review showed that stockpiles of the vaccines maintained their effectiveness even when diluted. New second-generation vaccines seemed to be effective but still have adverse events. There were too few participants overall to be able to assess rare outcomes. Further research is needed, particularly on the third-generation vaccines.
There was not enough information to work out whether azapirones are any more or less effective than placebo in causing substantial improvements in panic disorder overall. A small amount of moderate-quality evidence suggests that the acceptability of azapirones for panic disorder is lower than for placebo. There was not enough information to compare any differences in adverse effects caused by azapirones and placebo. Studies with larger sample sizes and fewer risks of bias should be carried out. Studies should report how participants were allocated to each treatment, and whether the trials were financially sponsored by the manufacturer of the drug. Study protocols should be registered to avoid selective reporting of outcomes by authors. Trials need to test azapirones other than buspirone to determine their effectiveness. Remission or response should be reported as the efficacy outcome and longer-term outcomes need to be addressed to establish whether the effect is transient or durable. Trials should better report any harms experienced by participants during the trial.
The evidence is current up to March 2014. We identified 27 studies and included the outcomes of 1976 participants. Studies investigated the outcomes of patients undergoing planned surgical procedures on the abdomen (18), the bones or joints (4), the heart (4) or the thyroid gland (1). Eighteen studies compared carbohydrate supplements versus an identical appearing placebo drink that did not contain carbohydrates; in six of these studies, an additional group of patients had nothing to eat or drink for at least six hours before surgery. In nine studies, taking carbohydrate supplements was compared with having nothing to eat or drink for six hours before surgery. The primary outcomes of length of hospital stay and complication rate were reported by 19 and 14 studies, respectively. Patients given carbohydrates before planned surgical procedures went home between 0.04 and 0.56 days sooner than those receiving a placebo drink or having nothing to eat or drink before surgery. Carbohydrate supplements had little or no effect on complication rate or on how people feel in-hospital during recovery from surgery. The overall quality of the evidence varied from very low to high. The quality of evidence in support of carbohydrate supplements resulting in a shorter hospital stay was very low because the included studies had important flaws in their design, a very wide range of results was described and evidence revealed that studies showing no differences in length of hospital stay may not have been published. When we looked only at well-conducted studies, we found that carbohydrate supplements had little or no effect on length of hospital stay. The quality of evidence to support the effects of carbohydrate supplements on complication rate was low because issues with study design were identified and results were not similar across studies.
Study characteristics: The evidence is current to December 2016. We included in this review 25 randomized controlled trials involving 3278 participants. Studies included both adults and children. Fifteen of the included trials used self-reporting of pain intensity by trial participants to determine the effectiveness of local anaesthetics. Key results: Study results suggest that directly applying local anaesthetics to the skin is an effective, non-invasive way of providing pain control during suturing or stapling of skin lacerations. Study findings on the efficacy of individual topical anaesthetics were limited by study design, and data on the efficacy of each topical agent were obtained mostly from single trials. Researchers reported no serious side effects following the use of cocaine-containing or cocaine-free topical anaesthetics. The overall broadly comparable effectiveness of cocaine-free topical anaesthetics for skin laceration repair brings into question the necessity to include cocaine as a component of local anaesthetic solutions. The small number of trials in each comparison group and the range of outcome measures assessed prevented pooling and quantitative analysis of data for all but the single outcome of pain intensity. Additional studies are necessary to directly compare the effectiveness of different formulations of topical anaesthetics. Our review was limited to pain control for repair of superficial lacerations, and our results might not be generalizable to deeper lacerations or more complex procedures performed on intact skin. Further research is needed to strengthen the evidence and to overcome the weakness of the included studies. Quality of the evidence: The overall quality of the evidence was low owing to limitations in study design, ways that studies were carried out (implementation), imprecision of results and high probability of selective data reporting. Most of the trials that compared infiltrated and topical anaesthetics were at high risk of bias, and this was likely to influence measured effects.
The studies suggested that CHM used either on its own or with antibiotic treatment may be more effective than antibiotics alone for relieving acute UTIs and preventing recurrent episodes. There were only two studies that explicitly stated that adverse events were to be reported; neither reported any adverse events. However, studies were small and assessed as having poor methodological quality; and most study participants were post-menopausal. Therefore, results should be interpreted cautiously and can only be considered as preliminary findings that may not be relevant to pre-menopausal women. Further research is required to provide more rigorous evidence before CHM can be routinely recommended as a treatment option for recurrent UTIs.
The review of scientifically well conducted trials found that taking oral oestrogen or combined oestrogen and progestogen hormone replacement therapy greatly reduces the frequency and severity of these symptoms. This effect was significantly greater than the reduction of symptoms seen with placebo (dummy tablets) over time. No adverse effects were found but as the trials were only short term, more research is needed.
Our search for studies retrieved 283 articles. Of these, five trials comprising 233 tinnitus patients met our inclusion criteria and were included in the review. The first study considered the use of 'complex waveform rTMS', the second looked at the use of high-frequency rTMS, and the other three studies considered the use of low-frequency rTMS. We found that the use of low-frequency rTMS resulted in 'partial improvement' in tinnitus severity and disability in one study, however these results were not replicated in two other studies that considered rTMS at the same frequency. Furthermore, this single positive finding should be taken in the context of the many different variables which were recorded at many different points in time by the study authors. We were able to demonstrate an improvement in tinnitus loudness in patients undergoing rTMS when we combined the results of two other studies. rTMS is a safe treatment for patients with tinnitus in the short-term, however no data were available to verify safety in the long-term.
One small trial confirms that compression reduces ulcer recurrence compared with no compression. There is some evidence that people wearing high rather than moderate-compression hosiery are less likely to get a new ulcer. It is not clear whether moderate strength hosiery is better tolerated than high compression. There is, therefore, some evidence that compression hosiery might prevent ulcers, but the evidence is not strong.
Reviewers found only one controlled trial of moderate methodological quality (most recent search, 14 June 2018). This trial had a cross-over design, and each of the 10 participants had three seemingly identical prosthetic weights added to the prosthesis below the knee in random order. All artificial limbs were modular-style prostheses. The participants - nine men and one woman - were over 50 years of age, and eight were over 60 years old. Over the few hours of the trial, four participants preferred the lightest weight (150 g), five preferred the medium weight (770 g), and one preferred the heaviest weight (1625 g). Seven of the 10 people successfully ranked the weights from lightest to heaviest. The weights did not alter participants' walking speed in a two-minute walk test. Study authors reported no adverse effects. The inclusion of only one trial with a small number of participants, short exposure to different weights in a laboratory setting, and the fact that there were differences in weight between people and their prostheses limit the usefulness of these findings. The limited evidence included in this review is of very low quality and is insufficient to inform the choice of prosthetic rehabilitation, including optimum weight of the prosthesis, after unilateral transfemoral amputation in older dysvascular people.
This review focuses on the effectiveness of carbamazepine for people with schizophrenia. A search of the Cochrane Schizophrenia Group's trials register was carried out July 2012. Ten studies were found with 283 people. Carbamazepine was compared with no active medication (‘dummy’ or placebo treatment), versus an antipsychotic or when taken in addition to an antipsychotic. However, all of the 10 studies were small and information in them was of a poor standard. There is therefore a lack of evidence whether carbamazepine reduces symptoms and side effects in people with schizophrenia or similar mental health problems. Larger well-designed trials are necessary to provide stronger evidence before carbamazepine can be recommended as a treatment for people with schizophrenia. This plain language summary has been written by a consumer Ben Gray: Service User and Service User Expert. Rethink Mental Illness.
We found 12 studies involving 10,953 residents in 355 care homes in ten countries that evaluated interventions to optimise prescribing for care home residents. Most of the interventions had several components, often involving a review of medicines with a pharmacist and doctor. Some interventions included a teaching component and one study used Information Technology (IT). We found no evidence of benefit of the interventions with respect to reducing adverse drug events (harmful effects caused by medicines) or death. One study led to residents having fewer days in hospital; however, the majority of studies did not show a benefit in relation to reducing hospital admissions. One study led to a slower decline in health-related quality of life. Problems relating to medicines were found and addressed through the interventions used in the studies. Prescribing was improved based on criteria used to assess the appropriateness of prescribing in five studies. We judged the overall quality of the evidence for the reported outcomes to be low for adverse drug events (harmful effects caused by medicines), hospital admissions, death, quality-of-life, medication-related problems, medication appropriateness, and very low for the cost of medicines. More high-quality studies need to be done to gather more evidence for these and other types of interventions. Further studies are needed to evaluate new technologies, including computer systems that support prescribing decisions. More work needs to be done to make sure that researchers are consistently measuring outcomes that are important to care home residents.
We searched eight electronic databases and three trials registers (in October 2012 for all except Embase, which was searched in August 2012). We also searched the reference lists of relevant papers and contacted nutrition-related organisations and researchers in this field. We found eight relevant randomised controlled trials, enrolling 10,037 children under five years of age. All but one study was conducted in Africa. The risk of bias in the studies was generally low, though two studies had a high dropout rate. The participants were aware which intervention group they were in and this may have influenced their behaviour but we thought it unlikely it would have influenced the results since the outcomes measured were objective ones. For four of the studies, we were unable to assess if the study authors reported all the outcomes they intended to measure. When any type of specially formulated food was compared to standard care (medical care and counselling without foods), the children treated with foods had a higher chance of recovering from moderate malnutrition (two studies), greater improvement in nutritional status (two studies), and a lower number of dropouts (one study). A reduction in mortality was not shown. When lipid-based nutrient supplements (which are food with high energy density and high lipid content) at full dose were compared to blended foods at full dose (which are dry food mixtures without high lipid content), there was no difference between these two types of foods in terms of number of deaths (five studies), children progressing to severe acute malnutrition (three studies), and children dropping out (four studies). However, lipid-based nutrient supplements increased the number recovered by 10% (five studies), decreased the number of children non-recovering (three studies), and slightly improved the nutritional status among the recovered. One study observed more children vomiting when given lipid-based nutrient supplements compared to blended foods, but this was not reported by the other studies. No other side effects were reported. Few studies evaluated foods at complementary dosage (i.e. foods given in low quantity, just to complement the diet and not to fully substitute it), and no conclusion could be drawn from these studies. When specific foods were compared to each other, a type of corn-soy blended food called CSB++ compared to lipid-based nutrient supplements resulted in similar outcomes, while results of another blended food (CSB pre-mix) versus lipid-based nutrient supplements were unclear. In one study, CSB++ did not show any significant benefit over locally-made blended foods, for example, Misola. No study evaluated the impact of improving adequacy of local diet, such as local foods prepared at home according to a given recipe or of home processing of local foods (soaking, germination, malting, fermentation) in order to increase their nutritional content. In conclusion, there is moderate to high quality evidence that both lipid-based nutrient supplements and blended foods are effective in treating children with moderate acute malnutrition. Although lipid-based nutrient supplements (LNS) led to a clinically significant benefit in the number of children recovered in comparison with blended foods, LNS did not reduce mortality, the risk of default or progression to SAM. It also induced more vomiting. Blended foods such as CSB++ may be equally effective and cheaper than LNS. There are no studies evaluating special recipes to improve the adequacy of the usual home diet, an approach that should be evaluated in settings where food is available, and nutritional education and habits are the main determinants of malnutrition. There are no studies from Asia, where moderate acute malnutrition is most prevalent.
We searched for evidence on 5 February 2018. We identified 21 randomised controlled trials from which 11,246 mother-baby pairs contributed results for this review. Examples of the additional social support include information, home visits, telephone calls and stress management. The overall quality of evidence for most outcomes was moderate. It was not possible to blind women to which group they were in. We found that women who received additional social support during pregnancy may be slightly less likely to have a baby with low birthweight (16 studies, 11,770 babies), or give birth too early (14 studies, 12,282 babies). The number of babies that died around the time of birth was similar for both groups of women (15 studies, 12,091 babies). Women who received the additional social support were, however, probably less likely to be admitted to hospital during their pregnancy (4 studies, 787 women), or to have a caesarean birth (15 studies, 9550 women). Women with additional social support may be less likely to be depressed (1 study, 1008 women). Findings around satisfaction with care were mixed, with one study reporting the support group being more satisfied, whilst another study suggested women in the usual care group were more satisfied. The findings did not appear to be different if the social support was provided by trained lay people or health professionals. Although programmes that offer additional social support during pregnancy are unlikely to prevent the pregnancy from resulting in a low birthweight or early birth, before 37 weeks of pregnancy, they may be helpful in reducing the likelihood of antenatal hospital admissions and the need for caesarean births. Additional social support is not powerful enough to improve the outcomes of the pregnancy during which it is provided, as measured by the outcomes considered in this review. The factors contributing to deprivation require social change in order to bring about improvements in health for mothers and their newborn babies.
The evidence is current to January 2018. We included seven studies, recruiting 493 patients. The participants were adults having septoplasty in all of the included studies and the percentage of females ranged from 20.7% to 58.3%. Two studies, recruiting 142 participants, assessed local anaesthetic injection. Four studies, recruiting 301 participants, used nasal packing postoperatively and assessed the addition of a local anaesthetic to the nasal pack. One study, recruiting 50 participants, assessed a regional nerve block. No studies were funded by the anaesthetic drug manufacturer. Local anaesthetic injection compared to no treatment/placebo The main outcome we looked at was the effect on reducing pain at 12, 24 and 48 hours postoperatively. Two studies assessed local injection of anaesthesia, but neither reported on pain at these times. It is unclear whether local injection increased postoperative vomiting. Neither study reported uncontrollable postoperative bleeding. Local anaesthetic application via nasal packing compared to no packing/packing with placebo Four studies that used nasal packing after the operation assessed the addition of a local anaesthetic to the pack compared to packing with a placebo added. Four of these studies reported pain at 12 or 24 hours (or both) postoperatively. Local anaesthetic added to nasal packing reduced pain by 17.0 points on a 100-point scale at 12 hours postoperatively and by 7.5 points at 24 hours postoperatively. These studies did not report on pain at 48 hours postoperatively. Local anaesthetic application by nasal packing decreased the need for additional analgesia (painkillers) postoperatively. No studies reported postoperative vomiting or uncontrollable postoperative bleeding. No studies evaluated local anaesthetic application via nasal packing compared to no packing. Regional nerve block compared to no treatment/placebo One study compared a regional nerve block with no treatment, but this study did not report postoperative pain or any of our other outcomes. We graded the quality of evidence for the use of local anaesthetic injection as low, which means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. We downgraded the quality of the evidence because of the small number of patients and events. We graded the quality of evidence for the use of local anaesthetic applied to nasal packing as low at 12 hours postoperatively and very low at 48 hours. We downgraded the quality of the evidence because of the poor conduct of the studies and because the results were not similar across studies. We did not grade the quality of evidence for the use of regional nerve block because none of our review outcomes were reported by the one study looking at this. The addition of local anaesthesia to nasal packs (if these are being used) following septal surgery may reduce postoperative pain within the first 12 hours postoperatively compared to nasal packing with a placebo added. However, our review revealed a lack of evidence on which to base comparisons of the various types of local anaesthesia. This review should prompt further research comparing local anaesthesia by injection, as an addition to nasal packing and as a regional nerve block following septal surgery.
We searched the literature in April 2014 and found 45 randomised controlled trials for this update of the review. We analysed data from 4696 participants who received treatment for their fatigue. The trials dealt with neurological diseases (such as multiple sclerosis (753 participants), post-polio syndrome (58) and Parkinson's disease (19)), different types of cancer (3223), HIV/AIDS (514), end-stage renal disease (56), multi-type advanced disease in hospice patients (30), amyotrophic lateral sclerosis (28) and end-stage chronic lung disease (15). There was weak evidence for the efficacy of amantadine, pemoline and modafinil in reducing fatigue in patients with multiple sclerosis. There was also weak evidence for the efficacy of carnitine and donepezil for cancer-related fatigue. One small trial showed that people with HIV/AIDS and fatigue seemed to benefit from treatment with methylphenidate or pemoline. There was some low-quality evidence from small trials that methylphenidate, a stimulant drug that improves concentration, is effective for the management of cancer-related fatigue. There was no information about dexamphetamine, paroxetine or testosterone. Previous studies have shown that erythropoietin and darbepoetin, drugs that improve anaemia (a shortage of red cells or haemoglobin in the blood), are also effective for cancer-related fatigue. However, due to safety concerns and side effects shown by more recent studies, erythropoietin and darbepoetin should no longer be used. Therefore, we excluded these drugs from this review update. Overall, most side effects of the investigated drugs seemed to be mild. Based on limited evidence from small studies, the evidence does not support the use of a specific drug for the treatment of fatigue in palliative care. Future trials should measure fatigue in advanced disease using comparable and standardised measures.
We searched for randomised studies up to 28 October 2016. We looked at whether insertion of contraceptive implant soon after childbirth or when women come back for the first postpartum check-up affected use of this contraception method. We included three studies with a total of 410 women. Use of a contraceptive implant was higher when it was applied right after childbirth than when it was applied four to six weeks later. There appeared to be little or no difference between the groups in the continuation rate of contraceptive implant use at 6 months. It was unclear whether there was any difference between the groups in continuation of contraceptive use at 12 months or in the unintended pregnancy rate at 12 months. Although vaginal bleeding and other adverse effects in the first six weeks after birth including nausea, hair loss, hirsutism, headache, and acne seem to be higher in women that receive this method a few days after childbirth rather than four to six weeks later, this finding however cannot be definitely concluded as all participants knew the nature of the intervention they received (were not blinded) and the reports of these adverse effects were not objectively assessed. It was unclear whether there was any difference between the groups at 12 months in heavy, irregular vaginal bleeding or associated severe cramping, rates of unintended pregnancy, or in measures of participants' satisfaction. Nor was it clear whether there was any difference in breastfeeding rates at 6 months. The included studies were conducted in the USA, and generalisation of these findings to other population or settings should be applied with caution. Overall, the quality of the evidence was moderate to very low. The main limitations were imprecision and risk of bias (related to lack of blinding and to attrition). Further good quality, well-designed randomised controlled trials will provide additional information.
The review identified seven trials involving 8013 women. Fetal pulse oximetry plus CTG showed no difference in caesarean section rates overall, nor any difference in the mother's or newborn's health, compared with CTG alone. If there was concern about the baby's well-being before the fetal pulse oximetry probe was placed, the use of fetal pulse oximetry reduced caesarean sections performed for the baby's well-being. The one trial of oximetry with CTG compared with CTG and fetal ECG showed an increase in the caesarean rate in the oximetry group. In two of the trials, the company making the fetal pulse oximetry machines provided some funding. A better method than fetal pulse oximetry is needed for checking on the well-being of the baby during labour.
This review included eight trials (10 papers) which covered the process of risk assessment for familial breast cancer. These focused on the psychosocial impact on patients, as well as other outcomes and aspects of service delivery, and provided data on 1973 participants. Due to the limited number of trials, this review found insufficient evidence to make any firm conclusions about the best way to deliver risk-assessment services for individuals concerned about a family history of breast cancer. All eight included studies did, however, demonstrate improvements in psychological well-being and a decrease in the levels of cancer worry as a result of the risk-assessment service. Although limited, the findings of this review suggest that cancer genetic risk-assessment services can help to reduce distress, improve the accuracy of the individual's perceived risk of breast cancer, and increase knowledge about breast cancer and genetics. Existing evidence suggests that such services do not cause patients any harm and, in the short-term, can have a positive effect by helping to ease distress and decrease cancer worry. From this review, it does not appear that the health professional delivering the risk assessment has a significant impact on these outcomes.
Only randomised controlled trials were included in this review. These were studies where two groups of patients were compared, one group had speech and language therapy, the other did not receive any therapy intended to improve speech. The patients were assigned to each of the groups in a random fashion so as to reduce the potential for bias. Three trials with a total of 63 patients were found comparing speech and language therapy with an untreated group. The quality of the methods used in these trials was variable, with all studies failing in at least one critical area. All three of the controlled trials reported a positive effect of speech and language therapy for speech disorders in Parkinson's disease. Many of the outcome measures examined appeared to improve by a clinically significant amount after therapy. However, it should be noted that there were flaws in the methods used in these studies and only a small number of patients with Parkinson’s disease were examined. This means that there is insufficient evidence to absolutely prove or disprove the benefit of speech and language therapy for the treatment of speech disorders in Parkinson's disease patients, but lack of evidence does not mean lack of effect. A large well designed placebo-controlled randomised trial is needed to assess the effectiveness of speech and language therapy for speech disorders in Parkinson's disease. Outcome measures with particular relevance to people with Parkinson’s disease should be chosen and the patients followed for at least six months to determine the duration of any improvement.
We looked for studies that included smokers and provided or offered medication to everyone. People in the studies were then randomly split into groups which received different amounts or kinds of behavioural support. To assess whether the support given helped people to quit, the studies had to count the number of people not smoking after six months or more. We did not look at studies that only included pregnant women. We searched for studies in June 2018. We included 83 studies, with almost 30,000 people. Most studies included people who wanted to quit smoking, but a small number of studies offered support to people who were not trying to quit. Combining results from 65 trials suggested that increasing the amount of behavioural support for people using a stop-smoking medication increases the chances of quitting smoking. About 17% of people in the groups receiving less or no support quit smoking, compared to about 20% in the groups receiving more support. Providing some support via personal contact, face-to-face or telephone, is helpful. Few studies compared different types of support. More research is needed to find out if some types of behavioural support help more people using medication to quit smoking. We judged the overall quality of evidence to be high, meaning further research is very unlikely to change our results. This review has been updated twice and both times the findings remained very similar, even though many new studies were added.
This review identified five studies that included a total of 333 participants. Two studies compared methotrexate (administered by pill or intramuscular injection) to a placebo (a sugar pill or a saline injection). One of these two studies also compared methotrexate to 6-mercaptopurine (an immunosuppressive drug). One small study compared methotrexate to both 6-mercaptopurine and 5-aminosalicylic acid (an anti-inflammatory drug). Two studies compared combination therapy with methotrexate and infliximab (a biological drug that is a tumour necrosis factor-alpha antagonist) to infliximab used by itself. One high quality study (76 patients) shows that methotrexate (15 mg/week) injected intramuscularly (i.e. into muscles located in the arm or thigh) for 40 weeks is superior to placebo for preventing relapse (return of disease symptoms) among patients whose disease became inactive while taking higher doses of intramuscular methotrexate (25 mg/week). Side effects occurred in a small number of patients. These side effects are usually mild in nature and include nausea and vomiting, cold symptoms, abdominal pain, headache, joint pain and fatigue. One small study (22 patients) found no difference in continued remission between low dose methotrexate (12.5 mg/week) taken orally and placebo and suggests that low dose oral methotrexate is not an effective treatment for inactive Crohn's disease. However this result is uncertain due to the small number of patients assessed in the study. Large-scale studies of methotrexate given orally at higher doses for maintenance of remission in Crohn’s disease may provide stronger evidence for the use of methotrexate in this manner. A pooled analysis of two studies (50 patients) found no difference in continued remission between oral methotrexate (12.5 to 15 mg/week) and 6-mercaptopurine (1 mg/kg/day). No firm conclusions can be drawn as these results are uncertain due to poor study quality and small numbers of patients. A small study (13 patients) found no difference in continued remission between methotrexate and 5-aminosalicylic acid. No conclusions can be drawn from this study as the results are very uncertain due to poor study quality and small numbers of patients. A pooled analysis of two studies (145 patients) found no difference in continued remission between combination therapy and infliximab. Combination therapy with methotrexate and infliximab does not appear to be any more effective for maintenance of remission than infliximab used by itself. This result is uncertain because one study was of poor quality (the other was high quality) and small numbers of patients.
The four clinical trials included 2818 participants who were randomly allocated to undergo either TAVI or surgical aortic valve replacement (SAVR). The trials were multicentre and took place in Australia, Canada, France, Japan, the Netherlands, New Zealand, the USA, Denmark, and Sweden. Moderate-certainty evidence from clinical trials shows that, in the short term (i.e. during hospitalisation and up to 30 days of follow-up), there is probably little or no difference between TAVI compared with SAVR in risk of death due to any cause, stroke (insult to the brain), myocardial infarction (injury or death of heart muscle), or death due to cardiac causes (e.g. myocardial infarction or failure of the heart muscle pump). Low-certainty evidence shows that TAVI may reduce the risk of rehospitalisation compared with SAVR. We are uncertain whether TAVI, compared with SAVR, affects the length of hospital stay, although it appears to be associated with shorter duration of hospitalisation. High-certainty evidence shows that fewer people had atrial fibrillation (a type of irregular heart rhythm), acute kidney injury (insult to the kidney), and bleeding when they underwent TAVI, compared with SAVR. However, moderate-certainty evidence shows that TAVI probably increases the risk of permanent pacemaker implantation (a device that is placed to artificially set the heart rhythm), compared with SAVR. We consider the overall quality of evidence to be moderate for most relevant outcomes (death, stroke, myocardial infarction, cardiac death, and risk of permanent pacemaker implantation), with the exception of rehospitalisation (low-quality evidence) and length of hospital stay (very low quality evidence). The evidence for atrial fibrillation, acute kidney injury, and bleeding was of high quality.
The review found that lipid formulations of amphotericin B had fewer adverse effects (less nephrotoxicity and fewer dropouts) than conventional amphotericin B. However, it is not clear whether there are any advantages of these formulations if conventional amphotericin B is administered under optimal circumstances.
We carried out a wide database search to look for studies of interventions for the management of breathing problems in children with severe neurological impairment. We found 15 studies of interest, which included a number of different types of treatment. The results showed that several different treatments provided potential benefits, and for most interventions no serious adverse effects were reported. However, the quality of the studies was not good enough to inspire confidence in the findings. Night-time positioning equipment and spinal bracing were shown to have a potentially negative effect in some participants. Although some studies looked at the same type of treatment, they used it in different ways or used different measures to assess effectiveness, so we could not put the results together. Of the 15 studies included here, only four used the 'gold standard' study design for health interventions. The remainder of the studies used less robust study designs, which limits the strength of the results. Further well-designed randomised studies including larger numbers of participants are required to guide healthcare professionals to select the most effective treatments.
This review identified 28 randomised controlled trials undertaken in 4287 women. Most of the women knew which treatment they were receiving, which may have influenced their judgements about menstrual blood loss and satisfaction. Other aspects of study quality varied among trials. Evidence is current to May 2018. Nineteen of the 28 trials acknowledged that they received funding, supplies of equipment, or technical assistance from the pharmaceutical industry and from equipment manufacturers. Moderate- to very low-quality evidence suggests that first- and second-generation approaches were equally effective in the treatment of HMB. Newer (second-generation) treatment approaches were safer in terms of rate of fluid overload, cervical lacerations, and haematometra, with similar rates of uterine perforation. The newer approaches (second-generation ablation) were quicker and were more likely to be done under local (rather than general) anaesthesia compared with first-generation approaches. Most women in both groups were satisfied with results of the procedure. Not enough evidence is available to show which second-generation approaches are superior to others, and information about third-generation approaches is not available for comparison. Evidence ranged from moderate to very low quality. Few studies were blinded, data were limited, and heterogeneity was substantial for some outcomes, leading to downgrading of the quality of evidence.
We identified 18 relevant trials, involving 633 participants which evaluated this type of therapy, up to September 2014. Treadmill training did improve gait speed, and stride length; but walking distance and cadence did not improve. Acceptability of treadmill training for study participants was good and adverse events were rare. It seems that such devices could be beneficial and could be applied in routine rehabilitation. However, it is still not clear when and how often they should be used and how long a benefit lasts. The quality of this evidence for the primary outcomes was moderate to low. Adverse events were not reported in studies and drop outs did not occur more frequently in people receiving treadmill training. Also we investigated only gait parameters, improvements of activities and/or quality of life were not investigated.
There is a lack of studies to determine the best CSF dose for children and only a small number of RCTs evaluating the role of CSF in children's ALL. The prophylactic administration of CSF reduces hospital stay, and risk of infections. The authors did not find evidence that CSF reduces febrile neutropenia episodes, their duration, or treatment delays in children with ALL undergoing chemotherapy. Follow up was too short to provide useful information on any possible effect on relapse or survival.
In this review of 26 randomised controlled trials of 2959 women, the effectiveness and safety of inhaled analgesia as pain relief for women in labour were studied. It was found that inhaled analgesia may help relieve pain during labour but women have to be informed about the side effects, such as nausea, vomiting, dizziness and drowsiness. Inhaled analgesia may help relieve labour pain without adversely increasing operative delivery rates (forceps or vacuum extraction, caesarian section), or affecting neonatal well being. Flurane derivatives were found to be slightly more effective than nitrous oxide for the reduction of pain and for pain relief although nitrous oxide also helped to relieve pain when compared with no treatment. Women who used nitrous oxide were more likely to experience nausea compared with flurane derivatives. When nitrous oxide was compared with no treatment or placebo, nitrous oxide resulted in side effects such as nausea, vomiting, dizziness and drowsiness. There was no information for satisfaction with childbirth experience or sense of control in labour in these studies and further research on these two important outcomes would be helpful.
A newer treatment called cinacalcet showed promise for improving abnormal mineral levels but the effects of this drug on patient outcomes (the way patients feel function and survive) were unclear from early studies. We have updated an earlier review dated 2006 to include studies that assessed the effects of cinacalcet in about 7500 people with chronic kidney disease. While cinacalcet improves some blood abnormalities, it does not improve risk of death or heart disease in people treated with dialysis. In addition, people who take cinacalcet may experience increased nausea, vomiting and the need for blood tests to check blood calcium levels. The current research is high-quality and means that additional new studies are unlikely to change our confidence in these results. Information for the use of cinacalcet in people with milder forms of kidney disease and those with a kidney transplant is insufficient to guide decision making.
In September 2016 we searched for clinical trials in which antidepressants were used to treat chronic nerve, menstrual, muscular, joint, or stomach pain. We found four trials with a total of 272 participants (aged 6 to 18 years old) who had nerve pain, general painful inflammation, stomach pain, or irritable bowel syndrome, for more than 3 months. No studies reported on pain relief of 30% or greater, or 50% or greater. Side effects were uncommon, and occurred only as mild reactions such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort (4 due to amitriptyline, 5 due to citalopram, 1 due to gabapentin, and 1 due to placebo). These 11 participants withdrew from the study due to these mild side effects. There were no serious side effects. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The available evidence in this review was of very low-quality due to a lack of data and small study sizes.
This review found that a single dose was effective in relieving migraine headache pain and associated symptoms of nausea, sensitivity to light, and sensitivity to sound. Pain was reduced from moderate or severe to no pain by two hours in about 3 in 10 people (32%) taking sumatriptan 100 mg, compared with about 1 in 10 (11%) taking placebo. Pain was reduced from moderate or severe to no worse than mild pain by two hours in 6 in 10 people (61%) taking sumatriptan 100 mg, compared with about 3 in 10 (32%) taking placebo. Almost a quarter (24%) of people taking sumatriptan 100 mg had freedom from pain at two hours which was sustained during 24 hours without the use of rescue medication, compared with fewer than 1 in 10 (8%) taking placebo. In addition to relieving headache pain, sumatriptan also relieved symptoms of nausea and sensitivity to light and sound by two hours in about half of those who took it, compared with about one-third of those taking placebo. Adverse events were mostly of short duration and mild or moderate in severity, and were experienced by about 4 in 10 (43%) of people taking sumatriptan 100 mg, and by 2 in 10 (23%) taking placebo. The 50 mg dose had slightly lower efficacy, but was associated with fewer adverse events. Treating attacks while pain was still mild was more effective than treating established attacks with moderate or severe pain intensity.
We included two studies in the review: one study of CNEP included 33 participants younger than one year old who had bronchiolitis and one study of CPAP included 37 participants who had dengue fever related illness. Both studies reported short-term improvements but no reports of clinically significant outcomes are available. With a small number of patients in both studies, the safety of either approach could not be evaluated. Both studies have methodological issues and were under-powered (had too few patients to detect a significant difference). No adverse events were reported in ether of the included trials. Well-designed, multicentre, controlled studies with adequate numbers of infants and which assess clinically important outcomes are needed, as we cannot comment on the safety of the intervention as it was not evaluated in the current studies. The major limitation of this review is that it has a very limited number of studies which include a very small sample of children.
Thirteen relevant trials with 1770 participants were analysed. All of them were of low quality. None of these trials analysed mortality, health related quality of life, economic outcomes or compliance with treatments. Some of these herbs may show benefits in improving symptoms, thyroid function and adverse effects. Unfortunately, we were unable to find reliable evidence to recommend a specific herbal preparation from 103 investigated formulations.
This review looks at original studies that reported the frequency or prevalence of risk behaviours, or information on HIV infection related to substitution treatment of opioid dependence to assess the extent to which oral substitution treatment prevents the transmission of HIV infection. It was not possible to accurately estimate the extent of reduction, but it is clear that oral substitution treatment reduces risk behaviours and also the probability of HIV infection amongst injecting drug users in substitution treatment.
The review authors searched the medical literature and identified five studies comparing these two methods. The studies included 211 patients with acute anterior shoulder dislocation; 113 patients underwent intra-articular lignocaine injection and 98 underwent intravenous analgesia with sedation. The review found that there may be no difference in the immediate success of manual reduction of the dislocated shoulder between patients receiving intra-articular lignocaine injection and those who received intravenous analgesia and sedation. However, intra-articular lignocaine injection may be associated with fewer side effects and a shorter stay in the emergency department before discharge from hospital. Compared with intravenous analgesia and sedation, intra-articular lignocaine may also be cheaper. However, the relatively small number of studies included in the review and the relatively small number of patients in each study means that the results of the review preclude definitive conclusions regarding the superiority of either method..
We identified seven studies, with a total of 542 adult patients who had head and neck cancer. However, many of the studies had shortcomings in their design or reporting. This has made it difficult to draw reliable conclusions. Overall, this review did not find any improvement in general quality of life or in levels of anxiety and depression following psychosocial intervention. In conclusion, there was limited good-quality evidence in this area, making it difficult to draw conclusions about the effectiveness of psychosocial interventions. Future good-quality research is required in this field and should target those in need of psychosocial intervention, in order to guide service development.
We planned to report evidence from clinical studies to evaluate the effectiveness and safety of different anti-inflammatory analgesic drugs compared with placebo, with each other or with no treatment. However, we were disappointed that we could not find any completed randomised controlled studies of these treatments or any evidence from non-randomised controlled studies. One study in cystic fibrosis-related arthropathy has finished and may provide some evidence when published. We suggest that there should be a randomised controlled study to look at the effects and the safety of using anti-inflammatory drugs or painkillers or both to manage the symptoms of cystic fibrosis-related arthritis. This is an update of a previously published review (date of last search 19 January 2016). Since no studies have been included in the review up until January 2016, we will still search for studies every two years, but will not publish an updated version of this review until we can include any new studies.
In July 2014, we found three studies (randomised controlled trials) of 246 children under the age of 16 years. All studies compared the two ways of giving medicine for pain relief after tonsillectomy (an operation to remove the tonsils). The studies were small, and generally of low quality. One study showed that the children in the 'around the clock' group took more medication, but they did not have better pain relief. There were no differences in pain relief or side effects between the two groups. There was not enough evidence to be sure which method is better for a child's pain relief after surgery. More high quality, large studies are needed.
The review included 11 trials. All were flawed which means that their results may be biased. Four trials involved people with acute fractures of the tibia (shin bone). Evidence from these trials showed that BMP may enhance healing of these fractures, and that people with these fractures when treated with BMP required fewer subsequent procedures. Six trials testing BMP for fractures that had not healed during first course of treatment (nonunions) showed BMP was neither better or worse at healing than bone grafts. One small trial found no difference between BMP and done grafts in people whose bone had been cut so in order to treat a healed but misaligned fracture. Trial participants who received BMP experienced similar adverse effects to those no receiving BMP (infection, hardware failure, heterotopic bone formation and immunogenic reactions). However, patients given BMP instead of bone autografts will have avoided problems associated with extraction of the bone from another site in their body. The review also included four economic evaluations. Three of these found that the costs associated with using BMP, based on one large trial of acute open tibia fractures, were likely to be higher than standard care treatment without BMP. The difference in costs decreased with increased fracture severity.
We included two randomised controlled trials with a total of 116 adult participants in this review. One compared large-volume (150 ml) hypertonic saline irrigation with usual treatment over a six-month period. The other compared 5 ml of nebulised saline twice a day with intranasal corticosteroids, treating participants for three months and evaluating them on completion of treatment and three months later. Both of these studies had important limitations in their methodology and we considered them to have a high risk of bias. Large-volume, hypertonic nasal saline versus usual care In the small trial of 76 participants our primary outcome of 'disease-specific health-related quality of life' was reported using a 0- to 100-point scale. At the end of three months of treatment, patients in the saline group were better than those in the placebo group and at six months of treatment there was a greater effect. We assessed the evidence to be of low quality for the three months follow-up and very low quality for the six months follow-up. Patient-reported disease severity was also evaluated but the trialists did not state the range of scores used, which made it impossible for us to determine the meaning of the data presented. No adverse effects data were collected in the control group but 23% of participants in the saline group experienced side effects including nosebleeds (epistaxis). General health-related quality of life was also measured in this study. No difference was found after three months of treatment but at six months there was a small difference (although the result is uncertain). We assessed the evidence to be of low quality. Low-volume, nebulised saline versus intranasal corticosteroids One small trial had 20 patients in each of the two arms being compared. Our primary outcome of disease-specific health-related quality of life was not reported. At the end of treatment (three months) there was an improvement in symptoms. The two studies were very different in terms of included populations, interventions and comparisons and so it is therefore difficult to draw conclusions for practice. The evidence suggests that there was no benefit of a low-volume (5 ml) nebulised saline spray over intranasal steroids, but there may be some benefit of daily, large-volume (150 ml) saline irrigation with a hypertonic solution compared with placebo, although the quality of the evidence was low for three months and very low for six months of treatment.
A total of 10,187 randomised participants from the 62 trials has been included. Maximum duration of intervention was 18 months. The reviewers suggest that supplementation appears to produce a small but consistent weight gain. There was no evidence in this updated review of a beneficial effect on mortality overall, but there may be a beneficial effect on mortality in people who are undernourished. Supplementation may also reduce the number of complications. The reported acceptance of supplements was variable between trials. Some adverse effects such as nausea or diarrhoea were reported. However, there were problems of study design and quality. More studies are required to confirm the beneficial effect on the number of complications, to establish whether there is a beneficial effect on mortality for undernourished elderly people and to provide evidence about whether protein and energy supplements can improve morbidity and functional status in frail older people.
We included 25 studies (with 8453 participants). There were six studies (2304 participants) comparing low-dose PPIs versus standard-dose PPIs (the dose used in clinical practice); 18 studies (6172 participants) comparing PPIs with placebo (pretend treatment); two studies (740 participants) comparing PPIs with H2RAs; five studies (1033 participants) comparing PPIs with prokinetics and two studies (407 participants) comparing PPIs plus prokinetics versus prokinetics alone. The duration of the treatment lasted at least two weeks. Seven studies reported treatment for two weeks, 12 studies reported treatment for four weeks and five studies reported more than six weeks of treatment. The treatment period was unclear in one study. Seventeen of the 25 studies were sponsored or funded by a pharmaceutical company and two by an institution grant. There was no information on funding in eight studies. Our review showed that PPIs are more effective than placebo, and are probably slightly more effective than prokinetics for the treatment of functional dyspepsia. Low-dose and standard-dose PPIs were similarly effective on the relief of indigestion, so we combined the results of the two doses of PPI. PPI was more effective than placebo, with 31% of the PPI group reporting no or minimal symptoms compared with 26% of the placebo group. The effect of PPI was probably slightly more effective than H2RAs; however, the two studies involved in the analysis were so different that it may have influenced the results. There was no difference in the number of reported side effects when comparing PPIs, H2RAs and prokinetics. The studies evaluating the effect of PPIs compared to placebo or PPIs combined with prokinetics versus prokinetics were in general of good quality. However, the studies that compared PPIs versus H2RAs and prokinetics had serious quality issues.
Conclusions: There are no randomized clinical trials on this topic; some institutional, non-clinical trials studies have suggested improved overall survival and seizure control with higher extent of resection. However, physicians should approach each case individually and weigh the risks and benefits of biopsy versus surgical resection, as well as incorporate patient preference into their clinical decision-making. Prognostic factors such as patient age, tumor size, and tumor location as well as potential implications for quality of life should be taken into account.
The objective of this review was to assess the efficacy of this treatment. As a result of the small number of studies that we were able to include in this review and the limitations of those studies, we were unable to draw any conclusions regarding the effectiveness of meditation therapy for ADHD. No adverse effects of meditation in children have been reported. More trials are needed on meditation therapies for ADHD so that conclusions can be drawn regarding its effectiveness.
We found 11 studies (current until July 2015) that described 695 computed tomography pulmonary angiography results, 665 lung scintigraphy results and no magnetic resonance angiography results. Studies on lung scintigraphy used varying techniques. Overall, these studies were of poor quality; therefore, we could not analyse results together to obtain a single estimate of their accuracy. The identified studies followed-up patients clinically to confirm the absence of pulmonary embolism as revealed on the initial scan, so information could be used to draw conclusions only on the ability of these imaging tests to exclude pulmonary embolism, not on their ability to establish the diagnosis. Both computed tomography pulmonary angiography and lung scintigraphy appear appropriate for excluding pulmonary embolism in pregnancy. Almost no cases were missed, especially when the imaging test indicated the absence of disease without a doubt. However, this result should be interpreted with care because of the low quality of and variation between identified studies. Around 5% of the scans were unclear, but this percentage was as high as 36% in one study. About 3% of all women included in the studies had pulmonary embolism. We do not know which of the tests is better because tests were not directly compared in the same patients, and because aspects besides test accuracy need to be taken into account. Major limitations of this review include the use of clinical follow-up within studies to confirm the absence of disease, unclear test results and the inability of studies to provide information on the accuracy of these tests in establishing rather than rejecting the diagnosis. High-quality research is needed to investigate the use of computed tomography pulmonary angiography, lung scintigraphy and magnetic pulmonary angiography in the same patient groups.
Authors from Cochrane Oral Health reviewed existing studies to find all available evidence up to November 2014. We searched scientific databases for clinical trials testing the effects of fluoridated milk compared with non-fluoridated milk. Treatment had to be used and monitored for a minimum of two years. We found one unpublished study that included 180 three-year olds who were given either fluoridated or non-fluoridated milk at nursery schools in an area with high prevalence of dental cavities and a low level of fluoride in drinking water. After three years, 92% of the children were available for analysis. The evidence suggests fluoridated milk may be beneficial to schoolchildren, substantially reducing the formation of cavities in baby teeth. There was no information available about any possible adverse events. The evidence was considered to be low quality due to the lack of relevant studies, the risk of bias in the identified study and concerns over the applicability of the results to different settings and populations. Additional studies of high quality are needed before we can draw definitive conclusions about the benefits of milk fluoridation.
We searched the literature in January 2018. We found two studies, enrolling 157 participants in total, that tested the effect of systemic corticosteroids on breathlessness in adults with cancer, compared to a dummy medicine (placebo). One study lasted seven days, and the other study lasted 15 days. Both studies compared a corticosteroid (oral (by mouth) dexamethasone) to a dummy medicine with no properties to reduce breathlessness, which we included in our analyses. We were interested in the primary outcomes of participant-reported breathlessness intensity, quality and burden. We were also interested in the secondary outcomes of serious side effects, participant satisfaction with treatment and participant withdrawal from trial. We could not complete many of our planned analyses due to the small number of studies, the different medicines and comparisons, and outcomes that the studies reported. We did conduct one analysis of 114 participants to assess change in breathlessness intensity/relief from baseline. We found that corticosteroids had no beneficial effect compared to a dummy medicine on reducing breathlessness intensity in people with cancer. We found that the frequency of side effects was similar between groups, and corticosteroids were generally well tolerated. None of the studies measured participant satisfaction with treatment. Participant withdrawals were 15% and 36% in the two studies. The current evidence was based on only two studies with a small number of participants. We rated the quality of the evidence from these studies using four levels: very low, low, moderate or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. We judged the quality of the evidence in this review to be very low, downgraded due to problems with study quality and too few data. We are very uncertain of the results. More high-quality studies are needed to determine if corticosteroids are effective for dyspnoea in people with cancer.
This review shows that intravenous infusions of infliximab, a TNF-α blocking agent is effective in inducing clinical remission, promoting mucosal healing, and reducing the need for colectomy in patients with active ulcerative colitis whose disease has not responded to conventional treatment.
The researchers identified six studies that included a total of 2324 participants. Two studies compared briakinumab to placebo (a fake medicine) and four studies compared ustekinumab to placebo. All of the studies were high quality. There was no difference in the proportion of briakinumab and placebo participants who achieved remission. An increase in side effects or severe side effects were not seen with briakinumab compared to placebo. The most common side effects in briakinumab participants were reactions at the site of injection and infections. Based on the results of these two studies the manufacturers of briakinumab stopped production of this medication. High quality evidence suggests that ustekinumab is better than placebo for helping participants achieve remission and for reducing symptoms of active Crohn's disease. Different doses of ustekinumab were investigated and moderate to high quality suggests that 6.0 mg/kg is the most effective dose. An increase in side effects or serious side effects was not seen with ustekinumab compared to placebo. Infections were the most common adverse event in ustekinumab patients. Worsening of Crohn's disease and serious infections were the most common serious side effects in the ustekinumab studies. Ustekinumab is a promising as a therapy for inducing remission and improving symptoms in people with Crohn's disease. Further studies are required to determine the long-term effectiveness and safety of ustekinumab in patients with moderate to severe Crohn's disease. The ideal dose of ustekinumab also needs to be determined.
We included two well-designed studies with a total of 130 adult participants, each study using a different species of gastrointestinal helminth (human hookworm in one study and pig whipworm in the other) as the intervention. Both studies found no significant efficacy from helminths, although one helminth species (Trichuris suis, the pig whipworm) reduced the need for participants to take tablets as ‘rescue medication’ during the grass pollen season. Adverse events such as abdominal pain and flatulence were commoner in the helminth group, but the two helminths species studied did not cause serious adverse reactions. Currently there is insufficient evidence to support the use of helminths for allergic rhinitis in routine clinical practice. More preclinical studies are needed, before larger and extended duration clinical trials of helminths for allergic rhinitis are performed.
We searched for studies on 2 November 2015 and included four small randomised controlled trials involving a total of 567 women who were less than 11 weeks' to 24 weeks' pregnant at the start of the trials. The quality of the evidence was assessed as low or very low and the overall risk of bias was unclear. Myo-inositol was associated with a reduction in the rate of gestational diabetes (low quality evidence), reducing the incidence from 28% in women who did not take the supplement, to between 8% and 18% in the women who took it. There was no difference between groups in terms of the number of women who had hypertensive disorders of pregnancy (including pre-eclampsia, eclampsia and abnormally high blood pressure during pregnancy) (very low quality evidence). The trials did not provide any information about the number of babies that died (either before being born or shortly afterwards) or babies that were large-for-gestational age. There were no maternal adverse effects of therapy in the two trials that reported on this outcome (the other two trials did not mention this). This review did not find any impact on other outcomes such as the risk of having a caesarean section (low quality evidence), a large baby, obstructed labour when the baby's shoulder becomes stuck (shoulder dystocia) or a baby with low blood glucose levels. This may be due to the trials being too small to detect differences in these outcomes and the outcomes not being reported by all trials. All four trials were from Italy. The included trials did not report on a large number of other mother and baby outcomes listed in this review and nor were there any data relating to longer-term outcomes for the mother or the infant, or the cost of health services. Myo-inositol as a dietary supplement during pregnancy shows promise in preventing gestational diabetes but there is not enough evidence at this stage to support its routine use. Further large, well-designed, randomised controlled trials are required to assess the effectiveness of myo-inositol in preventing gestational diabetes and improving other health outcomes for mothers and their babies. Ideally, future studies should consider involving women from different ethnicities and with differing risk factors for gestational diabetes. It would be useful for future studies to consider the ways that myo-inositol can be used (different doses, frequency and when to take it) and compare the intervention with a placebo control, diet and exercise or pharmacological interventions. We recommend that future studies utilise the outcomes listed in this review and that potential harms, including adverse effects are included.
In this overview of Cochrane Reviews we examined all the evidence on how well morphine-like drugs worked, mostly when taken by mouth or through a skin patch, how many people had side effects, and how severe or troublesome those side effects were — for example, whether they caused participants to stop taking their medicines. In May 2017, we found nine reviews with 152 included studies and 13,524 participants. The studies were often small, and compared many different preparations. They used different study designs and different ways of showing their pain results. Outcomes of importance to people with cancer pain were often not reported. For two drugs (morphine by mouth and fentanyl patches) more than 19 in 20 people had pain that went from moderate or severe before taking morphine-like drugs, to pain that was no worse than mild within 14 days if they can tolerate the side effects. Most people taking a morphine-like drug had at least one side effect. Only about 1 person in 10 to 2 people in 10 stopped taking it because of side effects. The most common side effects were constipation, and nausea and vomiting. At one level these are encouraging results, and generally agree with surveys of how well the WHO advice works in cancer pain. On another level, the quality of studies in the reviews was generally poor. We would like better study design, and especially better study reporting, which should include the outcome of pain reduced to a level where people with cancer can cope with it (no pain or mild pain). We found that the Cochrane Reviews were of high quality. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. We rated the evidence in the reviews as very low quality.
We found three small trials (in total 223 pregnant women with type 1 diabetes) looking at different blood glucose targets: very tight, tight, moderate, and loose. The quality of the studies and therefore the strength of the evidence was very low or low, so future research may change the results. There were very few differences between very tight and tight-moderate blood glucose targets in two trials, although there were more cases of low blood glucose (hypoglycaemia) and longer hospital stays for women who had very tight blood glucose control. A single trial compared tight, moderate, and loose blood glucose targets. In the loose target group, more women had pre-eclampsia, and there were more caesareans and large babies. There were few differences between the tight and moderate groups, although more women in the tight control group had low blood glucose in the first half of pregnancy. The evidence does not show much difference between moderate, tight and very tight blood glucose targets, although a loose blood glucose target may be worse for mothers and babies. However, the studies were small and the evidence is weak, so we do not yet know the best blood glucose target for women who have diabetes before becoming pregnant.
We included three randomised clinical trials. In these trials, people with metastatic and incurable colorectal cancer, without symptoms, received chemotherapy straight away (standard group) or their chemotherapy was delayed (intervention group). There were a total of 176 participants In the standard groups and 175 in the intervention groups. The available data allowed us to complete analyses for overall survival and toxicities. Participants with metastatic, incurable colorectal cancer without symptoms, who received chemotherapy straight away, did not live longer than those whose chemotherapy was delayed until symptoms appeared. For toxicities measures, our findings were inconclusive due to sparse data from only two trials and few participants. There were insufficient data to compare other outcomes of interest, such as quality of life, progression-free survival (the length of time during and after treatment that a person lives with the disease, but it does not get worse), and compliance with chemotherapy (whether a participant was able to complete the chemotherapy regimen). Based on very sparse data and uncertainty of the evidence, we were unable to establish whether there was a difference in overall survival and other important outcomes in people with metastatic, incurable, colorectal cancer, who received chemotherapy either straight away or waited until after symptoms had appeared.
The number and size of the trials investigating adjunctive corticosteroids for HIV-infected patients co-infected with PCP is small (the six trials included in the meta-analysis comprised 242 individuals in the intervention groups and 247 individuals in the control groups; the trial on infants comprised 47 individuals in the intervention group and 53 in the control group). Follow-up ranged from three to 14 months. The evidence from this review was of high quality for mortality and of moderate quality for need for mechanical ventilation and suggests a beneficial effect for adult patients with substantial hypoxaemia. For infants (18 months or younger) with HIV and suspected PCP there is insufficient evidence on whether the effect of adjunctive corticosteroids could improve survival (the confidence interval for the estimate of effect is wide, includes both clinically relevant benefit and harm and is of moderate quality).
The review included three studies with 77 people with cystic fibrosis aged between 18 and 64 years of age. The studies looked at the impact of the timing of hypertonic saline inhalation in relation to airway clearance techniques. The studies reported immediate outcomes after inhalation of hypertonic saline before, during or after physical airway clearance techniques. All studies were short, involving only one to three treatments of each timing regimen. While outcomes such as lung function did not show any difference between the regimens, people with cystic fibrosis perceived that inhaling hypertonic saline before or during airway clearance techniques may be more effective and satisfying than inhaling hypertonic saline after airway clearance. No studies comparing morning and evening inhalation were found. The long-term efficacy of hypertonic saline has only been established for twice-daily inhalations; however, if only one dose per day is tolerated, the time of day at which it is inhaled could be based on convenience or tolerability until further evidence is available. Overall, the quality of the evidence was low. The only issues perhaps affecting the quality related to the fact that it was not possible for participants to be blinded to the treatment they received. However, because the studies were short-term and most of the significant results were based on perceived efficacy, timing of administration of hypertonic saline needs further study.
This review identified seven trials on the treatment of jellyfish stings primarily involving two jellyfish species—Physalia (Bluebottle) and Carybdea alata (Hawaiian box) jellyfish—as well as two trials that are in progress. Many different types of treatments were tested in these trials. Large variation was observed between the duration of treatment among trials. Evidence of limited quality from a single study suggested that hot water immersion relieved pain. This evidence may not apply to other species of jellyfish because of large variability in the effects of stings. Further research should be conducted to help practitioners better understand the most effective treatments for jellyfish stings.
We included 51 studies (2793 participants) in the review and analysed results from 45 studies (2491 participants). There are 11 ongoing studies and three awaiting classification. Funding sources included governments, charities, institutions, industry (in part, n = 1); over half were unspecified (n = 29). Compared to systemic analgesia, we found that peripheral nerve blocks reduce pain, reduce the risk of becoming confused (e.g. not knowing the date, time, or location) (for every 12 people treated one fewer will become confused), reduce itching (for every 4 people treated one fewer will develop itch), hospital length of stay (equivalent to 0.75 day) and increase patient satisfaction for pain treatment (equivalent to 2.4 points more on a 0 to 10 scale). We did not find a difference in time to first walk after surgery. Two people had complications: one local haematoma and one delayed persistent muscle weakness. The quality of evidence for peripheral nerve blocks compared with systemic pain relievers was rated as moderate to very low. The quality of evidence for peripheral nerve blocks compared to neuraxial blocks was rated as high for patient satisfaction, moderate for reducing itch, similar pain relief, low for similar block-related complications, hospital length of stay and time to first walk. Evidence for confusion was assessed as very low quality. Evidence quality was downgraded to low or very low due to flawed study designs and limited numbers of trials and participants.
We searched for studies in the medical literature until August 2013. The review includes 10 randomised or quasi-randomised controlled trials that recruited 527 children. Four trials compared different surgical versus non-surgical treatments; three compared different methods of non-surgical treatment and three compared different methods of surgical treatment. Generally we are unsure about the results of these trials because some were at risk of bias, some results were contradictory and usually there was too little evidence to rule out chance findings. Most trials failed to report on self-assessed function or when children resumed their usual activities. Comparing surgical versus non-surgical treatment Low quality evidence (one trial, 101 children) showed children had similar function at two years after having surgery, involving external fixation, compared with those treated with a plaster cast. The other three trials did not report this outcome. There was moderate quality evidence (four trials, 264 children, aged 4 to 12 years, followed up for 3 to 24 months) that surgery reduced the risk of malunion (the leg is deformed) compared with non-surgical treatment. However, low quality evidence (four trials) indicated that there were more serious adverse events such as infections after surgery. There was low quality evidence (one trial, 101 children) of similar satisfaction levels in children and parents with surgery involving external fixation and plaster cast only. However, there was low quality evidence (one trial, 46 children) that more parents were satisfied with surgery involving an internal nail than with traction followed by a cast and that surgery reduced the time taken off from school. Comparing various non-surgical treatments Very low quality evidence means that we are very unsure if the rates of malunion differ or not between children treated with immediate plaster casts versus with traction followed by plaster cast (one trial, 42 children), or between children treated with traction followed by either a functional orthosis (a brace or cast that allows some movement) or a cast (one trial, 43 children). We are very unsure if either function or serious adverse events differ between young children (aged two to seven years) immobilised in single-leg versus double-leg casts (one trial, 52 children). However, single-leg casts appear to be easier to manage by parents and more comfortable for the child. Comparing various surgical treatments Very low quality evidence means that we are very unsure if the rates of malunion, serious adverse events, time to return to school or parental satisfaction actually differ in children whose fractures were fixed using internal nails or external fixation (one trial, 19 children). The same applies to the rates of serious adverse events and time to resume full weight-bearing in children treated with dynamic (less rigid) versus static external fixation (one trial, 52 children). Very low quality evidence (one trial, 47 children) means that we do not know if malunion, serious adverse events and time to resume weight-bearing actually differ between intramedullary nailing versus submuscular plating. However, there could be more difficulties in plate removal subsequently. Conclusions This review found insufficient evidence to determine if long-term function differs between surgical and conservative treatment of thigh bone fractures in children aged 4 to 12 years. It found surgery resulted in lower rates of malunion but increased the risk of serious adverse events, such as infections. It found internal nailing may speed up recovery. The review found there was insufficient evidence from comparisons of different methods of non-surgical treatment to clearly show that any type of non-surgical treatment is better than any other. The same conclusion applies to comparisons of different methods of surgical treatment.
This Cochrane review included 17 randomised controlled trials which compared treatment with the androgens DHEA or T with placebo or no treatment in a total of 1496 women, almost all of whom had been identified as 'poor responders' to standard assisted reproduction protocols. The main outcomes were live birth (defined as delivery of a live baby after 20 weeks gestation) or ongoing pregnancy rates, miscarriage, clinical pregnancy rates (fetal heartbeat confirmed on ultrasound) and multiple pregnancy rates. We examined the evidence published up to 12 March 2015. DHEA and T use may be associated with increased live birth rates. The evidence for the use of DHEA suggested that in women with a 12% chance of live birth with placebo or no treatment, the live birth rate in women using DHEA will be between 15% and 26%. The evidence for the use of T suggested that in women with an 8% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 10% and 32%. When we removed from the analyses the studies at high risk of bias, this increase was no longer present for DHEA or T. There is insufficient evidence to draw any conclusions about the safety of either androgen. The quality of the trials was moderate, and the main limitations were lack of blinding, inadequate reporting of study methods and small sample sizes in some included trials.
This review found dietary advice or counselling and blood glucose level monitoring for women with borderline GDM helped reduce the number of macrosomic and LGA babies. A single trial found that the interventions led to more inductions of labour. The interventions did not increase the risk of caesarean sections, operative vaginal births or women's weight gain in pregnancy. These findings were based on four small randomised controlled trials (involving 543 women). The trials were of moderate to high risk of bias and only data from 521 women and their babies is included in our analyses. Until additional evidence from large well designed randomised trials becomes available, current evidence is insufficient to make conclusive recommendations for the management of women with pregnancy high blood glucose concentrations not meeting GDM (or type 2 diabetes) diagnostic criteria.
We found nine studies up to January 2017, involving 994 participants, that looked at the benefits of occupational therapy interventions for adults with stroke who had problems with activities of daily living. This is an update of the Cochrane review first published in 2006. We found that occupational therapy for people with stroke can improve their ability to carry out these daily activities and stop them deteriorating in those abilities. We found no evidence that occupational therapy reduced rates of death or the need to be cared for in an institution, or affected mood or distress of the participant. We did not collect data on carer-related outcomes or participant satisfaction with the service. There were few studies measuring our outcomes of interest and we judged the quality of the evidence to be of low-quality. Many of the studies did not report methods sufficiently clearly and it was not possible to mask the occupational therapy from the person giving or receiving the treatment; this could also have influenced the results in our studies. We did not have sufficient good-quality evidence to be certain of our results and we cannot be certain that future studies will not change these conclusions.
We searched and reviewed all randomised controlled trials that had been undertaken to evaluate the benefit of CPAP in adult patients with sleep apnoea. Some of the trials had methodological flaws, although more recent studies have begun to use appropriate forms of control. The overall results demonstrate that in people with moderate to severe sleep apnoea CPAP can improve measures of sleepiness, quality of life and associated daytime sleepiness. CPAP leads to lower blood pressure compared with control, although the degree to which this is achieved may depend upon whether people start treatment with raised blood pressures. Oral appliances are also used to treat sleep apnoea but, whilst some people find them more convenient to use than CPAP, they do not appear to be as effective at keeping the airway open at night. Further good quality trials are needed to define who benefits, by how much and at what cost. Further trials are also needed to evaluate the effectiveness of CPAP in comparison to other interventions, particularly those targeted at obesity.
We found five randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with a total of 201 participants. Most trials did not report on type of diabetes. Younger diabetic participants and children were underrepresented in our included trials (one trial only). Participants in four trials received treatment with insulin lispro, and one trial with 45 participants investigated insulin aspart. The average follow-up as measured by mean hospital stay ranged between two and seven days. The study authors termed the diabetic ketoacidosis being treated with insulin analogues or regular insulin as mild or moderate. This evidence is up to date as of October 2015. Our results are most relevant for adults with mild or moderate diabetic ketoacidosis due to undertreatment of diabetes. No deaths occurred. Time to resolution of diabetic ketoacidosis from the start of therapy did not differ substantially between the two insulin treatment schemes (approximately 11 hours). Hypoglycaemic (low blood sugar) episodes were comparable: 118 per 1000 participants for intravenous insulin compared with 70 per 1000 participants for subcutaneous insulin lispro (no statistically significant difference). The mean length of hospital stay also showed no marked differences. No trial reported on side effects other than hypoglycaemic episodes or investigated patient satisfaction. No serious events associated with diabetic ketoacidosis were seen during insulin lispro treatment. Our results were limited by mostly low- to very low-quality evidence, mainly because the number of included trials and participants was low. Further research is very likely to have an important impact on our findings.
This review included data from 11 clinical trials involving 404 participants. The studies had very small numbers of participants, so can provide only limited information. Ten different active treatments were studied, including prednisolone, pulsed oral dexamethasone, azathioprine, cyclophosphamide, cyclosporine, dapsone, mycophenolate, plasma exchange, topical epidermal growth factor and traditional Chinese medicine. This review found insufficient information to conclude which is the most effective and safest treatment plan. We found that mycophenolate mofetil appears to be more effective than azathioprine in controlling disease, although no difference was seen in remission. We found that taking azathioprine and cyclophosphamide decreased the amount of glucocorticoids required. Topical epidermal growth factor decreased time required for lesions to heal by 6 days (median). We found no difference in withdrawal due to adverse events in any study, although differing adverse event profiles were observed for each intervention. We were not able to conclude which treatments are superior overall. Multiple treatments are available for pemphigus vulgaris and pemphigus foliaceus and there is a variation in dosage plan and combination of drugs used, which makes choice of treatment schedule complex. In addition, response to treatment can vary between individuals. Treatments need to be chosen after careful consideration of the potential benefits and side effects, in the context of the individual's other medical conditions. This review found insufficient information to conclude which is the most effective and safest treatment regimen. Further studies are required to determine the optimal treatment regimen, especially to assess the optimal glucocorticoid dose, the role of adjuvant immunosuppressive medications, and long-term adverse events to improve harm:benefit analyses.
Using more chemotherapy drugs in combination seems to help women with advanced or recurrent endometrial cancer to live for longer and to delay the cancer from spreading or getting worse. However, giving these extra drugs may cause more serious short-term side effects. We do not know what effect using more drugs has on long-term side effects, control of symptoms or quality of life because they were poorly studied in the individual trials included in this review.
This review found that progressive muscle relaxation with or without imagery and relaxation may help with spasmodic (acute, cramping pain) symptoms of period pain. Also that pain management training and relaxation plus biofeedback may help with period pain in general. The results are not conclusive due to the small number of women in the trials and the poor methods used in some of the trials.
We searched electronic databases in June 2014, adding to the research done in a previous version of this review. The same five trials were included in our analysis, comprising 924 epileptic children (all below 16 years old) who were randomly assigned to either early removal of AEDs (before completing two years without seizures); or late withdrawal of AEDs (after completing two years without seizures). Considering all evidence, we found that stopping AED intake before completing two years without seizures increases the risk of seizure relapse by around 34%. This percentage is increased if the child has partial seizures (if the electrical burst only involves a part of the brain, resulting mainly in localized symptoms); or an abnormal electroencephalogram (EEG) record (unusual patterns of electrical activity in the brain). Other factors that might be related to a higher relapse rate are: age below two years or above 10 years when epilepsy started; history of status epilepticus (convulsions longer than 30 minutes); an IQ lower than 70; and high frequency of seizures before and during treatment. Overall, the included trials provided a moderate quality of evidence. The review of trials found that there is evidence to support waiting at least two years or more seizure free before discontinuing AEDs in children, especially if they had partial seizures or abnormal EEG. There is not enough evidence to show the best time to withdraw antiepileptic drugs in adults with epilepsy who are free of seizures. There is not enough evidence that demonstrates the optimal time to remove antiepileptic drugs in people (children or adults) with generalised seizures (if the electrical discharges affect the whole brain, causing global symptoms). More research is needed, particularly involving adults and those with generalised seizure types.
The search yielded two studies dealing with the preventive aspect of the condition. The first trial found weekly fluconazole significantly effective in preventing clinical episodes from occurring as compared to placebo. However,this regimen lead to emergence of species resistant to azoles. The second trial with three arms of comparison; Clotrimazole, Lactobacillus and placebo gave no definitive results in preventing an episode of VVC. Neither of the included studies investigated the effects of HAART(Highly Active Antiretroviral Therapy) or any other form of antiretroviral treatment on VVC nor did they explore difference in quality of life, viral shedding in vaginal secretions (infectivity) ,patient preference for route of administration or the cost.
We found 15 randomised controlled trials (a type of experiment in which people are randomly allocated to one or more treatment groups) that compared the use of vasodilators versus placebo or no treatment in a total of 1326 women undergoing fertility treatment. The evidence is current to October 2017. Only three of the included studies reported live birth rates. Overall, vasodilators probably make little or no difference in rates of live birth. Moderate-quality evidence shows that vasodilators probably increase overall rates of side effects (including headache and tachycardia (faster than normal heartbeat)) in comparison with placebo or no treatment. However, low-quality evidence suggests that vasodilators may increase the chance of becoming pregnant. The evidence is of low to moderate quality. More research is needed (one study is ongoing and will be incorporated into this review in a subsequent update).
One trial with longer follow up (more than 10 years) showed improved survival with adjuvant radiotherapy but this improvement did not exist at 5 years follow up. Radiotherapy reduced the number of men whose cancer spread to other parts of the body (metastases). We found that radiotherapy improved local control in the prostate bed and did reduce the risk of cancer recurring. Radiotherapy reduced the number of men with an abnormal PSA blood test, but the importance of this is uncertain. Radiotherapy does increase the risk of side effects, (mostly mild) affecting bladder and bowel function. It is not clear from these studies whether it is better to give radiotherapy immediately after surgery when these high risk features are present, or whether it would be just as good watching for a time, and only giving radiotherapy once the PSA blood test starts to rise. This is the subject of ongoing studies. Radiotherapy after radical prostatectomy should be considered if high risk features are present, but the optimal timing is unclear.
We found 43 studies involving 6617 people who had CKD that examined if eHealth interventions improve patient care and health outcomes. eHealth interventions used different modes of technology, such as Telehealth, electronic monitors, mobile or tablet applications, text message or emails, websites, and DVDs or videos. Interventions were classified by their intention: educational, reminder systems, self-monitoring, behavioural counselling, clinical decision-aids and mixed interventions. We categorised outcomes into nine domains: dietary intake, quality of life, blood pressure control, medication adherence, results of blood tests, cost-analysis, behaviour, physical activity and clinical end-points such as death. We found that it was uncertain whether using an eHealth interventions improved clinical and patient-centred outcomes compared with usual care. The quality of the included studies was low, meaning we could not be sure that future studies would find similar results. We are uncertain whether using eHealth interventions improves outcomes for people with CKD. We need large and good quality research studies to help understand the impact of eHealth on the health of people with CKD.
The evidence is current to December 2012. We identified a total of 11 controlled studies, including a total of 742 children, where clonidine was compared to another medication or to a dummy treatment (placebo). We found evidence that when clonidine is given at an adequate dose (4 µg/kg) it is effective in reducing the need for pain relief after surgery for children (and probably reduces the children's pain) when compared to a placebo. The evidence is less clear when clonidine is compared to the sedative drug midazolam; this is likely to relate to differences in the design of the clinical trials. The side effects of clonidine did not seem to be a significant problem at the doses used, although in some of the studies the investigators took measures to prevent such side effects by the use of other medications. Overall, the evidence so far is of low or unclear quality. Further research is required to confirm under what conditions clonidine premedication is most effective in children.
Our searches are current to May 2015. We found no new trials. In previous searches, we found seven randomised controlled trials that used beta2-agonist drugs for people with acute bronchitis. Two trials studied children aged one to 10 years (134 participants) and five were conducted in adults (418 participants). None of the studies reported receiving grants from drug-making companies to conduct the study, but people who work for a drug maker were listed as authors on reports from two trials and study drugs were supplied free of charge by the company in three trials. Daily cough scores were no different between children given oral beta2-agonists and children in the placebo control groups. Daily cough scores, or the number of people still coughing after seven days, did not change in the adult trials either. However, the results were mixed. Some trials show a benefit and some show no benefit. This may be because some participants also had wheezing or other signs of narrowed airways, in which case beta2-agonists may be helpful only for them. More of the adults taking beta2-agonists had tremor, shakiness or nervousness. We rated this as low or moderate. There were few trials, with small numbers of people with acute bronchitis or cough. The trials were of short duration (three to seven days) and only two used inhaled beta2-agonists, which is now the usual way the drug is taken by adults and older children. Some important information about how the trial was done was not mentioned in the papers giving results for many of the trials.
This review included seven studies, with a total of 662 adolescents of both genders. AIS from 15° to more than 45° curves were considered. Elastic, rigid (polyethylene), and very rigid (polycarbonate) braces were studied. The evidence is current to October 2013. Funding sources were not reported or external governmental or scientific agencies. We did not find any results on pulmonary disorders and disability. Quality of life was not affected during brace treatment (very low quality evidence); quality of life, back pain, and psychological and cosmetic issues did not change in the long term (very low quality evidence). Rigid bracing seems effective in 20° to 40° curves (low quality evidence), elastic bracing in 15° to 30° curves (low quality evidence), and very rigid bracing in high degree curves above 45° (very low quality evidence); rigid was more successful than an elastic bracing (low quality evidence), and a pad pressure control system did not increase results (very low quality evidence). No specific harms were reported. Primary outcomes such as pulmonary disorders, disability, back pain, psychological and cosmetic issues, and quality of life should be better evaluated in the future. Side effects, as well as the usefulness of exercises and other adjunctive treatments to bracing should be studied too. The evidence was moderate to very low quality. Reason for downgrading were evidence coming from few randomized trials with few participants and many lost at follow-up or from observational prospective controlled studies. An issue in the field of AIS is the high rate of failure of RCTs, since parents want to choose with physicians the preferred treatment for their children. Thus, it is challenging to obtain high quality evidence in this field.
We included eight studies where the participants were randomly assigned to two groups: one group received the extra food and the other group was a control, either receiving no food or food with very low nutritional content. Although the impact of supplementary feeding on child growth appeared to be negligible, it is not possible to draw any conclusions until we have studies that involve larger numbers and do not allow assessors to know who is receiving the intervention. Although it is difficult to determine whether community-based supplementary feeding helps to promote the growth of children from birth to five years in low- and middle-income countries, it is obviously vital to continue to provide food, health care and sanitation to those who need them.
Editorial peer review is used world-wide as a tool to assess and improve the quality of submissions to paper and electronic biomedical journals. As the information revolution gathers pace, an empirically proven method of quality assurance is of paramount importance. The increasing availability of empirical research on the possible effects of peer review led us to carry out a review of current evidence on the efficacy of editorial peer review. We found few studies of reasonable quality, and most of these were concerned with the effects of blinding reviewers and/or authors to each others' identity. We could not identify any methodologically convincing studies assessing the core effects of peer review. Major research is urgently needed.
A systematic review of the literature and a quantitative assessment found that VCT is an effective strategy for reducing some HIV-related risk behaviors, including decreasing the number of sexual partners of participants. Condom use was also significantly increased among participants who tested HIV-positive during VCT. Future research is needed to understand how VCT can be delivered more effectively to maximize its potential as an HIV prevention strategy.
However, this review of nine randomised controlled trial found that home care resulted in an improvement in people's quality of life, but has an unpredictable effect on the risk of being admitted to hospital. We could only find information on the cost of care from one study, but this indicated that home care was an expensive form of care. More research is needed to confirm the usefulness of home visits for people with COPD.
However, there is no direct evidence that has proven that these outcomes are valid because there have been no long-term trials that have shown that an improvement in these tests translates into reduced mortality or morbidity. Patients who fail to have sustained viral responses after an initial course of therapy do become potential candidates for retreatment; some of them may be intolerant to ribavirin, and possibly even the newer protease inhibitors, so retreatment would have to be with interferon alone. It has also been speculated that long-term treatment (namely treatment for several years) might be beneficial; such long-term therapy would be further complicated if multiple drugs were used because of the additional drug toxicities and costs, so interferon alone could be considered. This review addressed the ability of interferon monotherapy to favorably alter the clinical course of chronic hepatitis C when it is used to retreat patients who failed at least one previous course of therapy. Seven trials were identified, including two large ones (a total of 1676 patients), known as "HALT-C" and "EPIC3", that specifically were designed to use low-dose pegylated interferon for three to five years in patients with evidence on liver biopsy of severe fibrosis and who had failed to have a sustained viral response to a course of standard combination (pegylated interferon plus ribavirin) therapy in the past. Both trials were at low risk of bias. A third trial designed to address the use of pegylated interferon monotherapy for 48 weeks in improving survival in patients with cirrhosis (Childs A or B) was terminated early because of the results of the HALT-C and EPIC3 trials, so three trials have provided mortality and hepatic morbidity data. When all three trials were considered, there was no significant effect of the treatment on either all-cause mortality (78/843 (9.3%) versus 62/867 (7.2%); risk ratio (RR) 1.30, 95% confidence interval (CI) 0.95 to 1.79; 3 trials) or hepatic mortality (41/532 (7.7%) versus 40/552 (7.2%); RR 1.07, 95% CI 0.70 to 1.63; 2 trials); however, all-cause mortality was higher in the recipients of the pegylated interferon (78/828 (9.4%) versus 5 7/848 (6.7%); RR 1.41, 95% CI 1.02 to 1.96) when only the two low risk of bias trials were considered. The excess deaths appeared to be from non-liver causes. Variceal bleeding occurred less often in the treated patients (4/843 (0.5%) versus 18/867 (2.1%); RR 0.24, 95% CI 0.09 to 0.67), but there were no differences seen with regard to the subsequent development of other manifestations of end-stage liver disease (that is, encephalopathy, ascites, hepatocellular carcinoma, liver transplantation). One trial reported quality of life data; the treated patients had increases in their pain scores. No cost data were available. The recipients of the pegylated interferon generally had more adverse events; statistically significant differences were seen for the occurrence of hematologic complications, infections, flu-like symptoms, and rashes. Those receiving interferon were more likely to have sustained viral responses (20/557 (3.6%) versus 1/579 (0.2%); RR 15.38, 95% CI 2.93 to 80.71) and were also more likely to have improvements in markers of inflammation. No difference was demonstrated regarding the effect of the treatment on markers of fibrosis. The use of longer-term (several years) interferon monotherapy in patients with severe underlying hepatic fibrosis who have failed previous courses of treatment is not supported by the evidence; no trials providing data regarding clinical outcomes were identified in other potential treatment scenarios. Two of the commonly employed surrogate markers, sustained viral response and markers of inflammation, failed to be validated since they improved even though the clinical outcomes did not (or may even have become worse). This failure to validate the sustained viral response in this group of patients with a low sustained viral response rate suggests that the presumed validity of the use of sustained viral responses in other groups of patients with chronic hepatitis C viral infections who receive treatment must be formally validated.
We searched for both published and unpublished studies comparing oropharyngeal colostrum versus a control such as water, placebo, or no oral priming. We included only clinical trials reporting outcomes in preterm babies (< 37 weeks' gestation). The evidence is up-to-date as of August 2017. We did not limit the review to any particular region or language. Six studies were eligible for inclusion, involving 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Reviewers noted no differences between OPC and control for rate of NEC, infection, or death before hospital discharge. Similarly, they observed no difference in length of hospital stay between OPC and control babies. Infants who received OPC achieved full milk feeds on average 2.5 days earlier than those given placebo or no intervention. However, included studies were small, data were insufficient, and study designs were not ideal. Combining study data did not provide sufficient evidence to recommend the use of colostrum for oral priming to prevent complications in preterm infants. Five of the included studies reported no harms (adverse effects); however, no numerical data are available from these studies. Included studies were of very low quality; therefore the effects of OPC remain uncertain. Larger, better quality clinical trials would be needed to evaluate more precisely and reliably the effects of OPC on important outcomes for preterm infants. .
We found 39 clinical trials involving 1897 children and 729 adults. Thirty-three of the trials were conducted in an emergency room (or emergency department) and community settings (such as a GP's surgery), and six trials were on inpatients (people in hospital) with acute asthma (207 children and 28 adults). Overall we judged the quality of the evidence to be moderate. Taking beta-agonists through either a spacer or a nebuliser in the emergency department did not make a difference to the number of adults being admitted to hospital, whilst in children we can be fairly confident that nebulisers are not better than spacers at preventing admissions. In children, the length of stay in the emergency department was significantly shorter when the spacer was used instead of a nebuliser. The average stay in the emergency department for children given nebulised treatment was 103 minutes. Children given treatment via spacers spent an average of 33 minutes less. In adults, the length of stay in the emergency department was similar for the two delivery methods. However the adult studies were conducted slightly differently which may have made it more difficult to show a difference in the length of stay in the emergency department. Because all the adult studies used a so-called "double-dummy" design, the adults received a spacer AND a nebuliser (either beta-agonist in a spacer and a dummy nebuliser or vice versa) which meant both groups of people were in the emergency department for as long as it took to take both treatments. Lung function tests were also similar for the two delivery methods in both adults and children. Pulse rate was lower in children taking beta-agonists through a spacer (mean difference -5% baseline), and there was a lower risk of developing tremor. Metered-dose inhalers with a spacer can perform at least as well as wet nebulisation in delivering beta₂-agonists in children with acute asthma, but we are less certain about the results in adults. The review is current as of February 2013.
We found eight trials with a total of 1183 participants to include in the review. Five trials provided CCT for three months, two for four months, and one for six months. We compared CCT with other activities, such as watching educational videos, and with no activity. We looked for effects on overall cognitive function and on specific cognitive functions, such as memory and thinking speed. All of the included studies had some design problems, which could have biased the results. Overall, we thought the quality of the evidence that we found was low or very low. This means we cannot be confident in the results, and that future research might well find something different. CCT may slightly improve overall cognitive function after 12 weeks of training; however, we found no evidence of a persistent effect 12 months after the intervention. We were unable to comment or found little evidence that CCT when compared with other activities may have a relevant effect on most of the specific cognitive functions that we examined. The longest trial found that compared to doing nothing, completing six months of CCT may have had a beneficial effect on memory. None of the included trials reported effects of cognitive training on quality of life or on daily activities, and none reported harmful effects of training. Compared to other activities, CCT may lead to slightly better overall cognitive function at the end of 12 weeks of training, but we found no evidence that the effect persists a year later. Compared to doing nothing, CCT may slightly improve memory at the end of six months of training. Although we excluded trials with less than 12 weeks of training, the trials that we included were still quite short for examining long-term effects as people age. A limitation of our review is that we did not include some trials with shorter training periods that did look for long-lasting effects, so it is possible that we missed some useful evidence. Many published studies have looked at computer training. Making sense of this substantial literature is difficult. It may be more helpful in the future to categorise trials by the duration of effects of training rather than by the duration of the training itself.
Authors from Cochrane Oral Health carried out this review and the evidence is up to date to 22 February 2018. A total of 50 randomised controlled trials were included with a total of 3704 participants. Within these studies 34 different sedatives were used, often with inhalational nitrous oxide as well. Dosages and delivery of these drugs varied widely. We grouped studies into those where drugs were compared to a placebo, where drugs were compared to other drugs or where different dosages of drugs were compared. Because all the studies were so different we could only carry out a meta-analysis for studies comparing oral midazolam to a placebo. The review showed that use of oral midazolam made patients more co-operative for dental treatment than a placebo drug. Where reported, adverse effects were few and minor. Oral midazolam probably improves behaviour of children during dental treatment. We evaluated other sedatives but there is insufficient evidence to draw any conclusions. There is some moderate-certainty evidence that midazolam administered in a drink of juice is effective.
In total, 66 studies (53 with quantifiable data, including 6013 participants; mean age 50 years) met the eligibility criteria for this review (current until August 2015). Moderate-quality evidence from 13 studies (involving 1245 people) suggests that phlebotonics reduce puffiness (oedema) compared with placebo. Low quality evidence suggests there is no difference in the proportion of healed ulcers with phlebotonics compared with placebo. For quality of life, it was not possible to combine all studies because of differences between the studies. However, individual phlebotonic treatments shows high quality evidence there is no difference in quality of life for the phlebotonic calcium dobesilate. Low-quality evidence revealed improvement of quality of life for aminaftone when compared to placebo. Furthermore evidence suggests phlebotonics have beneficial effects on trophic disorders, cramps, restless legs, swelling and tingling. However, the relevance of these findings to the overall clinical state remains unclear. Moderate-quality evidence from 33 studies (involving 3975 people) shows that phlebotonics produce more side effects, especially gastrointestinal disorders. Quality of the evidence The quality of evidence was downgraded because of selective reporting for the outcome ulcer healing, for incomplete outcome data for the outcomes ulcer healing, oedema and adverse events and for unclear randomisation and imprecision of the overall results for the outcome quality of life.
The evidence is current to 6 September 2016. We found one RCT that compared 38 people in the high-dose chemotherapy and transplantation group versus 45 people in the chemotherapy-only group and was judged to have mainly a low risk of bias (as it was well designed). The participants were 18 to 65 years old, had various types of nonrhabdomyosarcoma soft tissue sarcomas and were monitored for about 55 months. The treatment period ranged from 2000 to 2008. The single RCT was funded by a nonprofit organization (the funder did not benefit if the trial found good results). The results of the RCT did not favor either of the two treatment arms with respect to overall survival. There was one death related to treatment in the transplantation group and none in the chemotherapy-only group. There were eight cases of severe nonhematologic (not related to the blood) side effects in the transplantation group and one in the chemotherapy-only group. The overall quality of the data was unclear and based on only one RCT. Currently, research evidence is limited for the use of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for people with non-rhabdomyosarcoma soft tissue sarcomas. Further evidence is needed through well-designed clinical trials.
We searched for evidence (January 2019) and identified seven randomised controlled trials (RCTs), involving 831 women (range 36 to 226 women), conducted in high-income countries (USA, Denmark, Australia) between 2006 and 2015. Three trials only included women who were obese prior to pregnancy and four trials included women who were overweight and women who were obese. The trials compared different types of breastfeeding support to usual care. There were a limited number of trials for each type of support, and differences in how much support the women received in the support and usual care groups. One trial (39 women) used a physical support intervention through the loan of an electric or manual breast pump versus usual care (no pump). Very low-certainty evidence means it is unclear whether physical support improves exclusive breastfeeding at four to six weeks; or any breastfeeding at four to six weeks. The trial did not report other important outcomes of interest: non-initiation of breastfeeding, and exclusive or any breastfeeding at six months after birth. Six trials (792 women) used multiple methods of support (including education and social support through telephone or face-to-face contact) versus usual care. One trial (174 women) did not report on any of our main outcomes of interest. One of the trials also provided physical support through providing a breast pump and a baby sling, and another provided a small gift to the women at each trial visit. Support in these trials was provided by a professional (four trials) or a peer (two trials), either in a group (one trial) or individually (five trials). For women receiving an intervention that incorporated multiple methods of support (including social, educational or physical support) versus usual care, we are unclear about the effects of the intervention because we identified very low-certainty evidence for all of the important outcomes in this review: rate of non-initiation of breastfeeding; exclusive breastfeeding at four to six weeks; any breastfeeding at four to six weeks; rate of exclusive breastfeeding at six months after birth; and any breastfeeding at six months after birth. The effectiveness of interventions for supporting women who are overweight or obese to start and continue breastfeeding remains unclear. The methods used by the available trials varied in quality, with small numbers of participants. No trials compared one type of support to another. We need high-quality trials to evaluate whether social, educational, physical support, or any combination of these interventions can give mothers who are overweight or obese the best chance of starting and continuing to breastfeed. The interventions need to be designed specifically for this group of women and delivered by people who understand the challenges these women face when establishing and maintaining breastfeeding.
The review authors searched the literature and identified two controlled trials from the USA that involved 187 heroin addicts, aged 14 to 21 years; the participants were treated as outpatients. One study of 37 participants compared methadone with levo-alpha-acetylmethadol (LAAM) for maintenance treatment. After 16 weeks of maintenance treatment the adolescents were detoxified. The second trial of 150 adolescents compared buprenorphine and naloxone as maintenance treatment for nine weeks followed by tapered doses for up to 12 weeks with buprenorphine detoxification over 14 days. In the first trial methadone and LAAM led to similar improvements in social functioning. No side effects were reported. In the second trial the maintenance treatment seemed to be more effective in retaining patients in treatment but not in reducing the use of drugs of abuse. At one-year follow-up, self reported opioid use was clearly less in the maintenance group and more adolescents were enrolled in other addiction programmes. The most common side effect in both groups was headache. No participants left the study because of side effects. It is difficult to draw conclusions about the use of maintenance pharmacological interventions from only two trials. Conducting trials with young people may be difficult for both practical and ethical reasons. This review was limited by the very low number of trials retrieved. The quality of the evidence was very low for the comparison between methadone and LAAM and low for the comparison between buprenorphine detoxification and buprenorphine maintenance. The evidence is current to January 2014.
This review has identified all known trials that compared any kind of mechanical bowel preparation with no preparation (Comparison 1) and mechanical bowel preparation with rectal enema (Comparison 2) in patients submitted to elective colorectal surgery.  Five new trials have been included in this third update of the review, bringing the total number of included trials to 18 (5805 participants). Analysis of these 18 trials showed no statistically significant differences in how well the three groups of patients (mechanical bowel preparation group, no preparation group and rectal enemas) did after surgery in terms of leakage at the surgical seam of the bowel ends, mortality rates, peritonitis, need for reoperation, wound infection, and other non-abdominal complications.  Consequently, there is no evidence that mechanical bowel preparation improves the outcome for patients. Further research on mechanical bowel preparation or enemas versus no preparation in patients submitted for elective rectal surgery and laparoscopic colorectal surgery is warranted.
For this updated review, we included six trials with 9484 participants who were followed-up from one year to 4.7 years. We analyzed data to detect differences between lower and standard blood pressure goals in terms of numbers of deaths and numbers of serious adverse events (leading to hospital admission). We found no differences in total numbers of deaths, heart or vascular deaths, total heart problems, or vascular problems, nor in total serious harms, between lower and standard blood pressure goal approaches. Based on very little information, we found more dropouts resulting from drug-related harms in the lower blood pressure target group and no overall health benefit among people in the lower target group. The best available evidence does not support lower blood pressure goals over standard goals in people with elevated blood pressure and heart or vascular problems. More new trials are needed to examine this question. Overall, the quality of evidence was assessed as low to moderate according to the GRADE assessment.
Unfortunately, we did not find any good quality trials to include in the review. This does not mean that carnitine is ineffective or should not be used in treating inborn errors of metabolism; however, individuals receiving carnitine should be carefully observed and monitored. Therefore, we recommend that clinicians base their decision to prescribe carnitine on clinical experience together with individual preferences. Future trials should include patient-reported outcomes using validated and internationally recognised scales. Any adverse events associated with the treatment should be reported. It should be carefully considered whether placebo-controlled trials in potentially lethal diseases, e.g. carnitine transporter disorder or glutaric aciduria type I, are ethical.
This review included 29 randomised controlled trials involving 10,390 participants (current to September 2016), which compared LMWH or UFH for treating people with blood clots. Pooling the results of these trials showed that fewer participants treated with LMWH formed further blood clots and that fewer cases of bleeding occurred. Use of LMWH also reduced the size of the original blood clot when compared to the UFH group. There was no difference in number of deaths between participants treated with LMWH and those treated with UFH. Quality of the evidence Results of this review indicate that LMWH may prevent further blood clots and bleeding in people with VTE. However, these findings must be interpreted with caution due to the moderate quality of the evidence as a result of lack of reporting of study methods and problems with study design. Results indicating reduced size of blood clots when taking LMWH also must be interpreted with caution due to the low quality of evidence as results were not similar across the studies.
This review shows that a single intravenous infusion of infliximab (5 mg/kg) may be an effective treatment for patients with active Crohn's disease who no longer respond to corticosteroids or immunosuppressive drugs. There is also some evidence that CDP571, another TNF alpha blocking drug may be effective. There is no evidence to support the use of etanercept, a drug that blocks the action of TNF alpha by binding to receptors. There were no serious side effects associated with TNF blocking drugs, although the follow-up period of the studies reported in this review may have been too short to assess the development of serious side effects.
The evidence is current to May 2016. In this updated review, we identified 34 clinical trials that compared second-line therapy with either no chemotherapy (best supportive care) or an alternative second-line therapy, so addressing the issue of second-line therapy performance in people with metastatic colorectal cancer. Available evidence seemed to support the use of second-line therapy because it improved survival expectations as compared to best supportive care, although this was reported in only one small trial and the result would need to be confirmed in further research. Moreover, we found that modern chemotherapy regimens were more effective than older ones that contained a drug called 5-fluorouracil, that combination chemotherapy was more effective than single agent chemotherapy and that targeted agents (so called 'smart drugs' that attack the cancer cells and do little damage to normal cells) increased the effectiveness of conventional chemotherapy. Generally, toxicity increased as effectiveness increased. The main conclusions of this review were based on moderate to high quality evidence. When the quality of the evidence was considered low or moderate, this was generally due to inconsistency in the main results (i.e. the result for progression-free survival (time from the start of second-line treatment to progression of the cancer) was not confirmed by overall survival (time from the start of second-line treatment to death from any cause)) and the low numbers of participants included in the analyses. Nevertheless, it should be remembered that progression-free survival nowadays is considered a reliable surrogate of overall survival (which includes all deaths, not just cancer-related, and requires longer follow-up to obtain an accurate estimate) in the setting of second-line therapy for metastatic colorectal cancer. Most of the trials did not report quality of life, which prevented us formally investigating the balance between survival benefits provided by second-line systemic therapy and treatment-related toxicity.
To provide the best possible answer to this question, this review was conducted in a special preplanned way with the intention of putting together the results of all selected studies to produce an overall measure of the value of partial liquid ventilation. Two eligible studies (including a total of 401 participants) were found, and a comparison was made between those who received similar doses of perfluorocarbon and those who received traditional ventilation. No evidence indicated that partial liquid ventilation reduced the risk of death or the duration of artifical ventilation, and some evidence suggested that it may increase the risk of complications, including low blood oxygen levels, low heart rate, low blood pressure, air leakage from the lungs and cardiac collapse.
Trials which compared lower with higher amounts of sugar delivered by vein were too small to determine effects on the health outcomes of the babies. Insulin was found to reduce the number of babies who developed high blood sugar levels, but the health outcomes of the babies were not improved. In fact, insulin infusion was associated with an increased risk of death before 28 days of age.
Although many trials of these therapies exist, very few meet the scientific standards necessary to support the claims of beneficial effects in the therapies studied. This review identified nine randomized clinical trials, which tested eight different herbal medicines, compared with placebo, in HIV-infected individuals or AIDS patients with diarrhoea. The results showed that a preparation called SPV30 may be helpful in delaying the progression of HIV disease in HIV-infected people who do not have any symptoms of this infection. A Chinese herbal medicine, IGM-1, seems to improve the quality of life in HIV-infected people who do have symptoms. Another herbal compound ,SH, showed an increase of antiviral benefit when combined with antiretroviral agents. A South American herb preparation, SP-303, may reduce the frequency of abnormal stools in AIDS patients with diarrhoea. Other herbs tested were no better than placebo; however, the beneficial effects need to be considered with caution because the number of patients in these trials was small and the size of the effects quite moderate. In one trial the use of medicinal herbs was related to adverse effects such as gastrointestinal discomfort. Conclusion: No compelling evidence exists to support the use of the herbal medicines identified in this review for treatment of HIV infection and AIDS. To ensure that evidence is reliable, there need to be larger and more rigorously-designed trials.
The review looks at randomised controlled trials examining routine health promotion before pregnancy to see whether it changes behaviour and leads to improved health for mothers and babies. Four trials with 2300 women provided information for the review. The health promotion offered to women in these studies ranged from very brief advice on a specific topic through to more general advice and education on health and lifestyle over several sessions. In only one study were women followed up through pregnancy and there was little evidence of any differences between groups, although the babies of women who had received the health promotion intervention had slightly lower birthweights. There was some evidence that health promotion interventions encourage women to have more healthy lifestyles, such as lower rates of binge drinking. Overall, there was little evidence on the effects of pre-pregnancy health promotion on the health of mothers and babies, and more evidence is needed before its widespread implementation can be recommended.
This review searched for high-quality research studies that considered whether mobilizing community first responders could improve survival or neurological outcome, or both, following out-of-hospital cardiac arrest in adults and children. We last searched available databases in January 2019. We found two eligible research studies with a total of 1136 participants. One study conducted in Stockholm, Sweden, and funded by the Swedish Heart-Lung Foundation, Laerdal Foundation, and Stockholm County, found that mobilizing community first responders increased the rate of CPR performed before arrival of emergency medical services (data on 665 participants). The other study was conducted in Amsterdam and surrounding areas (the Netherlands) and was funded by the Netherlands Heart Foundation and Medtronic Physio-Control. Study authors reported that when community first responders were mobilized, more patients received defibrillation before emergency medical services arrived and survived to be admitted to hospital (data on 469 participants). Neither study found that dispatching community first responders resulted in significantly more overall survivors (data on 612 participants in one study and on 469 participants in the other). Neither study reported on the neurological function of survivors or on their health-related quality of life. Further research is needed to establish whether mobilizing community first responders can yield more survivors of cardiac arrest. Future research should consider both survival and the neurological function of survivors. The certainty of available evidence in terms of overall patient survival was considered low. The certainty of available evidence in terms of performance of CPR and defibrillation before arrival of emergency medical services and in terms of survival to hospital admission was considered moderate. This evidence is current to January 2019.
Cochrane Review authors collected and analysed all relevant randomised controlled trials (RCTs) to answer the review question. In RCTs people are allocated to treatment groups at random, which reduces bias. We found six eligible RCTs testing five different treatments in a total of 151 participants. We were uncertain about the evidence from the trials. One RCT with only 19 participants compared interferon beta-1a (a drug that is beneficial in multiple sclerosis) with placebo (a sham treatment). Another, with only 10 participants, compared a nerve growth factor which, in theory, should be beneficial in people with GBS, with placebo. A third trial, with 37 participants, compared cerebrospinal fluid filtration (washing the nerve roots around the spinal cord) with plasma exchange. A fourth trial with 43 participants compared the Chinese herbal medicine tripterygium polyglycoside, which is thought to have anti-inflammatory properties, with corticosteroids. A fifth trial with eight participants and a sixth with 34 participants compared eculizumab (a drug that blocks complement, a key inflammatory component) with placebo. Five trials received commercial company support. Support for the trial of the Chinese herbal medicine is unknown. None of these trials was large enough to confirm or refute the benefit or harm of any of these drugs in the treatment of people with acute GBS. The only trial that found a difference between treatments was the Chinese herbal medicine trial: participants receiving the herbal medicine were one and a half times more likely to have improved disability after eight weeks than those receiving corticosteroids. However, this estimate was uncertain and the trial authors did not report other clinical outcomes. Serious adverse events were uncommon with each of the five treatments investigated in the identified trials and rates were not different from those in the control groups. We identified very little evidence other than that from RCTs. There is a need to develop and test new treatments for GBS, and to adopt more sensitive outcome measures. The evidence is up to date to October 2019.
The bacterial infection of the urine often persisted, whether antibiotics were given or not. It was uncertain whether antibiotics prevented symptomatic urinary infection or increased the risk of selecting bacteria resistant to antibiotics, because there were too few data and several limitations in the included studies. Also, it was unclear whether the use of antibiotics in case of urinary infection without symptoms reduced the risks of graft rejection, need for hospitalisation due to symptoms of urinary infection, or mortality, or whether antibiotics improved the function of the kidney transplant. One study with 112 participants suggested there were no severe harmful reactions caused by the antibiotic treatment, and non-severe adverse events appeared to be rare. It is uncertain whether antibiotics are beneficial in kidney transplant recipients with bacteria in their urine but no symptoms. In one study, participants were assigned to antibiotics or no therapy by a method that was not random (i.e. according to patients' transplant code). In both studies, participants knew which treatment they were receiving (i.e. antibiotics or no therapy), which may have influenced the results. Last, we had not enough data to estimate with precision some effects of antibiotics. More research is needed.
We searched medical databases for studies in which neither participants nor researchers were told which treatment was given (called a randomised double-blind trial). The effectiveness and safety of IVIG were considered in terms of the occurrence of significant disability at six months after hospital discharge and the proportion of children experiencing at least one serious side effect. Up to 30 September 2016, only three studies comprising 138 children met the criteria to be included in this review. All three studies included only children with viral encephalitis. One study of Japanese encephalitis, a specific form of viral encephalitis, analysed both effectiveness and safety, and concluded that IVIG treatment had no additional beneficial effects when compared with placebo (pretend) treatment. The other two studies analysed other measurements, such as length of hospital stay, time to resolution of spasms, symptoms arising due to nerve damage, and time to regain consciousness and concluded that adding IVIG treatment was more effective than standard care alone when these outcomes were considered. The quality of the evidence was very low due to the small number of children and studies. The quality of evidence in the included studies was very low, making it impossible to draw any firm and definite conclusions on the clinical efficacy and safety of IVIG treatment for children with encephalitis. Furthermore, there was no information on funding while, for one study, the main authors' group was affiliated to the funding body: this is a well-known potential source of conflict of interest and thus of bias.
The evidence in this review, carried out through the Cochrane Oral Health Group, is up-to-date at 25 February 2015. We found eight studies that were suitable to include in this review. The studies involved a total of 2876 children from birth to 15 years of age who were at moderate to high risk of tooth decay. Six of the studies looked at the effects of dental professionals applying different strengths of chlorhexidine varnishes to the baby teeth, permanent teeth or both types of teeth in children and adolescents. The other two studies looked at the effects of parents placing chlorhexidine gel on their children's baby teeth. There were no studies that examined other products containing chlorhexidine, such as sprays, toothpastes, chewing gums or mouthrinses. The results did not provide evidence that chlorhexidine varnish or gel reduces tooth decay or reduces the bacteria that encourage tooth decay. The studies did not evaluate other outcomes such as pain, quality of life, patient satisfaction or direct and indirect costs of interventions. Four studies measured side effects and found none were observed. Due to the lack of suitable studies and concerns about possible bias in the included studies, the evidence is very low quality. As a result, we are not able to conclude whether or not chlorhexidine is effective in preventing tooth decay in children or adolescents, when compared to placebo (an inactive substitute for chlorhexidine) or no treatment. Future research on the use of chlorhexidine to prevent tooth decay is needed and should consider both primary and permanent teeth and should assess other chlorhexidine-containing products that can be used at home, such as toothpastes or mouthrinses.
In a previous review, we included 26 studies and we concluded that tailoring can change professional practice. However, more studies of tailoring have been published and therefore we have incorporated the new studies into an update of the review. We have included 32 studies in the new review. The findings continue to indicate that tailored interventions can change professional practice, although they are not always effective and, when they are, the effect is small to moderate. There is insufficient evidence on the most effective approaches to tailoring, including how determinants should be identified, how decisions should be made on which determinants are most important to address, and how interventions should be selected to account for the important determinants. In addition, there is no evidence about the cost-effectiveness of tailored interventions compared to other interventions to change professional practice. Therefore, future research studies should seek to develop and evaluate more systematic approaches to tailoring.
Four trials, involving a total of 237 participants, were included in the review. These trials had methodological weaknesses that could have resulted in serious bias. One trial compared 'short arm' (splintage stopping below the elbow) pre-fabricated functional braces with 'long arm' (splintage includes the elbow) plaster casts. It found no clear difference between the two groups in the time taken for the fracture to heal. However, significantly more people in the brace group were satisfied with their treatment and significantly more returned to work during their treatment. One trial compared Ace Wrap elastic bandage, short arm plaster cast and long arm plaster cast. The large loss to follow-up in this trial makes any findings tentative. However, the need for replacement of the Ace wrap by other methods due to pain does indicate the potential for a serious problem with this intervention. The third trial, which compared immediate mobilisation versus short arm plaster cast versus long arm plaster cast for minimally displaced fractures, found no clear differences in outcome between these three interventions. The fourth trial found no significant differences in functional or anatomical outcomes nor complications between the two types of plates used for surgical fixation of the fracture. Overall, there was not enough evidence from randomised controlled trials to show which methods of treatment are better for these injuries.
Follicle-stimulating hormone (FSH) - a relatively expensive drug - is commonly used for several days to stimulate the ovaries of women undergoing assisted reproduction. Initial studies have shown that after a few days of using FSH to stimulate the ovaries, it can be replaced by human chorionic gonadotropin (hCG), which is less expensive. In addition to cost reduction, this intervention has a theoretical potential to reduce the risk of ovarian hyperstimulation syndrome (OHSS); though the underlying risk is already very low for most women. We searched the medical literature on in February 2013 for studies that evaluated the effectiveness and safety of using low-dose hCG to replace FSH during the late follicular phase in women undergoing controlled ovarian hyperstimulation (COH) for assisted reproduction, compared to the use of a conventional COH protocol. Five studies evaluating 351 women were included in this review. These studies were funded by fertility centres, universities, or both. We are very uncertain of the effect of this intervention on live birth, OHSS and miscarriage When use of low-dose hCG to replace FSH was compared with conventional COH, there was very low quality evidence compatible with appreciable benefit, no effect or appreciable harm for the intervention, suggesting that for women with a 14% chance of achieving live birth using a conventional COH, the chance of achieving live birth using low-dose hCG would be between 10% and 45%. Similarly, there was very low quality evidence suggesting that for women with a 3% risk of OHSS using a conventional COH, the risk using low-dose hCG was also compatible with either benefit or harm, and would be between 0% and 4%. Additionally we observed that there was low quality evidence suggesting that for women with a 32% chance of achieving ongoing pregnancy using a conventional COH, the chance using low-dose hCG was compatible with either benefit or no effect, and would be between 27% and 53%. There was low quality evidence suggesting that for women with a 35% chance of achieving clinical pregnancy using a conventional COH, the chance using low-dose hCG was compatible with either benefit or no effect, and would be between 32% and 54%. There was very low quality evidence suggesting that for pregnant women with a 16% risk of miscarriage using a conventional COH, the risk using low-dose hCG was compatible with either benefit or harm, and would be between 8% and 36%. We also observed that there is moderate-quality evidence that this intervention reduces the total FSH consumption and is unlikely to materially affect the number of oocytes retrieved Our conclusions are that we are very uncertain of the effect on live birth, OHSS and miscarriage of using low-dose hCG to replace FSH during the late follicular phase of COH in women undergoing ART, compared to the use of conventional COH. The current evidence suggests that this intervention does not reduce the chance of ongoing and clinical pregnancy; and that it is likely to result in an equivalent number of oocytes retrieved expending less FSH. More studies are needed to strengthen the evidence regarding the effect of this intervention on important reproductive outcomes.
We searched for studies that investigated the effect of introducing a ban on any measures of health, or on smoking behaviour (up to February 2015). Since the previous version of this review had shown clear evidence that introducing legislation to ban smoking in public places does reduce exposure to secondhand smoke (SHS) in those places, we did not include studies that only reported exposure to SHS. We included 77 studies from 21 countries in this updated review. Studies of health outcomes typically used data from hospitals to look for changes in rates of admissions, discharges or deaths. Most studies looked at illnesses related to the cardiovascular system (heart or blood vessels), such as heart attacks and strokes. Studies also looked at effects on respiratory health, including chronic obstructive pulmonary disease (e.g. bronchitis), asthma and lung function. Seven studies looked at the health of newborn children. Eleven studies reported death rates. The best-quality studies collected data at multiple time points before and after the introduction of a ban in order to adjust for existing time trends. Some studies could compare events rates in areas with and without bans, or where bans were introduced at different times. Key results There is evidence that countries and their populations benefit from improved health after introducing smoking bans, importantly to do with the heart and blood vessels. We found evidence of reduced deaths. The impact of bans on respiratory health, on the health of newborn children, and on reducing the number of smokers and their cigarette use is not as clear, with some studies not detecting any reduction. Quality of the evidence Legislative bans have not been evaluated by randomized trials, and the quality of the evidence from the types of studies contributing to this review is lower. Changes in health outcomes could be due to other things, such as change in healthcare practices. However, many of the studies used methods of analysis that could control for underlying trends, and increase our confidence that any changes are caused by the introduction of bans.
We performed a thorough search for studies that reported the accuracy of EUS or MRCP in the diagnosis of CBD stones. We included a total of 18 studies involving 2532 participants. Eleven studies evaluated EUS alone, five studies evaluated MRCP alone, and two studies evaluated both tests. A total of 1537 participants were included in the 13 studies that evaluated EUS and 995 participants were included in the seven studies that evaluated MRCP. Most studies included patients who were suspected of having CBD stones based on abnormal blood tests, abnormal ultrasound, or symptoms such as jaundice or pancreatitis, or a combination of the above. The proportion of participants who had undergone previous gallbladder removal varied across studies. Based on an average sensitivity of 95% for EUS, on average 95 out of 100 people with CBD stones will be detected while the remaining 5 people will be missed and will not receive appropriate treatment. The average number of people with CBD stones detected using EUS may vary between 91 and 97 out of 100 people. The average specificity of 97% for EUS means that on average 97 out of 100 people without CBD stones will be identified as not having CBD stones; 3 out of 100 would be false positives and would not receive appropriate treatment. The average number of false positives could vary between 1 and 6 out of 100 people. For MRCP, an average sensitivity of 93% means that on average 93 out of 100 people with CBD stones will be detected while the remaining 7 people will be missed and will not receive appropriate treatment. The average number of people with CBD stones detected using MRCP may vary between 87 and 96 out of 100 people. With an average specificity of 96% for MRCP, 96 out of 100 people without CBD stones will be identified as not having CBD stones; 4 out of 100 would be false positives and would not receive appropriate treatment. The average number of false positives could vary between 2 and 10 out of 100 people. This means that some people with CBD stones can be missed by EUS and MRCP. Although most people with a negative EUS or MRCP do not need to undergo further invasive tests, in the presence of persistent symptoms further testing with MRCP if the patient had undergone EUS or EUS if the patient had undergone MRCP, ERCP, or IOC may be indicated. There is little to choose between EUS and MRCP in terms of diagnostic accuracy. All the studies were of low methodological quality, which may undermine the validity of our findings. Further studies of high methodological quality are necessary.
We searched major medical databases for studies that have examined the use of lamotrigine for people with schizophrenia. We identified five relevant studies that were conducted according to existing standards of research. A total of 537 people with schizophrenia participated in these five studies. The participants were resistant to various degrees to usual treatments and were randomised to receive either lamotrigine or placebo in addition to their usual drugs. The data regarding effectiveness could only be usefully analysed in less than 70 participants. Lamotrigine was considered to be effective if the questionnaire scores showed a greater reduction than for those who received placebo. The magnitude of this effect was small when compared to placebo. Data regarding adverse effects were available from three studies. There was a higher occurrence of nausea in those receiving lamotrigine. Apart from this the common side effects were headache and dizziness. The current evidence does not suggest that the addition of lamotrigine is a remarkable strategy for people with resistant schizophrenia, but the results are suggestive of a positive effect on the symptoms of schizophrenia. However, more studies with larger number of participants are needed to confirm the true magnitude of benefit and safety. This review is limited by the poor presentation of data from the individual studies.
We included 23 trials with 2656 people who either had a stent or not. Whether they received a stent or not was decided by chance. A stent may make people come back to the hospital for problems less often, but we are very uncertain of this finding. Pain on the day of surgery and on days one to three after surgery may be similar. People with a stent may have more pain in the long term (days four to 30), but we are also very uncertain about this. The need for another procedure may be similar. People with a stent may be less likely to need narcotics (strong pain medications that can cause addiction), but we are very uncertain about this. There may be no difference in the risk of a urinary tract infection. Stenting may make people a little less likely to develop a narrowing of the ureter because of scarring and may make them slightly less likely to be admitted to the hospital. However, we are very uncertain of both findings. The certainty of evidence ranged from moderate to very low depending on the outcome, meaning that we have moderate, low, or very low confidence in the study results.
Trials comparing ipratropium bromide versus beta-agonists showed no significant difference in short-term or long-term effects (24 hours) on ease of breathing. Side effects of these drugs were reported by only a minority of patients and include dry mouth and tremor, and a 'strange feeling' after drug administration.
We searched scientific databases for clinical trials comparing exercise to no exercise or other treatments in adults with MS. The evidence is current to October 2014. We found 45 trials, involving 2250 people with MS, assessing the effect of exercise therapy using self reported fatigue. We used 36 studies, involving 1603 people with MS, in an analysis. Combined, these 36 trials supported the idea that exercise therapy may be a promising treatment to reduce fatigue without side events. This finding seems especially true for endurance training, mixed training (i.e. muscle power training mixed with endurance training), or 'other' training (e.g. yoga, tai-chi). To assess the safety of exercise therapy we counted the number of reported MS relapses in the people receiving exercise therapy and in people in a non-exercise group and did not find a significant difference. Even though these results are promising, it is worth noting some methods used in the trials may have affected the reliability of the results. For example, most trials included a low number of participants and did not primarily aim to reduce fatigue (but, for instance, aimed to improve walking capability) with the assessment of fatigue being a secondary measure. However, in contrast, exercise therapy may also be less feasible for people with MS who are severely fatigued. In addition, the reporting and definition of MS relapses was in general poor, and lacked consistency. Future, high-quality research is warranted to elucidate the feasibility, effects, and working mechanisms of exercise therapy. Future studies may benefit from a uniform definition of fatigue, and subsequently be designed to measure fatigue specifically.
To investigate this question we looked for randomised controlled trials (RCTs), these are studies in which people involved have an equal chance of receiving the treatment or comparator. We were interested in trials that compared different flow rates (concentrations) of oxygen delivered in an ambulance to people being transferred to hospital because of sudden worsening of COPD symptoms. Only one study was found that addressed the review question. The study randomised participants to either have titrated oxygen (oxygen therapy delivered at different concentrations tailored to patient needs in order to keep the levels of oxygen in the blood between 88% and 92%) or high-flow oxygen (oxygen therapy delivered at a consistently high concentration). There were fewer deaths (two people) in the group that received titrated oxygen, compared to the control group using high-flow oxygen delivered at eight to ten litres per minute using a mask (11 people). Due to inclusion of only one study, and the small number of deaths that occurred, our confidence in the size of the difference between the two treatments is limited. We judged the evidence to be of low certainty. The one included study found that delivering individually tailored oxygen concentrations to people when they are being transported to hospital with sudden worsening of COPD, reduces the risk of death compared to using a consistently high concentration of oxygen. However, the body of evidence is too small to confidently claim that titrated oxygen is less harmful and more effective than high-flow oxygen in this group of people across the board. This plain language summary is current to September 2019.
Aerobic exercise is physical activity that stimulates a person's breathing and blood circulation. The review of 14 trials, involving 1014 pregnant women, found that pregnant women who engage in vigorous exercise at least two to three times per week improve (or maintain) their physical fitness, and there is some evidence that these women have pregnancies of the same duration as those who maintain their usual activities. There is too little evidence from trials to show whether there are other effects on the woman and her baby. The trials reviewed included non-contact exercise such as swimming, static cycling and general floor exercise programs. Most of the trials were small and of insufficient methodologic quality, and larger, better trials are needed before confident recommendations can be made about the benefits and risks of aerobic exercise in pregnancy.
The people included in the studies were adults over 18 years of age in outpatient settings, for whom lipid-lowering therapy was recommended. We now include 35 studies covering 925,171 participants in this review. Of the 35 included studies, 16 compared interventions categorised as 'intensified patient care' versus usual care. These interventions included electronic reminders, pharmacist-led interventions, and healthcare professional education to help people better remember to take their medications. These types of interventions when compared to standard care demonstrated significantly better adherence rates both over the short term (up to and including six months) as well as the long term (longer than six months). Additionally, cholesterol levels were better over both long- and short-term periods in those offered the intervention, compared to those receiving usual care. We considered only randomised controlled trials for this review. Given the nature of the interventions, it was not possible to keep participants unaware of which group they were in. However, analysis of other forms of bias indicated that generally the studies were at low risk of bias. We assessed the evidence for the outcomes using the GRADE system, and rated it as high quality for long-term adherence (more than six months) and for reduction in total cholesterol, and moderate quality for short-term medication adherence (up to six months) and for LDL-cholesterol levels. For the outcome total cholesterol levels at less than six months follow-up, we downgraded the evidence to low quality.
Early studies suggested a beneficial effect of ALC on cognition and behaviour in aging subjects. However, later, larger studies have not supported these findings. The early and later studies differ widely in methodology and assessment tools used, and are therefore difficult to compare. There is no evidence of benefit of ALC in the areas of cognition, severity of dementia, functional ability or Clinical Global Impression as a continuous measure. An apparent beneficial effect on Clinical Global Impression assessed as a dichotomous variable may be due to chance. There was also a significant treatment effect on the Mini Mental State Examination (MMSE) at 24 weeks, but this result must be interpreted with caution in the context of significant heterogeneity in these trials. ALC is not currently in routine clinical use.
We summarized trials that compared the World Health Organization (WHO)-recommended primaquine regimen of 15 to 30 mg per day for 14 days with the same or higher doses of primaquine given over different lengths of time to determine whether alternative regimens were as successful as the recommended courses at preventing future episodes of P vivax malaria. We searched for trials up to 17 December 2018, and included nine randomized controlled trials (studies in which participants are assigned to one of two or more treatment groups in a random manner) in our analysis. When using 30 mg per day compared to 15 mg per day primaquine therapy for 14 days, we do not know if there is any difference in P vivax recurrences at 6 months (very low-certainty evidence). No serious side effects were reported, but it is unclear whether or not there is a difference in other side effects between doses (very low-certainty evidence). When using 30 mg primaquine per day for 7 days compared to 15 mg per day for 14 days, there may be no difference in P vivax recurrences at 6 to 7 months (low-certainty evidence). No serious adverse events were reported. There may be no difference in the number of side effects known to occur with primaquine between the two treatment regimens (low-certainty evidence). We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to the 14-day regimen at 11 months' follow-up (very low-certainty evidence). Further large high-quality RCTs are needed, such as the IMPROV trial, to help improve the certainty of the evidence around alternative regimens. How up-to-date is this review? The review authors searched for studies up to 17 December 2018.
We found two studies. The first study compared the removal of fibroids versus no removal in 94 women wishing to become pregnant spontaneously from January 1998 to April 2005. The second study compared the removal of polyps versus simple hysteroscopy only in 204 women before insemination with husband's sperm from January 2000 to February 2004. The evidence is current to April 2018. Neither study reported funding sources. In women with fibroids wishing to become pregnant spontaneously we were uncertain whether removal of the fibroids improved the pregnancy or miscarriage rate compared to usual management: uncertainty remains because the number of women (94) and the number of pregnancies (30) were too small and the quality of the evidence was very low. We found no data on live birth or complications due to surgery. We found no studies on women with polyps, septa or adhesions. The hysteroscopic removal of polyps prior to intrauterine insemination (IUI; a fertility treatment where sperm is placed inside a woman's womb to fertilise the egg) is may improve the pregnancy rate compared to not removing polyps. If 28% of women become pregnant without surgery, the evidence suggests that about 63% of women will become pregnant following removal of polyps. We found no data on number of live births, hysteroscopy complications or miscarriage rates prior to IUI. We retrieved no studies in women before other fertility treatments. More studies are needed before hysteroscopy can be proposed as a fertility-enhancing procedure in the general population of women having difficulty becoming pregnant. The quality of the evidence retrieved was very low to low due to the limited number of participants and the poor design of the studies.
We identified three trials. Two trials with 100 participants provided information on one or more outcomes (measures of how well the treatments worked). The trials compared phlebotomy (removal of blood or 'blood letting') versus erythrocytapheresis (removal of blood, separation of red cells (which carry oxygen in the blood), and return of the remaining parts of the blood). Two trials were conducted in people who had not undergone previous treatment for haemochromatosis. The trial that provided most data for this review excluded people with cancer, heart failure, and serious irregular heartbeats. Source of funding: the two trials that provided data for this review were funded by parties with no vested interest in the results; the source of funding of the third trial was not reported. There were no deaths or serious complications in the short term in either group in the only trial that reported this information. There was no evidence of any difference in the percentage of people with any complications, the number of complications per person, and short-term health-related quality of life (a measure of a person's satisfaction with their life and health) between the treatments. None of the trials reported deaths beyond one year, health-related quality of life beyond one year, liver transplantation, severe liver damage, liver failure, liver cancer, diabetes, heart failure, or stroke during the long term. There is currently insufficient evidence to determine whether erythrocytapheresis is beneficial or harmful compared with phlebotomy. Erythrocytapheresis requires special equipment, while phlebotomy does not. So, phlebotomy remains the treatment of choice in people with hereditary haemochromatosis even though there is no evidence from randomised clinical trials that blood letting is beneficial. Having said this, a randomised clinical trial including no treatment is unlikely to be conducted. The overall quality of evidence was very low as the trials were at high risk of bias, which means that there is possibility of making wrong conclusions overestimating benefits or underestimating harms of treatments because of the way that the studies were conducted. Further high-quality randomised clinical trials to identify how often blood letting should be performed and those comparing erythrocytapheresis versus blood letting are required. Such trials should include long-term monitoring of participants (perhaps by linking health records in some countries).
We carried out a comprehensive search for randomised controlled trials (RCTs) in participants diagnosed with Frey's syndrome. We planned to include trials in which participants received any intervention compared to no treatment (observation) or an alternative intervention, with or without a second active treatment. Despite extensive searching, we were unable to identify any studies that met our inclusion criteria. There is no high-quality evidence to establish which type of treatment is most effective for the treatment of Frey's syndrome. High-quality clinical trials in this area should be urgently conducted. Studies should investigate all possibly effective treatments (such as anticholinergics, antiperspirants and botulinum toxin) compared to control groups using different treatments or placebo. Subjective (patient) assessment of Frey's syndrome should be one of the outcome measures used. This review is up to date to 28 April 2014.
We examined a total of 16 controlled clinical studies using aromatherapy for PONV with a total of 1036 participants (seven new studies from the March 2017 searches were added to nine studies from the original review). The participants were adults except for two studies in children. The studies applied aromatherapy at the first complaint of nausea in the immediate period after surgery and measured nausea for up to two days. Aromatherapy substances used were isopropyl alcohol (rubbing alcohol), peppermint oil, ginger, or mixtures that included ginger, spearmint, peppermint and cardamom; or lavender, peppermint, ginger, and spearmint oils. The studies compared aromatherapy to saline or water placebo, controlled breathing, other aromatherapy substances, anti-nausea medications, or a combination of these, with some studies having up to four groups. Overall, aromatherapy was not effective in reducing nausea severity at greater than three minutes after treatment in comparison to saline, water or controlled breathing placebo (6 studies with 241 participants) but more participants who received aromatherapy were nausea-free at the end of treatment (4 studies, 193 participants) and fewer participants who received aromatherapy required anti-nausea medications (7 studies with 609 participants). Peppermint oil did not show an effect on nausea severity at five minutes after treatment (4 studies, 115 participants). We could not pool data for a comparison of isopropyl alcohol to standard anti-nausea medications for nausea severity. In terms of nausea duration, the time to 50% relief of symptoms was faster with isopropyl alcohol vapour than with standard antiemetics (ondansetron and promethazine) (3 studies, 176 participants). Aromatherapy using isopropyl alcohol vapour inhalation provided rapid, short-term relief of nausea and reduced the need for rescue anti-nausea drugs (4 studies, 215 participants). Patient satisfaction with aromatherapy appeared high in the four studies that measured this outcome. Fewer participants who received isopropyl alcohol aromatherapy required rescue anti-nausea drugs compared with those who received saline (4 studies, 291 participants). The participants receiving aromatherapy were not more likely to be free of nausea at the end of the treatment period however they were less likely to require rescue anti-nausea drugs. All participants in these studies (treatment and comparison groups) reported high levels of satisfaction, possibly indicating that increased attention to the care of postoperative nausea and vomiting improved satisfaction with their care. Aromatherapy may provide a useful therapeutic option, particularly when the alternative is no treatment at all. None of the included studies reported adverse effects from the aromatherapies used. Overall the evidence quality ranged from moderate to very low, as assessed by GRADE. There was a high risk of bias due to the design of some studies. The included studies consisted of 12 randomized controlled trials and 4 controlled clinical trials where participants were not randomly assigned to a treatment group. In most studies, participants and researchers were aware of group allocation and this may have had an influence on the results. The strong odours involved meant that aromatherapy was a difficult intervention to conceal from participants, research staff and those assessing outcomes. The different comparisons, time points and measurement scales limited the data that could be pooled. Some data were expressed as standardized scales and measures, which enabled pooling of results in meta-analyses. The data were incomplete for effects longer than 60 minutes.
Nine studies involving 1359 participants met the inclusion criteria. Six studies compared individual education to usual care and three compared individual education to group education (361 participants). There were no long-term studies and overall the quality of the studies was not high. Individual face-to-face patient education for type 2 diabetes over a six to twelve month period did not significantly improve glycaemic control, body mass index (BMI - measure of overweight; body weight in kilogram divided through squared height in meters, kg/m2), blood pressure or total cholesterol in the short or medium term compared with usual care. However, there did appear to be a significant benefit of individual education on glycaemic control in a subgroup analysis of studies involving participants with a higher baseline HbA1c greater than 8% (that is, too high blood sugar levels over a couple of months or inadequate 'metabolic control'). In the studies comparing individual education to group education, there was no significant difference between individual or group education at 12 to 18 months nor a significant difference in the impact of individual education versus group education on BMI, systolic or diastolic blood pressure. An exact analysis on dietary self management, diabetes knowledge, psychosocial outcomes and smoking habits could not be performed because there were limited studies and varied measurement tools. However, descriptive evaluation suggested that there was no significant difference in quality of life, self management skills or knowledge between group and individual education. When comparing individual patient education to usual care, the limited number of studies available suggested a positive outcome on self management, smoking and knowledge, however there was conflicting evidence surrounding psychosocial outcomes. No data were available on the other main outcome measures of diabetes complications or health service utilization and cost analysis in these studies.
Ten trials including 657 patients were included in this review. All were of high risk of bias (systematic error) and play of chance (random error). Only one or two trials were included under each comparison. There was no difference in mortality, liver failure, or post-operative complications between any of the comparisons. Hepatic vascular occlusion does not decrease the blood transfusion requirements. It decreases the cardiac output (amount of blood pumped by the heart in one second) and increases the systemic vascular resistance (resistance to the flow of blood in the vessels), which may have potential problems in patients with heart disorders. Although there was no statistically significant difference in the incidence of liver failure between continuous portal triad clamping and intermittent portal triad clamping (5/60; 8.5% versus 0/61), most of them occurred in patients with chronic liver diseases undergoing the liver resections using continuous portal triad clamping. There was no benefit in selective inflow occlusion compared to portal triad clamping. There was no statistically significant difference in the incidence of liver failure between the two groups (4/41; 9.8% versus 0/39), but all patients with liver failure occurred in the selective inflow occlusion group. There were no significant differences in any of the important outcomes between the different methods of intermittent portal triad clamping or between ischaemic preconditioning followed by continuous vascular occlusion and intermittent vascular occlusion in non-cirrhotic patients undergoing liver resections. Further randomised trials of low risk of bias are needed to determine the optimal technique of vascular occlusion.
Authors from Cochrane Oral Health carried out this review and the evidence is up to date from 22 July 2014. Eight trials were included with a total of 233 extraction sites (teeth taken out) in 184 participants. Participants were adults aged 18 years or older, in good general health, needing one or more permanent teeth to be taken out and the consideration of the use of ARP (alveolar ridge preservation techniques) with the possibility of using dental implants at a later date. The review looked at the effects of four techniques and materials used for preserving the tooth extraction socket. Three studies compared socket preservation to tooth extraction alone, while five studies compared two or more different materials. There is limited evidence that socket preservation (ARP) can reduce bone loss compared to tooth extraction alone to allow for dental implant placement. There is no evidence that socket preservation makes any important differences to the look or lasting quality of crowns or bridges. There is no convincing evidence of any significant difference between different materials and barriers used for socket preservation. The quality of the evidence is judged as low due to high risk of bias of the majority of the included studies. Some evidence of reporting bias is suspected, as only two of the included trials did not receive any industry support. Further long-term randomised controlled trials that follow CONSORT guidelines (www.consort-statement.org) are required.
In people with central nervous system lupus: - We are uncertain whether cyclophosphamide improves signs and symptoms or disease activity compared to methylprednisolone. - No differences between the two groups were found in tissue or organ damage, or in the number of monthly seizures, but this may have happened by chance. - After six months of treatment, people who took cyclophosphamide took fewer prednisone pills than people who took methylprednisolone. - And at the end of two years, more people who took cyclophosphamide stayed on their treatment than people who took methylprednisolone. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Side effects, such as infections, high blood sugar and high blood pressure, pancreas problems and death occurred about the same amount in people who took cyclophosphamide or methylprednisolone. Systemic lupus erythematosus (SLE) is a disease in which the body's immune system attacks the body. In CNS lupus (central nervous system lupus) the body may have attacked and damaged the cells in the brain and spine. This damage may cause a person to have convulsions/seizures, chronic headaches, confusion and psychosis. Drugs such as corticosteroids (prednisone or methylprednisolone) are usually used for lupus to decrease inflammation and control the immune system. Immunosuppressive agents or cytotoxics such as cyclophosphamide (CTX or Cytoxan) may also be used. - 49 more people who took cyclophosphamide improved than people who took methylprednisolone. - 95 out of 100 people had at least a 20% improvement in symptoms with cyclophosphamide. - 46 out of 100 people had at least a 20% improvement in symptoms with methylprednisolone.
The evidence is current to February 2016. We included only randomised clinical trials, as they are considered to be the best type of scientific study to answer questions about treatment, that compared the survival of women undergoing breast surgery combined with medical treatment versus medical treatment alone. We identified and included two randomised controlled trials involving a total of 624 women: 311 women underwent breast surgery plus medical treatment, and 313 women only received medical treatment. The review authors are uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low. The included studies did not report any information relating to quality of life. Breast surgery may improve the control of local disease but it probably worsened control at distant sites. The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy appeared to be the same in the group undergoing breast surgery combined with medical treatment and in the group receiving only medical treatment. It is not possible to make definitive conclusions about the benefits of breast surgery associated with medical treatment for women with metastatic breast cancer. The decision to perform surgery in such cases should be individualised and shared between the physician and the patient, considering the potential risks and benefits involved in this choice. The inclusion of results of ongoing trials involving women with these characteristics in the next update of this review will help to decrease existing uncertainties.
The evidence is current to August 2014. We included eight clinical trials of 952 participants. The trials assessed many different medicines at different doses, but only three trials included a placebo group (dummy medication). Six of these trials were of high quality, with low risk of error (i.e. bias, where the true effect is exaggerated). For this review, we included the effects of the medicines on nausea and vomiting up to one hour after the medicine was given. The main results of interest were the effect on nausea between zero and 60 minutes after the medicine was given, number of vomits and side effects to medicines. Of these, only nausea at 30 minutes and side effects were reported by all trials. From all trials, only one medicine was reported to be better than placebo and other medicines. That was droperidol, which was included in one small trial of 97 participants. No other single medicine was definitely better than any other medicine, and none of the other trials that included a placebo group showed that the active medicines definitely worked better than the placebo. Side effects were mild. Our results suggest that in people in the emergency department, nausea will generally improve, whether they are treated with specific medicines or placebo. Therefore, supportive treatment, such as intravenous fluids (where fluid is given directly into a blood vessel) may be sufficient for many people. Overall, the quality of the evidence was low, mainly because there was not enough data.
We identified only two small trials comparing clonazepam with a different drug in two different epileptic syndromes, mesial temporal lobe epilepsy (the most common and well-defined focal epilepsy with seizures originating in the internal part of the temporal lobe of the brain) and absence seizures (generalized seizures causing lapses of awareness). In the study conducted in mesial temporal lobe epilepsy, clonazepam was compared to carbamazepine (an antiepileptic drug used to treat focal epilepsy). In the study on absence seizures, clonazepam was compared to ethosuximide (a medication used to treat absence seizures). We judged both studies as being of poor quality. The studies did not follow the participants for long enough, and the total of participants was too low to draw definite conclusions on the role of clonazepam used in monotherapy. Results on tolerability were not reported consistently across the studies. No differences were found between clonazepam and carbamazepine in the proportion of seizure-free participants; however, this does not mean that clonazepam and carbamazepine have the same efficacy, as the lack of difference can be due to the small number of people included. The study comparing clonazepam with ethosuximide provided no results on efficacy. No differences were found between the two medications in terms of tolerability. However, the proportion of people who dropped out or withdrew from the study due to side effects, lack of efficacy or other reasons was higher in the clonazepam group compared to the ethosuximide group. So far, the evidence on the efficacy and tolerability of clonazepam used as a single antiepileptic drug for the treatment of epilepsy is scarce and of very low certainty; hence insufficient to base decisions on its use in monotherapy.
We identified only four studies that compared different antibiotic regimens. They included a limited number of people. Each trial investigated different types and doses of antibiotics. These studies were published between 1998 and 2006 and were conducted in the USA, Spain and Finland. The evidence is up to date as of 30 April 2015. One study showed imprecise results on all-cause mortality (dead from any cause). One study suggested that one antibiotic regimen was superior to another (cloxacillin plus gentamycin was superior to either vancomycin or teicoplanin plus gentamycin). Two studies did not show any difference between the antibiotic regimens. In terms of the need for cardiac surgery, uncontrolled infection or relapse from endocarditis the knowledge is imprecise. No trials assessed septic embolic complications (when infection travels around the body and causes infection in other areas, such as the spine, eyes or lungs) or quality of life. We do not know how safe these medicines are. The confidence in the results of this review is very low. Current evidence does not support or reject any regimen of antibiotic therapy for the treatment of infective endocarditis. The studies had limitations in the way they were designed and performed, and three were sponsored by the manufacturer of the medicine that was assessed. Moreover, the limited number of people included in the studies led to uncertain results. Larger studies are required to provide more information about the best antibiotic regimens to treat people with infective endocarditis.
We looked for evidence up to November 2015. We included 14 randomized studies (involving 565 participants). Thirteen studies compared people who received normal care with additional intravenous amino acids against people who received normal care but no amino acids (the control group). One study compared people who received fructose with those in a control group. Studies involved adults undergoing planned or emergency surgery. We did not include studies in which participants were deliberately kept cold during surgery, were receiving skin grafts or were under local anaesthetic. We can be certain that at the end of surgery, people receiving intravenous nutrients are up to a half-degree warmer than people receiving control (based on evidence from six studies involving 249 participants). However, there was more uncertainty about the effects of intravenous nutrients at other time points, with some studies suggesting that intravenous nutrients keep participants warmer and other studies reporting that participants were colder than those receiving the control. We are uncertain if keeping people up to half a degree warmer is important to those involved in caring for people who are having surgery. We are also uncertain if giving intravenous nutrients reduces the risk of people shivering (based on evidence from three studies involving 155 participants). Most of the evidence was moderate to low in quality. The methods used to assign participants to treatment groups was often inadequate or unclear, and we were uncertain if the people assessing outcomes were aware of which treatment group participants were in. This may have biased the results, but we are unsure what effect it may have had on results overall.
The review of 10 studies (786 patients) found that mupirocin ointment reduced the risk of patients developing catheter-related bacteraemia (bacteria in the blood). However, monitoring of mupirocin resistance needs to be considered in future studies. There was not enough evidence to determine which ointment (povidone-iodine and polysporin) or dressing was the best in preventing infection. There was also insufficient evidence to support the use of medicinal honey for the prevention of infection.
The review authors searched the medical literature and found a single trial that met the inclusion criteria of the review. Sixty-three participants with lower eyelid entropion were enrolled and randomised to either everting sutures alone or everting sutures and a lateral tarsal strip. Eight participants were lost to follow-up. The trial showed that the combination of horizontal and vertical eyelid tightening with everting sutures and lateral tarsal strip is highly efficient for entropion compared to vertical tightening with everting sutures alone. Further research is needed to provide more credible evidence for the comparison of surgical treatments to correct an inward turning eyelid.
Only randomised controlled trials (RCT) were eligible for this review. In RCTs the patients are assigned to each of the groups in a random fashion so as to reduce the potential for bias. Either one group of patients had swallowing therapy, the other had a sham treatment or no treatment, or two forms of swallowing therapy were compared to each other. There were no controlled trials, randomised or otherwise, in this field. Therefore there is no trial evidence to prove or disprove the benefit of swallowing therapy for the treatment of swallowing disorders in people with Parkinson's disease. It should be emphasised that this lack of evidence does not mean lack of effect. There is one large RCT currently recruiting patients that will compare 'chin down' posture with thickened liquids in the treatment of dysphagia. The main outcomes in this study will be the rates of aspiration and pneumonia. Large well designed placebo-controlled RCTs are needed to assess the effectiveness of swallowing therapy for swallowing disorders in Parkinson's disease. The design of the trials should minimise bias and be reported fully using CONSORT guidelines. Outcome measures with particular relevance to patients should be chosen and the patients followed for at least 6 months to determine the duration of any improvement.
In this review, we examine the evidence from four randomized clinical trials involving 1477 people with ALS. The methodological quality of the trials was acceptable and three of the trials were easily comparable (although one of them included older patients with more advanced ALS). The searches for this review were last updated in 2011, when we found no new randomized controlled trials. The results indicate that riluzole 100 mg probably prolongs median survival in people with ALS by two to three months and the safety of the drug is not a major concern. The evidence from randomized controlled trials indicates that participants taking riluzole probably survive longer than participants taking placebo. The beneficial effects are very modest and the drug is expensive. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. Adverse effects from riluzole are relatively minor and for the most part reversible after stopping the drug.
We found 15 trials (1253 women) comparing G-CSF with placebo or no treatment. Eleven trials evaluated the role of G-CSF in women undergoing IVF, with a majority of trials including those women with two or more failed attempts. The remaining four trials investigated the role of G-CSF in women with thin endometrium undergoing IVF. The evidence is current to February 2019. We are uncertain whether giving G-CSF in women undergoing IVF improves chances of ongoing pregnancy or overall clinical pregnancy rates or reduces miscarriage rate compared to placebo or no treatment. For a typical clinic with 14% ongoing pregnancy rate, G-CSF administration would be expected to result in ongoing pregnancy rates between 12% and 35%. No study reported on multiple pregnancy rate. Only four trials reported adverse events as an outcome, and none of them reported any major adverse events following either G-CSF administration or placebo/no treatment. We are uncertain whether giving G-CSF improves ongoing pregnancy or reduces miscarriage rates in women undergoing IVF based on very low-quality evidence. The quality of the evidence was reduced because of risk of bias.
This review of four studies with 166 relevant participants, looked at whether participating in home-based therapy programmes, targeted at the upper limb, could improve performance in activities of daily living (ADL), functional movement of the upper limb, performance in extended ADL and arm motor impairment. In comparison with usual care, home-based upper limb programmes had no difference in effect on any of the outcomes. In comparison with an upper limb programme based in hospital, we found home-based upper limb programmes to be no more or no less effective for arm motor impairment outcomes. The evidence in this area is limited. Further research is needed to determine the effects of home-based therapy programmes.
Our evidence is current to October 2015. Overall five studies were included in our review but we used data from three trials with 5896 residents . In one trial the average age was 77 and 71% were female, in another this was 82 years and 70% were female, and in the last this was 86 years and 77% were female. One study was supported by the Greater Glasgow Health Board Care of the Elderly Unit, one by the Wellcome Trust and for one there was no statement. The method of randomisation used was at low risk in two trials and unclear in one. In all three studies allocation concealment and blinding were unclear. In two studies data could not be included from everyone who was recruited and this put their results at a high risk of bias. All three studies reported outcomes completely. However, in all three trials there was performance bias due to incomplete influenza vaccination of healthcare workers in the intervention arms. No studies reported on adverse events. Offering influenza vaccination to healthcare workers who care for those aged 60 or over in LTCIs may have little or no effect on laboratory-proven influenza (low quality evidence). HCW vaccination programmes probably have a small effect on lower respiratory tract infection (moderate quality evidence), but they may have little or no effect on admission to hospital (low quality evidence). It is unclear what effect vaccination programmes have on death due to lower respiratory tract illness (very low quality evidence) or all cause deaths (very low quality evidence). This review did not find information on other interventions used in conjunction with vaccination of healthcare workers (for example, hand-washing, face masks, early detection of laboratory-proven influenza, quarantine, avoiding new admissions, prompt antiviral use, asking healthcare workers with an influenza-like illness not to work). High quality randomised controlled trials testing combinations of these interventions are needed.
Amongst the 13 studies identified, there was a small amount of evidence to suggest that EMG-BFB had a beneficial effect when used with standard physiotherapy techniques. However EMG-BFB cannot currently be recommended as an effective routine treatment because other studies found no effect, and the positive trials were small.
The evidence is current to June 2017. We included 15 studies involving 71,422 participants living in countries with or without mandatory supplementation of foods with vitamins. These studies compared different regimens of B vitamins (cyanocobalamin (B12), folic acid (B9) and pyridoxine (B6)) with a control or any other comparison group. The studies were published between 2002 and 2015. We found no evidence that homocysteine-lowering interventions, in the form of supplements of vitamins B6, B9 or B12 given alone or in combination, at any dosage compared with placebo, or standard care, prevented heart attack or reduced death rates in participants at risk of, or living with cardiovascular disease. Homocysteine-lowering interventions combined with antihypertensive medication had uncertain effects on stroke, approximately 143 people would need to be treated for 5.4 years to prevent 1 stroke. Homocysteine-lowering interventions compared with placebo or any other comparison did not affect serious adverse events (cancer). The quality of evidence from these studies was generally high.
We searched the medical literature widely for randomised controlled trials that investigated the effects of progesterone in people with TBI up to 30 September 2016. Randomised controlled trials provide the most robust medical evidence. . We included five studies with a total of 2392 participants, and identified three ongoing studies. The studies all compared a group of participants who received progesterone within 24 hours of TBI against a group who received a pretend - or dummy - medicine (known as a placebo) that looked the same as the progesterone. The results of our review did not find evidence that, when compared to placebo, progesterone could reduce death and disability in people with TBI. There were too few data available on the other outcomes that we were interested in (pressure inside the skull (intracranial pressure), blood pressure, body temperature and adverse events (harms)), for us to be able to analyse these in detail. However, although the information available shows no evidence of a difference in effect between the progesterone and control groups for intracranial pressure, blood pressure or body temperature, one study showed an increased level of an adverse event called phlebitis (inflammation in the vein) in the progesterone group, possibly because the progestreone was given into the vein through an intravascular infusion ('drip'). We judged the quality of the evidence to be low for the data on risk of death, and moderate for the data on risk of disability. These judgements resulted from differences across studies, including different doses of progesterone and different time points for assessment of participants in the included studies. This means that we have limited confidence in the conclusions of this review.
In searches of medical databases up to 28 January 2019, we found 11 relevant trials; most were small (involving 665 infants in total) and had methodological weaknesses. Currently available evidence suggests that feeding preterm infants hydrolysed formula (rather than standard formula) during their initial hospital admission has no important benefits or harms. However, this finding is not yet conclusive, and larger trials of better quality are needed to provide evidence to help clinicians and families make informed choices about this issue. Data from these trials provide no strong or consistent evidence that feeding preterm infants hydrolysed formula rather than standard formula improved or worsened digestion or changed the risk of severe bowel problems.
The review authors searched the medical literature for studies up to March 2014. We searched for trials which compared middle ear infections in people randomly selected to receive zinc supplements or who did not receive supplements. We found 10 eligible studies, all conducted amongst young children. The total number of participants was 6820. Nine trials were conducted in low- and middle-income countries. Seven trials were conducted on healthy children. Participants included both males and females. The results of the trials provided no convincing evidence that zinc supplements reduce the occurrence of middle ear infections in healthy children. However, in one small study of severely malnourished children, those receiving zinc supplements had fewer middle ear infections. The only adverse effect was vomiting. The trial evidence included is generally of good quality, with a low risk of bias. All the included trials included otitis media only as a secondary outcome. Therefore, there was a potential to miss trials which were less publicised or less well indexed within the electronic databases.
Two authors searched the medical literature available until July 2012 and obtained the information from the identified trials. The use of two authors to identify studies and obtain information decreases the errors in obtaining the information. We identified and included eight trials covering 109 surgical trainees in this review. The trials compared virtual reality with no supplementary training or with box-trainer training (physical simulator using a camera to display the inside of the box and instruments). There were no trials that compared different forms of virtual reality training. All the trials were at high risk of bias (defects in study design that can lead to arriving at wrong conclusions with overestimation of benefits and underestimation of harms of virtual reality training or standard training). Operating time and operative performance were the only outcomes reported in the trials. The remaining outcomes such as death, complications, quality of life, and hospital stay after the operation were not reported in any of the trials. Overall virtual reality training appears to decrease the operating time (by about 10 minutes) and improve the operative performance of surgical trainees (difficult to quantify from the available reports) with limited laparoscopic experience when compared with no supplementary training or with box-trainer training. However, the impact of this decreased operating time and improvement in operative performance on patients or healthcare funders in terms of improved health or decreased costs is not known. Further well-designed trials are necessary, with less risk of arriving at wrong conclusions because of poor study design or because of chance. Such trials should assess the impact of virtual reality training on patients and healthcare funders.
One 26-week randomised controlled study (45 participants) was included in the review. Participants were aged between six and 43 years old. The study was carried out in several centres around the world. Participants either received an intravenous infusion of laronidase 0.58 mg/kg or a placebo ('dummy' infusion). Current evidence is limited because we only found one randomised clinical trial in the medical literature, which did not include very many participants. Compared with placebo, enzyme replacement therapy improved lung function, the individuals’ ability to walk, reduced the excretion of abnormal glycosaminoglycans (a type of carbohydrate molecule) in the urine and also reduced the stopping of breathing related to sleep. Adverse reactions in relation to the infusions occurred in both groups but all were mild and none required medical intervention or for the infusions to be stopped. Enzyme replacement therapy can be used before and around the time of stem cell transplant, which is now the gold standard treatment for Hurler syndrome in individuals diagnosed before the age of two and a half years. More studies are needed to look at the long-term effects of this treatment and also to see the effects on the quality of life of these individuals. We do not anticipate any further trials to be undertaken and therefore do not plan to update this review. The included study was small and of low quality.
All the trials identified compared different types of contraceptive implant. No trials were found that compared implants to other contraceptive methods. All the implants were highly effective methods of contraception in the selected women. The majority of women using contraceptive implants chose to continue with the method long term, over 80% of women were still using their implant at two years. Women in developed country studies were less likely to continue with these methods when compared to women in developing country studies. The most common reported side -effect was of irregular vaginal bleeding. Bleeding with all implants became less frequent with time. Removal was quicker for Implanon and Jadelle than for Norplant. Insertion problems were rare with any of the implants. Problems at removal were uncommon but were significantly more likely to occur in Norplant users than Implanon users.
We undertook a systematic review of trials that compared the effects of group pregnancy care versus conventional individual pregnancy care on psychosocial, physiological, labour and birth outcomes for women and their babies as well as on care provider satisfaction. Four randomised controlled trials (involving 2350 women) were included: two were undertaken in the USA, one in Sweden and one in Iran. We found no differences between women who received group pregnancy care and those given one-to-one care in terms of important pregnancy outcomes such as preterm birth, infant birthweight or death of the baby. Women who attended group pregnancy care were no more likely to initiate breastfeeding than those receiving standard care. In one trial, women who attended group pregnancy care rated their satisfaction as similar to women receiving individual care. Major differences between trials were noted. One trial targeted young women 14 to 25 years of age in a setting with many African American women who had limited financial resources. The main purpose was to reduce human immunodeficiency virus (HIV) risk behaviour and sexually transmitted infections. Another trial was mainly looking at family readiness in a military setting, and another focused on women's satisfaction and emotional aspects of their care. This review is limited owing to the small numbers of studies and women, with one study contributing 42% of the women. More research is required to determine whether group pregnancy care is associated with significant benefits.
This review asks whether folic acid helps improve symptoms in people with fragile X syndrome and whether it has any side effects. We found five randomised controlled trials, all of which were published between 1986 and 1992. These studies included 69 people, all male. One of the studies compared a folic acid group with a control group; the other four used a cross-over design (i.e. participants received first one treatment and then the other). The quality of reporting of the trials was generally poor, particularly the methods used, which made it difficult to assess the risk of bias in the studies. The results of the few published studies did not find significant differences in the effects of folic acid or placebo on psychological or learning capabilities, behaviour or social performance, as measured by standardised tools. There is therefore no evidence to support the recommendation of supplementing dietary intake with folic acid medication for people with fragile X syndrome. However, due to the number and quality of the studies, it is not possible to conclude with any certainty that folic acid does not help. Given that intellectual, behavioural, emotional and/or learning performance in people with fragile X syndrome are strongly influenced by different social factors, future studies should also pay attention to the evaluation of non-pharmacological interventions, such as modifications in the home environment, tailored behavioural interventions and classroom environments, or language and occupational therapy.
This is an update of the original review published in 2013. We found one new study in a search of the published literature in February 2015. This review includes 24 studies with 2996 participants. We compared different types of bed rest and extra fluids to see if they prevented PDPH after a lumbar puncture. We found low to moderate quality evidence that bed rest does not prevent the onset of headaches after lumbar puncture, regardless of the duration of rest or the body or head positions assumed by the patient. Furthermore, bed rest probably increases the chances of having PDPH. We found few data on the usefulness of extra fluids, which did not seem to prevent PDPH. We believe that these practices should no longer be routinely recommended to patients for the prevention of headaches after lumbar puncture since there is no evidence supporting them. We considered the quality of the evidence for most of the outcomes assessed in this review to be low to moderate.
We searched a wide range of medical databases on 7 February 2018. We identified 2398 potential studies, 30 of which we looked at in detail. We found one suitable study, however although the study is complete the manuscript has not yet been accepted for publication, and so we were unable to analyse the data. We have assigned the study as awaiting classification; once its results are published we will evaluate it again and decide if it is eligible for inclusion in the review. We found one registered trial that is investigating our review question, but it is still ongoing and not yet completed or published. We failed to locate any published randomized controlled trials (RCTs) to support or refute the assertion that vascular access specialist teams are superior to the generalist model for device insertion and prevention of failure. However, this conclusion may change once the one study awaiting classification and the one ongoing study are published. There is a need for good-quality RCTs to evaluate the efficacy of a VAST approach for VAD insertion and prevention of failure. An RCT is a study (or trial) that aims to reduce bias when testing a new treatment. The people taking part in the trial are randomly allocated to either the group receiving the treatment under investigation or to a group receiving standard treatment (or placebo treatment) as the control. We did not analyse the quality of the evidence as we did not find any suitable studies to include in our review.
The review included trials comparing agomelatine with a group of antidepressants called selective serotonin reuptake inhibitors (SSRIs), and one antidepressant from the serotonin–norepinephrine reuptake inhibitor group, called venlafaxine. Participants in the studies were followed up for between six to 12 weeks. - Agomelatine was no more or less effective in reducing symptoms of depression than any of the other antidepressants. - Agomelatine was no more or less effective in preventing relapse of depression than any of the other antidepressants. - Agomelatine was tolerated better than venlafaxine (fewer people discontinued treatment), but the same as the SSRIs. - Agomelatine caused a lower rate of dizziness than venlafaxine. - Agomelatine caused a lower rate of vomiting, nausea and sexual side-effects than SSRIs. The reviewers conclude that agomelatine is not more effective than other antidepressants currently on the market. It did seem to be more tolerable to patients in terms of lower rates of some side-effects, however, the quality of trials was low and there were only a few trials that compared agomelatine with each medication. No firm conclusion on agomelatine can be made because of problems with reporting of data in the trials included. The authors recommend that further trials of agomelatine versus placebo (dummy pill), particularly in primary care settings (where the majority of patient/practitioner contact take place, e.g. GP surgeries), should be carried out to improve the quality of evidence.
For the present review, researchers in The Cochrane Collaboration reviewed the evidence about the effects of valproate (valproic acid or sodium valproate or a combination of the two) in adult patients (≥ 16 years of age) with 'episodic' migraine (headache on < 15 days per month). They examined research published up to 15 January 2013 and found 10 relevant studies. Compared with placebo, valproate reduced the frequency of migraine headaches by approximately four per month (two studies, 63 participants). Patients were also more than twice as likely to reduce the number of their migraine headaches by 50% or more with valproate than with placebo (five studies, 576 participants). Side effects associated with valproate were common but generally mild; valproate can, however, cause birth defects and so should be used with caution in women of childbearing age. Further research is needed comparing valproate with other active drugs used for preventing migraine attacks.
In July 2014 we performed searches to look for clinical trials where topical lidocaine was used to treat neuropathic pain. We found 12 small studies of modest quality that tested topical lidocaine against topical placebo for a number of weeks. One study also tested a cream containing amitriptyline, which is an antidepressant. The 508 people in the studies had different types of neuropathic pain, with pain after herpes zoster infection the most common. There was some indication that topical lidocaine was beneficial in these studies (very low quality evidence). There was no clear evidence of an effect of lidocaine on the incidence of adverse events or withdrawals (very low quality evidence). A number of studies of topical lidocaine in neuropathic pain are ongoing. Several are large and of long duration. They will be of great help in working out the benefits of topical lidocaine when they are completed and results can be incorporated in this review.
When all the identified trials were combined, hepatitis B vaccine alone, hepatitis B immunoglobulin alone, and hepatitis B vaccine plus hepatitis B immunoglobulin reduced perinatal transmission of hepatitis B compared with placebo or no intervention. Hepatitis B vaccine plus hepatitis B immunoglobulin were superior to hepatitis B vaccination alone. Adverse events were rare and mostly non-serious.
This review investigated whether the administration of glucocorticoids around the time of implantation improved clinical outcomes in women undergoing IVF or ICSI when compared to no glucocorticoid administration. The review of trials found no evidence that glucocorticoids helped to improve live birth rates. However, there was some evidence of increased pregnancy rates, rather than live birth rates, among women undergoing IVF. This was not found in women undergoing ICSI. More research is needed to elucidate the possible role of this therapy in well defined patient groups.
This review considered all evidence provided by studies that assess the diagnostic accuracy of total serum bile acids (TSBA) and any component of serum bile acid profile for intrahepatic cholestasis of pregnancy in woman claiming onset of pruritus during pregnancy. We assessed all available reports from a wide, systematic search of databases of medical literature, irrespective of design, publication status, language, and study design. We finally included 16 studies, most of them assessing the accuracy (sensitivity and specificity) of TSBA with a cut-off of 10 μmol/L. Most studies had a case-control design, and these studies could have overestimated the diagnostic accuracy. When considering the studies with a cut-off of 10 μmol/L for TSBA serum concentration, TSBA overall sensitivity (the ability to correctly identify women with the disease) ranged from 72% to 98% and specificity (the ability to correctly identify women without the disease) ranged from 81% to 97%. However, after performing two different analyses excluding studies with probably less reliable results, the diagnostic accuracy seemed lower. We calculated the overall accuracy also of some components of serum bile acid profile, but the small number of studies and the high variability of the results led to very imprecise data. Only one of the 16 included studies was performed and reported well (low risk of bias). The remaining 15 studies had problems with study design or reporting (high risk of bias). Only five studies seemed to show low concern regarding applicability of the results in clinical practice. The overall high risk of bias, the existing concern regarding applicability of the results in clinical practice, and the poor uniformity of our results in the included studies prevents us from making recommendations and reaching definitive conclusions at present. Thus, we do not find any compelling evidence to recommend or refute the routine use of any of these tests in clinical practice. So far, the diagnostic accuracy of TSBA for intrahepatic cholestasis of pregnancy might have been overestimated. There were too few studies to permit a precise estimate of the accuracy of serum bile acid profile components. Further primary clinical research is mandatory. We need both further phase II and phase III diagnostic studies.
We found two eligible studies reporting on 18 methodological filters, including six MEDLINE, six Embase and six combined MEDLINE/Embase filters. The firsts study focused on filters on observational studies of surgical interventions. The second study focused on filters for a specific subtype of observational studies: comparative non-randomised studies. Six filters from the first study showed sensitivity of 99.5% to 100% and precision of 16.7% to 21.1%. One type of filter was evaluated by two additional systematic reviews (i.e. externally validated) and found that this retrieved 85.2% to 100% of the articles in the reference standard. Twelve filters from the second study had lower sensitivity (48% to 100%) and much lower precision (0.09% to 4.47%). The included studies had several limitations. The first study used only one systematic review for search strategy development and focused on observational studies of surgical interventions, which might limit the generalizability of the findings to other literature searches. The reference standard in the second study, although encompassing four different systematic reviews, included a limited number of studies, which might affect the accuracy of the performance assessment. Both studies were published 10 years ago and labelling and indexing of observational studies has changed since then.
The main purpose of this systematic review was to determine the effectiveness of multidisciplinary rehabilitation for fibromyalgia and wide spread musculoskeletal pain among working age adults. Patients included in the controlled trials in this review ranged in age from 18-65 years. Seven studies, with 1050 patients were included. The effectiveness of multidisciplinary rehabilitation was graded limited, showing no quantifiable benefit for both fibromyalgia and widespread musculoskeletal pain.
We identified all randomized controlled trials in ALS/MND and wrote to the authors to request the data needed to complete this review. Although many more studies were eligible for inclusion, only five authors were willing and able to share the data from their individual randomized controlled trials. Based on the analyses of these data, we find no evidence to support a statistically significant difference in the response to treatment between people with the familial and sporadic forms of ALS/MND.
We included four randomised controlled trials involving 543 women. The studies took place in the United Kingdom, Turkey, Egypt and Hong Kong, and the primary outcome in all studies was abnormal changes in the lining of the uterus. Three studies reported on the outcome of fibroids. Three studies reported on abnormal vaginal bleeding or spotting. Two studies reported on the outcomes of breast cancer recurrence, and three studies reported on the outcomes of breast cancer-related death. The evidence is current to October 2015. This review suggests that the LNG-IUS can reduce the risk of endometrial polyps and endometrial hyperplasia over a long-term follow-up period (24 to 60 months) in women taking tamoxifen following breast cancer. At 12 and 24 months of follow-up, more women in the LNG-IUS group experienced abnormal vaginal bleeding or spotting. However by 60 months of follow-up, no abnormal vaginal bleeding or spotting was reported in either group. There were insufficient data to show whether there is any effect on incidence of endometrial cancer (a cancer originating in glandular tissue), fibroids, breast cancer recurrence, or breast cancer-related death. The quality of the evidence was judged as moderate, due to limited sample sizes and low event rates for the outcome comparisons. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and the impact of the LNG-IUS on the risk of secondary breast cancer events.
We searched medical databases and found two types of studies that addressed our review question. One group of five trials studied communities in which sick newborns were offered antibiotics in the home or ambulatory clinics and compared them to communities in which sick newborns received only the standard referral to a hospital. The second group of five trials treated sick newborns in the home or clinic with either the intravenous antibiotics that are typically administered in the hospital or with simpler antibiotic regimens that relied more on oral antibiotics. The trials were conducted in a variety of countries within sub-Saharan Africa and South Asia. The evidence is up to date as of 16 April 2018. There is reduced risk of newborn death when sick newborns are given antibiotics in the home or clinic compared to sick newborns who are only referred to a hospital, but this result is based on low-quality evidence. In addition, the majority of the studies that examined home- or clinic-based antibiotics included other interventions, such as improved care at birth, that may have influenced the findings. Moderate-quality evidence showed that antibiotic regimens that involve fewer injections and can be administered in the home or clinic do not result in more newborn deaths when compared to the typically administered antibiotic regimens that rely solely on injections. Based on this result, simpler antibiotic regimens delivered in the home or clinic may be considered as an alternative treatment for sick newborns that cannot access a hospital. However, it is important to remember that the studies were conducted under ideal conditions with a high level of patient monitoring. Additional research in real-world settings with limited resources are recommended to determine if the results hold true. The quality of evidence ranged from low to moderate quality.
We searched the scientific literature for all randomised controlled trials (RCTs) and quasi-RCTs published up to July 2015. RCTs are studies in which people are randomly allocated to treatment groups. Quasi-RCTs are studies in which people receive treatment based on methods that are not strictly random such as date of birth, or their hospital record number, and the results of quasi-RCTs are generally considered less trustworthy than those of RCTs. We found 24 trials (22 RCTs and two quasi-RCTs) to include in our review. These studies included, in total, information from 3161 parents and their young children. Eight studies had been carried out in the USA, five in the UK, four in Canada, five in Australia, one in Mexico, and one in Peru. All of the studies looked at behavioural, cognitive-behavioural or videotape modelling parenting programmes. Behavioural programmes are aimed at helping parents develop methods that will reduce bad behaviour, usually with the use of techniques such as praise or rewards. It also aims to help parents set limits that make sense. Cognitive-behavioral skills allow parents think about behaviour patterns and focus on solutions. Programmes can use a variety of techniques; for example, videotape modelling programmes enable parents to learn by watching videotaped films of other parents implementing some of the techniques described above. Some of the studies we found included people chosen specially because they were ‘at risk’ of behavioural problems, while others included parents and children without any specific risks. When we put all of the studies together, overall, we found that group-based parenting programmes can improve the emotional and behavioural development of young children, although the quality of the evidence was, on the whole, low. Furthermore, our findings were not convincing when we removed two studies that used quasi-randomised methods. Our findings also showed evidence of an improvement in externalising problems (these might include negative behaviours in children or young people that are directed towards the external environment such as anger, aggression or conflict with the law). However, the evidence for this, once again, came from studies that we rated as being of only moderate quality, and was only found for some parts of the outcome measure (known as a subscale). Results from single studies that could not be combined with other studies and that were of poor quality, on the whole, showed no impact on children’s internalising problems (e.g. depression and anxiety). However, there was some improvement on one subscale of a measure that focused on children’s hyperactivity-inattention and another subscale that focused on social skills. There was moderate-quality evidence that group-based parenting programmes also improve the way in which parents and children interact, as measured by fewer negative behaviours. Our reasons for rating the quality of the evidence as low or moderate included: inconsistency in the findings from different studies (different studies yielded different results); unclear risk of bias (where it was not possible for us to assess the ways in which the included studies might be biased due to inadequate information); and small numbers of parents in the included studies. We believe more research is needed to be able to reach a firm conclusion about whether the effects we have found are short term only or whether they continue over time and therefore may be able to prevent future behavioural problems.
Small asymptomatic AAAs are at low risk of rupture and are monitored through regular imaging so they can be surgically repaired if they subsequently enlarge. This review identified four well-conducted, controlled trials that randomised 3314 participants with small (diameter 4.0 cm to 5.5 cm) asymptomatic AAAs to immediate repair or regular, routine ultrasounds to check for aneurysm growth (surveillance). Among the patients randomised to surveillance, the aneurysm was repaired if it was enlarging, reached 5.5 cm in diameter, or became symptomatic. The four trials showed an early survival benefit in the surveillance group because of the number of deaths within 30 days of surgery (operative mortality). The trials did not show a meaningful difference in long-term survival between immediate repair and selective surveillance over the three to eight years of follow-up. Some 31% to 75% of the participants randomised to surveillance eventually had the aneurysm repaired. Overall, the risk of bias within the included studies was low and the quality of the evidence high. The results from the four trials conducted to date suggest no overall advantage to immediate surgery for small AAAs (4.0 cm to 5.5 cm). A pooled analysis of the two trials comparing immediate open surgical repair to surveillance demonstrated that this result holds true regardless of patient age or aneurysm size (within the range of 4.0 cm to 5.5 cm diameter). Furthermore, the more recent trials, which focused on the efficacy of endovascular repair, also failed to show a benefit over surveillance. Quality-of-life results among trials were conflicting. Thus, neither immediate open nor immediate endovascular repair of small AAAs is supported by the current evidence.
Four studies including 9130 adults and adolescents were included. None of the studies included children younger than age 12. The studies lasted for six months to a year, and all were funded by one drug company. Studies included more women than men, with average age of about 40. Three studies recruited people with quite similar symptoms, but one study included people with less severe asthma. The studies were well conducted, although two did not hide which treatments were being taken (known as blinding), which might have affected the results. The amount of inhaled steroids, including puffs taken for relief from symptoms, was consistently lower for SiT than for the comparison groups using two types of inhalers. Overall, we believe that the quality of the evidence was high to moderate. Fewer people taking SiT had flare-ups that needed a hospital stay or a visit to the ER (one fewer per 100 treated than in the control group, 95% CI 0 to 2 fewer) or a course of oral steroids (two fewer per 100 treated, 95% CI one to three fewer). If more studies are published, it is unlikely that our opinions on these main findings will change. However, we could not tell whether one treatment caused more serious adverse events than the other. SiT had a small benefit on one measure of lung function (predose forced expiratory volume in one second (FEV1)). However, for several other measures, not enough information was available to show which treatment was better (amount of medication taken on an 'as needed' basis, various symptom measures and quality of life). In conclusion, SiT reduces the need for a hospital stay or an ER visit and for courses of oral steroids for asthma flare-ups. SiT did not increase the quantity of inhaled steroids taken overall, and it was unclear whether it increases or decreases serious side effects. Currently no data are available for the use of SiT in children younger than age 12.
Our analyses of 40 studies of people with chronic kidney disease shows that people referred earlier to a specialist kidney doctor lived longer. Death rates in people referred early were about half of those referred late and these benefits were seen as early as three months and lasted for at least five years. People referred early also spent less time in hospital and were better prepared for dialysis. Dialysis first requires surgical placement of a fistula and early referral to specialist services often means better preparation, a lower risk of infection and other complications. We did not discover any adverse effects from early specialist referral. Randomised controlled trials provide the most reliable information of all study designs, so it should be noted that all 40 studies analysed for this review used a cohort design. Cohort studies are the next best level of evidence and the only available evidence. For ethical reasons it is unlikely that a randomised controlled trial that deliberately assigns patients to late specialist referral will ever be conducted.
This review examined trials which compared antidepressants with 'active' placebos, that is placebos containing active substances which mimic side effects of antidepressants. Small differences were found in favour of antidepressants in terms of improvements in mood. This suggests that the effects of antidepressants may generally be overestimated and their placebo effects may be underestimated.
Children in all the trials experienced a rapid, short-term reduction in pain after using ear drops. It is hard to know if this was the result of the natural course of the illness; the placebo effect of receiving treatment; the soothing effect of any liquid in the ear or the pharmacological effects of the ear drops themselves. Nevertheless, there is some evidence that when combined with oral pain medication, anaesthetic ear drops may help to relieve pain more rapidly in children aged three to 18 years. More good-quality trials are needed.
Authors for the Cochrane Oral Health Group carried out this review of existing studies. The evidence on which it is based is current up to 26 November 2014. We included two studies involving a total of 111 participants in this review. A single orthodontic specialist in a private practice in Australia carried out one study, while the other study was conducted on patients treated by orthodontic residents in a university hospital seating in the United States of America. In one study, the age of participants ranged from 11 to 15 years old, and in the second, the average age of participants was 21 years. The studies evaluated the additional use of two devices that use light vibrational forces - Tooth Masseuse in people receiving conventional fixed appliance treatment during the tooth alignment stage and OrthoAccel for those receiving conventional fixed appliance treatment for the space closure stage in orthodontic treatment. Participants receiving additional treatment with the devices were compared to those receiving only the conventional treatment. The trials evaluated different aspects of orthodontic tooth movement and side effects. The studies evaluated three outcomes: rate of tooth movement; patient perception of pain and discomfort, and unwanted side effects. There were substantial differences between the studies, which meant that we were unable to combine the results. From the limited evidence available, it is not possible to establish if the use of vibrational forces during treatment with fixed orthodontic appliances has a significant beneficial or harmful effect on either the rate of orthodontic tooth movement or the duration of treatment. The quality of evidence was very low.
We first searched the literature in 2004 and most recently in September 2014, finding 6 studies in total. All studies included patients with heart attack and some also included patients with severe angina. The dose of hyperbaric oxygen was similar in most studies. Overall, we found some evidence that people with ACS are less likely to die or to have major adverse events, and to have more rapid relief from their pain if they receive hyperbaric oxygen therapy as part of their treatment. However, our conclusions are based on relatively small randomised trials. Our confidence in these findings is further reduced because in most of these studies both the patients and researchers were aware of who was receiving HBOT and it is possible a 'placebo effect' has biased the result in favour of HBOT. HBOT was generally well-tolerated. Some patients complained of claustrophobia when treated in small (single person) chambers and there was no evidence of important toxicity from oxygen breathing in any subject. One individual suffered damage to the eardrum from pressurisation. While HBOT may reduce the risk of dying, time to pain relief and the chance of adverse heart events in people with heart attack and unstable angina, more work is needed to be sure that HBOT should be recommended.
This review identified 77 studies with over 5,000 people who received various treatments. The population in these trials was mainly aged between 50 and 70 years. Trial quality was generally poor; particular problems included small study size, and not reporting adverse events in all patients, or all recorded adverse events. Known problems with adverse event measurement, recording, and reporting made assessment even more difficult. For all four opioids together, 1 in 4 people experienced constipation and somnolence (sleepiness, drowsiness), 1 in 5 experienced nausea and dry mouth, and 1 in 8 experienced vomiting, loss of appetite, and dizziness. Weakness, diarrhoea, insomnia (difficulty in sleeping), mood change, hallucinations and dehydration occurred at rates of 1 in 20 people and below. These results may contribute to understanding the effects of opioids on consciousness, appetite, and thirst in end-of-life care in all patients deemed to be people who are dying.
Women requiring extensive surgery (urinary and or feacal stoma formation) or with inoperable tumour were predominantly given primary chemoradiation in the two retrospective studies identified, making the available evidence weak (although we only included studies that used statistical adjustment). There was no data on quality of life. There is a great need for good quality studies comparing various primary treatments in locally advanced vulval cancer which are either inoperable at presentation or operable but would require extensive surgery.
From available evidence until December 2012, we found 16 trials involving 6872 adults and two trials involving 336 children contributing to the review. The risk of asthma exacerbations requiring the use of corticosteroids was lower with the combination of LABA + ICS compared with LTRA + ICS—from 13% to 11%. The choice of LTRA (montelukast or zafirlukast), the dose of ICS and the age of patients did not significantly affect the results. The effect appeared stronger in trials of short duration and in those using a single device to administer both ICS and LABA. Serious adverse events were more common with LABA than with LTRA, particularly in adults. The combination of LABA + ICS was superior to LTRA + ICS in terms of lung function and was modestly superior in other indicators of the control of asthma and quality of life. LTRA was found superior in preventing deterioration during exercise. The risk of withdrawal from a trial for any reason was significantly lower with LABA than with LTRA. More patients were satisfied with the combination of LABA + ICS, and fewer changed therapy if they started with LABA instead of LTRA. In adults whose asthma is inadequately controlled with ICS, the addition of LABA to ICS was found to be modestly superior to LTRA + ICS. Although both options appeared safe, evidence suggests that slightly more serious adverse events (SAE) may be seen with LABA than with LTRA, particularly when separate devices are used to administer LABA + ICS. Because only two paediatric trials contributed data to the review, the best adjunct strategy to ICS remains uncertain for children. Our confidence in the quality of evidence is high in the primary efficacy outcome (i.e. patients with exacerbation requiring systemic corticosteroids and high to moderate efficacy and safety measures). One open-label study of adult patients with asthma contributed to certain outcomes that led to downgrading of the quality of evidence from high to moderate. Of note, only two paediatric trials contributed to this review.
We found one published randomised controlled trial with 2001 participants with localised skin cancer who had undergone removal of the primary tumour and were then randomised to receive SLNB or observation. Participants testing positive for cancer cells in the sentinel lymph node then underwent CLND. Participants in the observation group underwent removal of the lymph nodes only on disease recurrence. The study did not report on our primary outcome of interest (overall survival), but it did report on our secondary outcomes of disease-specific survival (time to death only from melanoma), disease-free survival (time to first melanoma recurrence at any site), and recurrence. Although the authors of the one included study did not report the primary outcome of overall survival, we were able to calculate it from data they included in their report appendix which showed no benefit of SLNB for people with intermediate or thick melanomas. Our one included study also did not report any difference in disease-specific survival for participants who underwent SLNB or observation. Disease-free survival was better in the SLNB treatment group. However, recurrence of the melanoma at a distant site in the body occurred more frequently in participants in the SLNB group than in those in the observation group. We assessed the quality of the evidence for this trial as low for the above outcomes. As indicated by the results of this one included study, there is no clear evidence at present to recommend that SLNB, followed by CLND. is a better means of improving overall or melanoma-specific survival than observation.
Eighteen trials randomised 3888 people to rosiglitazone therapy. The longest duration of rosiglitazone treatment was four years, most trials lasted around half a year. Unfortunately, the published studies of at least 24 weeks rosiglitazone treatment in people with type 2 diabetes mellitus did not provide relevant evidence that patient-oriented outcomes are positively influenced by this agent. The chance of developing oedema was approximately doubled, the risk of cardiovascular diseases increased. The single large randomised controlled trial showed evidence of raised cardiovascular risk after rosiglitazone treatment. Moreover, new safety data show increased numbers of broken bones in women. This finding was published years after approval of this agent by drug regulatory authorities. New ways of exploring drug effects, for example by early long-term studies in many people, as well as public access to all safety data of published and unpublished investigations have to be established.
It is used in pregnancy to study blood circulation in the baby, the mother's uterus and the placenta. If abnormal blood circulation is identified, then it is possible that medical interventions might improve outcomes. We set out to assess the value of using Doppler ultrasound of the mother's uterus or placenta (utero-placental Doppler ultrasound) as a screening tool. Other reviews have looked at the use of Doppler ultrasound on the babies' vessels (fetal and umbilical Doppler ultrasound). We also choose to look at women with low-risk and high-risk pregnancies, and in their first or second trimesters. This screening offers a potential for benefit, but also a possibility of unnecessary interventions and adverse effects. The review of randomised controlled trials of routine Doppler ultrasound of the uterus or placenta identified two studies involving 4993 women. All the women were in the second trimester of pregnancy and at low risk for hypertensive disorders. The studies were of good quality but small in size. We identified no improvements for the baby or the mother. However, more data would be needed to show whether maternal Doppler is effective, or not, for improving outcomes. We did not find any studies in the first trimester of pregnancy or in women at risk of high blood pressure disorders. More research is needed on this important aspect of care.
In 11 of the studies, pharmacists gave education and counselling to patients with chronic illnesses such as asthma and diabetes. Pharmacists gave the patients information about how to use their medicines properly and about possible side effects of the medicines, and helped them to identify and solve problems with their medicines. They also gave the patients information about the disease and advice about self-management and the importance of a healthy lifestyle. The patients who were given these services were compared to patients who were given the usual pharmacist services without education or counselling. In one study, pharmacists gave education to general practitioners (GPs) about care of children with asthma. These GPs were compared to GPs who were given usual pharmacist services. No studies were found where pharmacist-provided services were compared to the services provided by other health workers. What happens when pharmacists provide services other than dispensing medication? When pharmacists give education and counselling to patients with chronic illnesses: · patients may experience small improvements in health outcomes such as blood pressure levels and glucose levels (low quality evidence), · patients may use health services less (for instance fewer visits to the doctor, fewer stays in hospital) (low quality evidence), · patients probably experience small improvements in quality of life (moderate quality evidence), · patients’ medication costs may be lower (low quality evidence). When pharmacists give education and counselling about asthma care to GPs: · their patients may experience slightly fewer asthma symptoms (low quality evidence).
This systematic review examined studies from 1980-2009 that identified both provider experience/qualifications as well as a volumes indicator (number of HIV/AIDS patients). Only four studies met the inclusion criteria for the final review. Given the varied methods of each study, a meta-analysis was not possible.
In March 2016, we searched five medical databases. We found one clinical trial that was eligible for inclusion; the trial investigated the medicine modafinil in 37 adults with PBT and high levels of fatigue. People in the study received six weeks of modafinil followed by a one-week washout period and six further weeks of placebo, or vice versa. The washout period aims to allow time for any effects of the first treatment to wear off before the new one gets started. The one included trial found no evidence of a difference between modafinil and placebo in treating fatigue. It is possible that this could be due to the trial not reaching its planned number of participants. Several other studies investigated the management of fatigue too, but in these studies high fatigue was not essential for participation. We do not currently know whether any treatments are effective in the management of people with PBT and high fatigue. With only one included trial, the overall quality of evidence was low. More high-quality studies are needed that enrol adults with BPT and high fatigue.
This review, carried out within the Cochrane Oral Health Group, is an update of one we published in 2008 and the evidence is current up to March 2015. We identified another five relevant studies for inclusion in this review and therefore this review includes 12 studies, which involved 389 participants. There is one Chinese study awaiting classification. Participants in the included studies were aged between 27 and 78 years, and there were roughly the same number of men and women involved. The studies we included had to be randomised controlled trials with at least three months of follow-up that evaluated full-mouth scaling and root planing within 24 hours. Both FMS and FMD were compared to conventional quadrant scaling and root planing, which was the control group. Participants had to have a clinical diagnosis of chronic periodontitis according to the International Classification of Periodontal Diseases. We excluded studies of people with aggressive periodontitis, systemic disorders or who were taking antibiotics. Treatment effects of FMS and FMD compared to conventional scaling and root planing (SRP) are modest and there are no clear implications for periodontal care. Harms and adverse events were reported in eight studies. The most important harm identified was an increased body temperature after FMS or FMD treatments. In practice, the decision to select one approach to non-surgical periodontal therapy over another can include patient preference and the convenience of the treatment schedule. The quality of the evidence is low for all treatment comparisons and outcomes. This is due to the small number of studies and participants involved and limitations in the study designs. Future research is likely to change findings.
We included 56 studies enrolling 2838 participants. Antihypertensive agents were the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined here were predominantly angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or combinations of both, compared with other antihypertensives and other agents. The benefits of antihypertensive agents appear to potentially outweigh the harms in patients with IgAN. The benefits were mostly reported as a reduction in 24 hour proteinuria. There is no evidence that treatment with any of the antihypertensive agents evaluated to date affect major renal and/or cardiovascular endpoints or long-term mortality risk beyond the benefit that arises from controlling hypertension in patients with IgAN. The RCT evidence is insufficiently robust to demonstrate efficacy for any of the other non-immunosuppressive therapies evaluated here. IgAN remains a disease in search of adequately powered RCTs to reliably inform clinical practice. More and better evidence is needed to understand the magnitude of benefit and the possible risks of anti-hypertensive or more specifically of ACEi/ARB therapy alone or in combination and which specific types of patients with the IgAN might have the greatest potential for benefit. For other non-immunosuppressive therapies, where benefit nor significant harm has yet to be demonstrated, there remains some justification for further exploration of the potential benefits.
We searched electronic databases and other resources for studies of PLD for relapsed ovarian cancerEOC, and included 14 studies up to October 2012. Most of these studies (12/14) were funded by drug manufacturers with a commercial interest in PLD (two studies) or the comparator drugs (10 studies). For women with platinum-sensitive relapsed EOC, we pooled data from two studies (1164 participants) that compared carboplatin plus PLD (PLD/carbo) with standard treatment (paclitaxel plus carbo (PAC/carbo)). Women survived for a similar length of time overall on these two treatments but the cancer took longer to progress in those receiving PLD/carbo. Women who received PLD experienced more severe low blood cell counts than the standard treatment. By comparison, women in the standard treatment group experienced more severe hair loss, nerve damage, allergic reactions, and joint and muscle pain. More women in the standard treatment group stopped treatment early suggesting that PLD/carbo was better tolerated than standard treatment. We concluded that PLD/carbo was a better treatment option than PAC/carbo for platinum-sensitive relapsed EOC. Five studies compared PLD to five other chemotherapy drugs. The numbers of participants in these studies ranged from 97 to 829 women and we did not pool these data. PLD worked as least as well as the other agents and was comparatively well-tolerated. In all studies, hand-foot syndrome (HFS: swollen, painful, red, cracked and peeled soles and palms) occurred more frequently in the PLD group. Three studies compared PLD plus another drug (canfosfamide (CAN), vintafolide (EC145) or trabectedin (TBD)) to PLD alone. The final results of the CAN study were not reported. The numbers of participants in the other studies ranged from 149 to 672 women and we did not pool these data. Women receiving the PLD/TBD combination treatment progressed six weeks later than those getting PLD only, however they did not live longer overall, and the combination treatment was associated with additional harmful effects. EC145 may improve survival in women with platinum-resistant relapsed ovarian cancer when combined with PLD; this combination is currently under investigation in a large trial. Although HFS can be severely disabling, we noted that it occurred much less frequently when lower doses of PLD were used. We consider the evidence related to the longer time to cancer progression with PLD/carbo for platinum-sensitive relapsed ovarian cancer to be of a high quality. There is currently insufficient evidence to support the use of other PLD combination treatments in relapsed EOC.
An electronic search of Cochrane Schizophrenia's register of studies was carried out in 2013. Review authors looked for trials that randomised people with schizophrenia to receive either oral fluphenazine or an atypical antipsychotic. Four studies with a total of 202 people with schizophrenia could be included. The trials compared fluphenazine with either amisulpride, risperidone, quetiapine or olanzapine. Results  Data showed oral fluphenazine is no better or worse in improving mental state than amisulpride but more people receiving oral fluphenazine did need to take additional anticholinergic medication (drugs used to help relieve a range of symptoms such as involuntary movements of the muscles, high blood pressure and insomnia). Data from the trials comparing oral fluphenazine with either risperidone, quetiapine or olanzapine also showed no superiority between the treatment groups for clinical improvement. Only the trial comparing oral fluphenazine with olanzapine provided adverse-effects data. Again, incidence of akathisia, a movement disorder, was similar between treatment groups. Quality of evidence  Evidence from these few trials is poor, of low quality and involves a small number of participants. It does not provide clear overall information about whether oral fluphenazine is better or worse than atypical antipsychotic drugs for treating people with schizophrenia. Data were not available for important outcomes such as such, relapse, hospital admission, satisfaction, costs and quality of life. Adverse-effects data were poorly reported. Future large-scale research should report on these important outcomes. Conclusions  Fluphenazine is low cost and widely available, so is likely to remain one of the most widely used treatments for schizophrenia worldwide. However, evidence currently available from randomised controlled trials about its effectiveness compared to atypical antipsychotics is unclear.
We included 38 randomised studies published up to October 2013. Trials tested a variety of different interventions and controls. The specific points used, the number of sessions and whether there was continuous stimulation varied. Three studies (393 people) compared acupuncture to a waiting list control. Nineteen studies (1,588 people) compared active acupuncture to sham acupuncture, but only 11 of these studies included long-term follow-up of six months or more. Three studies (253 people) compared acupressure to sham acupressure but none had long-term follow-up. Two trials used laser stimulation and six (634 people) used electrostimulation. The overall quality of the evidence was moderate. Key findings Three studies comparing acupuncture to a waiting list control and reporting long-term abstinence did not show clear evidence of benefit. For acupuncture compared with sham acupuncture, there was weak evidence of a small short-term benefit but not of any long-term benefit. Acupuncture was less effective than nicotine replacement therapy (NRT) and not shown to be better than counselling. There was limited evidence that acupressure is superior to sham acupressure in the short term but no evidence about long-term effects. In an analysis of the subgroup of trials where the treatment included continuous stimulation, those trials which used continuous acupressure to points on the ear had the largest short-term effect. The evidence from two trials using laser stimulation was inconsistent. The seven trials of electrostimulation do not suggest evidence of benefit compared to sham electrostimulation. The review did not find consistent evidence that active acupuncture or related techniques increased the number of people who could successfully quit smoking. However, some techniques may be better than doing nothing, at least in the short term, and there is not enough evidence to dismiss the possibility that they might have an effect greater than placebo. They are likely to be less effective than current evidence-based interventions. They are safe when correctly applied.
Randomised controlled trials (RCTs) use the play of chance to allocate participants to comparison groups to prevent selection bias. Other means of treatment allocation are more prone to bias because decisions about which treatment to use can be influenced by the preferences of the physician or patient. This review compares random allocation (allocated to treatment using a random method) versus non-random allocation (allocated to treatment using a non-random method, such as alternation or external, uncontrollable factors, with no clinical judgement involved) and controlled trials with adequate versus inadequate/unclear concealment of allocation. Concealed treatment allocation is best described in general terms as the process used to prevent foreknowledge of group assignment in a controlled trial (such as the use of sequentially numbered opaque, sealed envelopes). The results of randomised and non-randomised studies sometimes differed. Sometimes non-randomised studies yielded larger estimates of effect, and sometimes randomised trials yielded larger estimates of effect. On the other hand, not using concealed random allocation resulted in larger estimates of effect, but sometimes it resulted in similar estimates of effect (from harmful to beneficial or vice versa). It is a paradox that the unpredictability of random allocation is the best protection against the unpredictability of the extent to which non-randomised studies may be biased.
We identified nine studies that reported comparisons in 728 infants of paracetamol versus placebo or other pain-reducing interventions. The literature search was updated in May 2016. Paracetamol for heel lance did not reduce pain compared with placebo (water or cherry elixir) or compared with EMLA cream (eutectic mixture of lidocaine and prilocaine). Paracetamol use was associated with a stronger response to pain than was seen with glucose. Paracetamol did not reduce pain in infants exposed to vacuum extraction or forceps at birth, and their response to a subsequent heel lance at two to three days of life was increased compared with placebo. For eye examination, paracetamol was effective in reducing pain compared with water in one study, but the pain response was stronger among paracetamol-treated infants than in infants given 24% sucrose. In infants treated with paracetamol and morphine compared with morphine alone, the total amount of morphine required during the first 48 hours following major surgery to the chest or the abdomen was less in the paracetamol group. Paracetamol did not significantly reduce pain during heel lance. Paracetamol following assisted birth may increase the response to later exposure to painful interventions. Paraetamol may reduce the total need for morphine following major surgery, and further research is needed into this aspect of paracetamol use. In general the studies were of good quality but the numbers of infants enrolled in the different studies were small. The overall quality of evidence was low.
This review examined whether taking magnesium supplements could be recommended for treating adults with high blood pressure from no known cause. It reviewed 12 trials enrolling 545 people, which compared magnesium supplementation with a dummy drug (placebo) or no treatment, and measured blood pressure 8 weeks to 6 months later. The results of trials varied a lot: some trials found magnesium lowered blood pressure much more than placebo, while others found little difference between magnesium and placebo. On average, people receiving extra magnesium achieved slightly lower diastolic blood pressure at the end of trials. None of the studies reported any serious side effects of taking magnesium supplements. However, most included trials were of poor quality, so their results may not be reliable. The trials were not long enough or large enough to measure whether extra magnesium can reduce possible consequences of high blood pressure: death, heart attack or stroke. The review did not find robust evidence that oral magnesium supplementation reduces high blood pressure in adults. Larger, longer duration, better quality trials are needed to clarify whether magnesium supplementation can lower high blood pressure.
We included 20 studies with 5874 participants in the immunogenicity analysis and 5232 in the reactogenicity analysis. In two immunological responses, the combined vaccine achieved lower responses than the separate vaccines for HIB and tetanus. We did not find any significant differences in immunogenicity for pertussis-diphtheria-polio and hepatitis B. Serious adverse events were comparable. Minor adverse events were more common with the combined vaccine. Overall, the level of evidence provided by the studies was low and we could not conclude that the immune responses with the combined vaccine were equivalent to the separate injections.
Review authors searched for studies published from inception until March 2016 and found 13 studies (in total 1053 women), eight of which directly compared 3D SIS versus 2D SIS. Data included all women reporting abnormal menstrual bleeding or difficulty getting pregnant. The number of patients in these studies varied from 23 to 180 women. In all studies, researchers checked the results of 2D SIS and 3D SIS against results obtained when a camera was used to look inside the womb (hysteroscopy); this is expected to give the true picture but is also more painful for the patient. All studies were performed in the usual way. Some studies did not report several items that might have influenced the results. For example, not all studies made it clear that the person evaluating the ultrasound pictures was unaware of the hysteroscopy results, and vice versa. The main problem involving the quality of included studies is insufficient reporting of study methods, resulting in unclear risk of bias for several of the quality domains assessed. Therefore, review authors considered the overall quality of the evidence as low. Low-quality evidence suggests that 3D SIS may be very accurate in detecting polyps and fibroids. Our analysis revealed no clear differences between 2D SIS and 3D SIS. Summary results are higher for 3D SIS but margins of improvement are limited because 2D SIS is already very accurate. Results show that 2D SIS missed a fibroid or polyp in 9 of 100 women and 3D SIS missed a polyp or fibroid in 3 of 100 women who had them. In 4 of 100 women, 2D SIS indicated the presence of polyps or fibroids when there were none, and in less than 1 in 100 women, 3D SIS was wrong. In theory, if both tests were used in a group of 1000 women with abnormal menstrual bleeding, 300 with fibroids or polyps, 27 of the 300 women with polyps/fibroids will be missed by 2D SIS, and 9 of 300 will be missed by 3D SIS. 3D SIS is an alternative to 2D SIS for which the technology and appropriate expertise are available. Both 2D SIS and 3D SIS should be considered alternatives to diagnostic hysteroscopy when intracavitary pathology is suspected in subfertile women and in those with abnormal uterine bleeding.
We looked at randomised controlled trials that compared ambulatory oxygen versus a placebo (normal air). We found four studies on 331 people with a mean age of 71 years. Two of the included studies were from Australia, one from New Zealand and one from Canada. The method of oxygen delivery and the dose of oxygen varied, although equipment in all instances consisted of light-weight or portable cylinders with flow ranging from 3 L/min to 6 L/min. Final follow-up was reported as 12 weeks for three studies and two weeks for the Nonoyama study. We found that ambulatory oxygen therapy reduced breathlessness and decreased the number of patients who felt tired. However, the distance that people could walk in five to six minutes and survival (death rate) did not change. The overall quality of evidence from the studies in this review was moderate. The way the studies were conducted (methods) was not fully reported in all cases. Most studies were lacking the pre-published study plan (protocol). From this review, it is not possible to know whether ambulatory oxygen therapy should be provided during exercise or for day-to-day activities for patients with COPD who are not severely hypoxaemic at rest. This Cochrane plain language summary is up-to-date as of November 2012.
We searched for studies up to May 2017. We included 34 trials in the review, with 2848 participants from 12 countries. The majority of trials (27) were set in an intensive care unit with one in a neonatal intensive care unit. The remaining seven studies were done in an operating department. Participants were infants in three studies with adults (average age of 40 to 69 years) in the remainder. There was no overall difference in the rates of airway blockage, pneumonia or death in adults who were ventilated through heat and moisture exchangers compared to adults ventilated through a heated humidifier. There was some evidence that the occurrence of pneumonia may be lowered by using heat and moisture exchangers that capture less moisture. There was not enough information to make any conclusions about either of these methods in children or infants. The overall low quality of this evidence was low, making it difficult to be confident about these findings.
Amongst the six studies comparing immunosuppressant with placebo, one study, investigating intravenous immunoglobulin (IVIg), showed statistically significant improvement in scores of muscle strength in the IVIg group over three months. Another study investigating etanercept showed some evidence of a longer median time to relapse in the etanercept group, a secondary outcome in this review, but no improvement in other assessed outcomes. The other four randomised placebo-controlled trials assessed either plasma exchange and leukapheresis, eculizumab, infliximab or azathioprine against placebo and all produced negative results. Three of the four studies comparing two immunosuppressant regimes (azathioprine with methotrexate, ciclosporin with methotrexate, and intramuscular methotrexate with oral methotrexate plus azathioprine) showed no statistically significant difference in efficacy between the treatment regimes. The fourth study comparing pulsed oral dexamethasone with daily oral prednisolone and found that the dexamethasone regime had a shorter median time to relapse but fewer side effects. Most of the studies were small (the largest had 62 participants) and many of the reports contained insufficient information to assess risk of bias. Immunosuppressants were associated with significant side effects. The small number of RCTs of immunosuppressants and immunomodulatory therapies are inadequate to decide whether these agents are beneficial in dermatomyositis and polymyositis. Two small trials, one of IVIg in dermatomyositis, the other of etanercept in dermatomyositis suggested that they are beneficial. More RCTs are needed.
The quality of evidence for all outcomes was very low, so we can draw no conclusions about whether light therapy is effective in preventing winter depression. The included study provided no information on side effects of light therapy. Doctors need to discuss with patients considering preventive treatment the advantages and disadvantages of light therapy and other potentially preventive treatments for winter depression, such as drug treatments, psychological therapies or lifestyle interventions. As no available studies have compared these treatments, treatment selection should be strongly based on patient preferences. The review authors recommend that future studies should directly compare light therapy versus other treatments, such as drug treatments, psychological therapies or lifestyle interventions to determine the best treatment for preventing winter depression.
This review of studies was carried out through Cochrane Oral Health, and the evidence is current up to 17 December 2015. We included 38 research studies but only a few (13%) of the studies were well conducted and described. All of the studies took place in ICUs in hospitals. In total there were 6016 participants randomly allocated to treatment. Participants were critically ill and required assistance from nursing staff for their oral hygiene care. Most of the studies involved adults only, but the participants were children in three of the studies, and newborns in one study. We grouped studies into four main comparisons. 1. Chlorhexidine antiseptic mouthrinse or gel compared to placebo (treatment without the active ingredient chlorhexidine) or usual care, (with or without toothbrushing) 2. Toothbrushing compared with no toothbrushing (with or without antiseptics) 3. Powered compared with manual toothbrushing 4. Oral care solutions with other solutions We found high quality evidence that chlorhexidine, either as a mouthrinse or a gel, reduces the risk of VAP from 24% to about 18%. For every 17 people on ventilators for more than 48 hours in intensive care, the use of oral hygiene care including chlorhexidine will prevent one person developing VAP. However, we found no evidence that oral hygiene care with chlorhexidine makes a difference to the numbers of patients who die in ICU, or to the number of days on mechanical ventilation or days in ICU. We have only limited evidence on the effects of toothbrushing (with or without antiseptics) and oral care without toothbrushing (with or without antiseptics) on the risk of developing VAP. Three studies showed some weak evidence of a reduction in VAP with povidone iodine antiseptic mouthrinse compared to placebo/saline. Four studies showed some weak evidence of a reduction in VAP with saline rinse compared to saline swab. There was insufficient evidence to determine whether any of the interventions evaluated in the studies are associated with any unwanted side effects. The evidence presented was limited by how well the included studies were done and reported. Only 13% of the studies were well conducted and well described. For a number of outcomes, there was not enough information to draw a solid conclusion.
This review looked at any restriction of fluids and food in labour compared with women able to eat and drink. The review identified five studies involving 3130 women. Most studies had looked at specific foods being recommended, though one study let women choose what they wished to eat and drink. The review identified no benefits or harms of restricting foods and fluids during labour in women at low risk of needing anaesthesia. There were no studies identified on women at increased risk of needing anaesthesia. None of the studies looked at women's views of restricting fluids and foods during labour. Thus, given these findings, women should be free to eat and drink in labour, or not, as they wish.
Seven studies met the inclusion criteria. However, only five studies with 4798 participants provided data for this review. The mean ages of the participants ranged from 56 to 66 years. The participants all had a history of adenomas and would have had at least one procedure to remove them to achieve a polyp-free colon at baseline.The interventions in the included studies were wheat bran fibre, ispaghula husk, or a comprehensive dietary intervention with high fibre whole food sources used alone or in combination. These were compared to low-fibre (2 to 3 g per day), placebo, or a regular diet. This review found that increasing fibre in a Western diet for two to eight years did not lower the risk of bowel cancer. Paradoxically, after four years participants receiving dietary fibre had higher rates of bowel cancer compared with the control group, with the absolute increase in risk being one percent. The quality of evidence was low. The high risk of bias of included studies, small sample size, large number of missing data and the use of indirect measures gave us little confidence on the findings of this review.
We found 11 studies with 1074 participants. A broad range of people were included in these studies, including people with heart failure, elite athletes, people with restless legs syndrome and otherwise fit and well women. We excluded studies that looked at children, pregnant women, and people being treated with erythropoietin (a hormone that stimulates the production of red blood cells). Intravenous iron may lead to a small increase in the level of haemoglobin in the blood. We also assessed the effect of intravenous iron on quality of life, serum ferritin (iron stored in the body), peak exercise capacity, and milder side-effects of iron administration but we were unable to determine whether or not intravenous iron was of benefit for these outcomes. This is because there were many differences between studies in the types of participants studied, the definition of iron deficiency used, the type of intravenous iron preparation prescribed and the length of the studies. We also tried to collect data on severe side effects and bacterial infection after iron infusion, but we were unable to find any studies that measured these effectively. Because of the many differences between the relatively small number of studies included in this review, we are uncertain about the effect of intravenous iron in non-anaemic iron deficiency beyond saying that it might cause an increase in haemoglobin concentration. Furthermore, the starting level of haemoglobin for people included in this review was considered 'normal' prior to their receiving treatment. Therefore, not only is this increase quite small, but the starting level of haemoglobin was considered adequate according to current guidance, and patients may not even notice an improvement in symptoms. We are not suggesting that intravenous iron is not of benefit for adults with non-anaemic iron deficiency, rather that the current quality of evidence is not good enough to be certain about the effects of these drugs. Overall, the evidence for intravenous iron for the treatment of non-anaemic iron deficiency is of low or very low quality. Whilst intravenous iron might cause a small increase in haemoglobin concentration from an already normal level, we are uncertain about its effects in other outcomes that we examined as part of this review. Further research examining the effects of intravenous iron for the treatment of adults with non-anaemic iron deficiency is required to help answer this research question. The evidence is current to October 2019.
We searched the literature up to June 2016 and found 19 studies, with a total of 1096 adults randomly assigned to receive buffered or non-buffered fluids. Some included trials involved minor surgery in otherwise fit and healthy patients. Other trials analysed outcomes after major surgery in high-risk patients, and five trials included patients undergoing renal transplant surgery. We reran the search in May 2017 and decided that we will deal with one new study of interest when we update the review. Overall results show that the number of deaths was low and provide no evidence that choice of fluids - buffered or non-buffered - influenced the number of deaths that occurred around the time of surgery in the three trials that looked at this outcome (involving 267 participants). We found no differences between groups in the numbers of participants whose kidney function was adversely affected. Analysis of clinical outcomes suggests that buffered fluids are an equally safe and effective alternative to non-buffered fluids for adult patients undergoing surgery. The pH of the blood after surgery was reduced among patients receiving saline (pH 7.32 vs 7.38), suggesting that buffered fluids are associated with less metabolic acidosis. The saline group had higher serum chloride and sodium levels than the buffered fluid group. This might be expected, as members of the saline group were receiving saline and no other electrolytes. Higher serum chloride is a cause of metabolic acidosis. We assessed the quality of evidence as generally moderate, although quality of evidence showing effects of fluid choice on kidney function was low because of the presence of other factors that could affect kidney function in these participants. Evidence shows wide variation in the types of surgery performed and in drivers for and volumes of fluid administered across trials. Reported outcomes varied a great deal between included trials, and some results were expressed in ways that did not allow their inclusion in our findings.
The review found 18 trials in 1174 children who had received this sort of training or another treatment. Although an alarm on its own was better than the dry bed training on its own, there was some evidence that using them together might reduce the relapse rate after stopping alarm treatment, and without the adverse effects of drug treatment. However, both using an alarm and dry bed training needs time and effort from the child and family. There was not enough research comparing complex interventions with other techniques.
This review assessed evidence from 2411 adults with moderate to severe postoperative pain in studies comparing single doses of codeine 60 mg with placebo. The number of individuals achieving a clinically useful amount of pain relief (at least 50%) with codeine compared to placebo was low. In all types of surgery combined, 12 participants would need to be treated with codeine 60 mg for one to experience this amount of pain relief who would not have done so with placebo. The need for use of additional analgesia within 4 to 6 hours was 38% with codeine compared with 46% with placebo, and the mean time to the use of additional analgesia was only slightly longer with codeine (2.7 hours) than with placebo (2 hours). More individuals experienced adverse events with codeine than with placebo, but the difference was not significant and none were serious or led to withdrawal. Other commonly used analgesics, alone and in combination with codeine 60 mg, provide better pain relief. Higher doses of codeine were not investigated in these studies.
We searched for trials comparing glucocorticosteroid avoidance or withdrawal to continuing glucocorticosteroids. Seventeen randomised clinical trials were included, of which 16 trials involving 1347 participants provided numeric data for the meta-analyses. All of the studies assessed adults who had received a liver transplant. Of the 16 randomised clinical trials included in the meta-analyses, 10 trials assessed avoidance of glucocorticosteroids compared with slowly reducing glucocorticosteroids (782 participants) and six trials assessed withdrawal of glucocorticosteroids following a slow reduction compared with a longer reduction or long-term use of glucocorticosteroids (565 participants). Only eight trials reported on the type of donor used. The evidence is current to May 2017. Rejection, severe rejection, and kidney failure may be increased by avoiding or withdrawing glucocorticosteroids compared with continuing glucocorticosteroids. Diabetes mellitus and high blood pressure may be reduced by avoiding or withdrawing glucocorticosteroids compared with continuing glucocorticosteroids. We did not find any difference in survival of the patients, survival of the liver, other adverse effects, or health-related quality of life. We assessed all of the trials we included as being at high risk of bias, which means that they may overestimate the benefits and underestimate the harms of avoiding or withdrawing glucocorticosteroids. The evidence was either low quality or very low quality. There is still some uncertainty about the benefits and harms of avoiding or withdrawing glucocorticosteroids after transplantation. Avoiding or withdrawing glucocorticosteroids appears to increase rejection, severe rejection, and kidney failure but seems to reduce diabetes mellitus and high blood pressure. We found no other obvious benefits or harms of avoiding or withdrawing glucocorticosteroids. More randomised clinical trials are needed to assess avoidance and withdrawal of glucocorticosteroids for liver transplanted patients.
This review of four trials involving 350 participants indicated that this form of treatment can remove large artery blood clots and improve the chances of good recovery despite an increased risk of bleeding in the brain. Long term risk of death is unaffected. However, it is still not clear what the time window is within which treatment is beneficial, what types of arterial blockage are most likely to respond, whether mechanical devices are effective, and whether any of these treatments are better than standard intravenous thrombolytic drugs. More information is needed from forthcoming randomised trials to answer these questions.
We reviewed 89 clinical trials, which included 10,583 people, in total, with OWCL. We included participants of both sexes and all ages (mean 24.5 years); most participants were over 18 years of age. Most studies were carried out in single centres in different countries, mainly in the Far or Middle East, and lasted between two to six months. We included a variety of treatments, such as antimonials, antifungals, and antibiotics, which were administered either directly onto the skin or into a wound, taken by mouth, or physically applied (e.g. laser treatment, heat therapy, etc.). Most of the included studies assessed OWCL caused by two species of parasites known as Leishmania major (L. major) andLeishmania tropica (L. tropica). The evidence is current to November 2016. Two of the most important treatments that we assessed in this review were itraconazole, an antifungal drug taken by mouth, and paromomycin, an antibiotic applied as an ointment. Trials compared both to a placebo tablet or inactive cream (vehicle). Participants received 200 mg itraconazole for six to eight weeks or paromomycin ointment at a concentration of 15% plus 10% urea, twice daily for 14 days. When assessed on average 2.5 months after treatment, more participants were completely cured and cleared of the infection-causing parasites with itraconazole than placebo, but they also had more side effects (mild stomach pain, sickness, and abnormal liver function, as well as headaches and dizziness). When paromomycin ointment was compared with placebo, there was no difference in the number of completely cured participants or the number who were found to be cleared of parasites when assessed on average 2.5 months after treatment, but those in the paromomycin treatment group had more contained skin reactions (such as swelling, blistering, pain, redness, or itch). However, as the certainty of the evidence for these outcomes for these particular comparisons was very low, we are not sure of the accuracy of these results. Neither of our key treatment comparisons assessed the percentage of wounds cured after the end of treatment and speed of healing (i.e. time taken to be cured). The overall certainty of the evidence for the different outcomes in the two main comparisons was very low. Important reasons for this were that studies were not blinded, or had a small sample size, making the results less precise. Some of the evidence only focused on young people, and the results greatly varied between each study. We need more research to fill in the following research gaps: 1) trials of OWCL caused by other types of infection such as L. infantum, L. aethiopica,or L. donovani; 2) involving specific subgroups of people such as children; 3) assessing effectiveness and safety of different anti-Leishmania drugs compared with placebo in self-healing forms of leishmaniasis or with traditional first-choice antimonial treatment in complicated form (defined as more than four lesions over 4 cm in size, located close to an opening or small joints, for which previous treatment has failed); and 4) assessing areas such as wound healing and patient-reported outcomes, such as quality of life. In addition, few studies assessed relevant issues such as drug resistance. International collaboration is required to improve the quality and standardisation of future trials in order to develop a better evidence-based approach.
From our searches we found 14 trials with 607 participants. All trials had problems of design or conduct that might have affected the results. Treatments were studied at birth (eight trials, 326 participants), during relapse (four trials, 181 participants) or at an unknown time (two trials, 100 participants). Our main measure of the success of treatment was function (how well the foot worked in everyday life). Only one trial reported on function; however, data were not available to re-analyse. We analysed data from three trials. When treated at birth, foot position was better after Ponseti plaster casting than after Kite plaster casting. The quality of this evidence was low. When treated at birth, foot position was better after Ponseti plaster casting than after a traditional technique (another type of plaster casting). The quality of this evidence was very low. One trial found Ponseti plaster casting three times per week to be as good as weekly Ponseti casting. This trial did not state at which stage the treatment was done. The quality of this evidence was moderate. Relapse following Kite technique more often required major surgery than relapse following the Ponseti technique. Data were not available to assess the results for adding botulinum toxin A to the Ponseti treatment, using different types of plaster casts in the Ponseti treatment, different foot surgeries or the treatment of relapsed or neglected clubfoot. Most trials did not report on harmful effects. When reported, harmful effects during plaster casting included casts slipping, plaster sores and skin irritation. Harmful effects of infection and skin grafting were reported after surgery. Further well-designed trials are needed to confirm these findings and to decide which is the best treatment for each presentation. The searches for the review are up to date to April 2013.
Controlled trials suggest that quit and win contests may help some smokers to quit, but they have little effect on community smoking rates. Fewer than one smoker in 500 quits because of the contests. Deception levels, where they can be measured, are often high. International quit and win contests are often well supported, especially in developing countries, but there is no clear evidence from trials that they are effective.
The evidence on which this review is based was found to be up to date as of 7 January 2013. A total of seven suitable studies were identified and included in this review; they included 339 children aged from five to 11 years. There were roughly equal numbers of girls and boys in each study and participants were from different ethnic groups depending on where the study was carried out. Studies included were conducted in Turkey, Egypt, China, the United States of America and the United Kingdom. This review found some evidence that the use of a facemask appliance can help to correct prominent lower front teeth on a short-term basis. There was no evidence available to show whether or not these short-term changes will still be maintained until the child is fully grown. There was not enough evidence to support any other types of treatment for prominent lower front teeth. The quality of the evidence for the use of a facemask was moderate to low, whilst the quality of the rest of the evidence was very low.
We conducted a systematic search of the literature with no restrictions on language or country. We included in this review six studies, with a total population of 492 women with breast cancer. Five of the six studies had small samples. Study participants were predominantly 'white', well-educated women with moderate to high income at any stage of breast cancer who were undergoing a range of treatments. Online support groups in these six trials lasted six to 30 weeks and included eight to 15 members. Women participated in these groups between 1.5 and 2.5 hours per week. Investigators reported all trials in English and conducted their research in the USA. None of the included trials measured emotional distress or uncertainty. Women who participated in online support groups showed no improvement in anxiety or quality of life when compared with those in control groups (which included women with similar characteristics who did not participate in online support groups). However, women who took part in online support groups showed a small to moderate reduction in depression when compared with those in control groups. Results revealed no difference in depression between groups led by peers and those led by health professionals. However, women taking part in standard online groups (run by participants without prompting from health professionals) reported a greater reduction in depression and anxiety than those in other types of online groups (in which women were asked specifically by the health professional to respond to one another's need for support). Small studies of low or very low quality attributed mainly to poor study design and other shortcomings have provided evidence on the effectiveness of online support groups for women with breast cancer. Large, rigorous trials including ethnically and economically diverse participants are needed to provide robust evidence on the effectiveness of online support groups for women with breast cancer.
We identified 33 medical trials involving 2242 participants: 68% were male, and the mean age was 42 years. Most studies compared antidepressants to placebo (22 studies), but some compared one antidepressant to antidepressant (five studies), to another type of medicine (four studies), or to psychotherapy (a talking treatment; two studies). The average duration of the trials was 10 weeks (range 3 to 26 weeks). A total of 18 trials took place in the USA, and the others were in Europe, Turkey, and Australia. The antidepressant used in most of the trials was sertraline; the others were: amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. The studies used 49 different rating scales and varied in terms of design, quality, participant characteristics, tested medicines, services provided, and treatments administered. A total of 19 studies reported the source of funding (public funds: six studies; pharmaceutical industry: two studies; both funds: 10 studies). Only four trials reported a declaration of the authors reporting possible conflicts of interest. In the 22 studies comparing antidepressants to placebo, antidepressants may have reduced the severity of depression but we are uncertain whether it increased the number of people with clinical beneficial effects from the reduction of depression severity (response to treatment, i.e. people who halved the severity of depression). However, we found no difference between antidepressants and placebo in other relevant outcomes related to the severity of depression, such as the number of people without depression at the end of the trial (remission). In addition, we found that the administration of antidepressants probably reduced alcohol consumption evaluated as the number of participants abstinent during the treatment (higher among participants who received antidepressants compared to placebo) and the number of drinks consumed per drinking days (lower among participants who received antidepressants compared to placebo). However, similarly to what we found for the severity of depression, we also observed that the administration of antidepressants did not affect other relevant outcomes related to alcohol dependence, such as the rate of abstinent days, number of heavy drinkers, and time before first relapse. In terms of safety issues, the rate of people withdrawing from treatment due to side effects (undesirable effects such as dry mouth) may not differ between antidepressants and placebo. There were few studies comparing one antidepressant to another antidepressant or to other interventions, and these had a small number of participants and the same comparison was not made by more than one study, and were therefore not informative. The quality of the included studies was low or moderate for depression severity, abstinence from alcohol, rate of people withdrawal for medical reasons, and dropouts. In subgroup analyses, in the case of single types of medicines, and comparisons with other medicines, the findings of the review were limited by the small number of available studies. There is low-quality evidence supporting the use of antidepressants in the treatment of people with co-occurring depression and alcohol dependence. Antidepressants have positive effects on certain relevant outcomes related to depression and alcohol use but not on equally relevant other outcomes. However, the risk of developing side effects appears to be minimal, especially for the newer classes of antidepressants.
We wanted to discover whether colchicine alone or added to other medications is better or worse than alternative therapies in preventing pericarditis. We have reviewed all randomised controlled trials about the effect of colchicine in preventing recurrence of pericarditis in people with pericarditis. We found four trials involving 564 participants, who were followed up for at least 18 months. Two studies examined the use of colchicine in people with recurrent pericarditis and two examined the use of colchicine in people with a first episode of pericarditis. The evidence is current to August 2014. The trials showed that people taking colchicine have a lower risk of developing pericarditis recurrence and a higher proportion experience symptom relief. It is expected that at 18 months, one pericarditis recurrence can be avoided for every four people receiving colchicine with NSAIDs rather than NSAIDs alone. Adverse effects were reported in all trials and affected 15 people (9%) of the 162 taking colchicine. Adverse effects included abdominal pain, nausea and vomiting. Two studies were designed so that participants knew the type of intervention they were taking and people in the comparison group had no dummy pill. The results of these studies could exaggerate the effects of the drug. The evidence suggests beneficial effects of colchicine in preventing recurrence of pericarditis, however this is based on a limited number of small trials. More trials are currently being done and we await their results to see if the benefits of colchicine can be further confirmed.
We found two studies that examined a psychosocial intervention for women who had undergone removal of their fallopian tubes and ovaries to reduce their risk of tubo-ovarian cancer. One randomised controlled trial (a study in which participants are assigned to one of two or more treatment groups using a random method) assessed a mindfulness-based stress reduction training programme for menopausal symptoms after risk-reducing surgery. Whilst there was improvement in the menopause-specific quality of life scores in the short and the long term for women with menopausal symptoms, the intervention was not associated an with improvement in sexual functioning or distress. Women who participated in a non-randomised study all received the study intervention and scored themselves on certain items related to psychosexual functioning and psychological adjustment before and after the intervention (targeted sexual-health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies). They also received a group psychoeducation session and telephone counselling. The outcomes were based on the differences between the before and after scores. All women recruited to the study were at risk of tubo-ovarian cancer based on having a harmful or faulty BRCA gene, but there was no personal history of tubo-ovarian cancer in the group studied. No studies reported on social and psychological interventions following risk-reducing surgery to have breast tissue removed in BRCA carriers. The certainty (quality) of the evidence ranged from moderate to very low, with only one randomised controlled trial and one non-randomised study that had no comparator included in the review. Both studies involved small numbers of women. The limited, moderate- to very low-certainty evidence meant that we were unable to draw any conclusions regarding psychosocial interventions following risk-reducing surgery in female BRCA carriers on improvement in quality of life and psychological (emotional) adjustment. Further research is required to determine how best to support women who choose to have risk-reducing surgery.
This review summarized trials evaluating the effects of interventions aiming to increase the diagnosis of tuberculosis and reduce the number of undiagnosed tuberculosis cases in communities. After searching for relevant trials up to 19 December 2016, we included 17 studies conducted in sub-Saharan Africa (nine studies), Asia (six studies), and South America (two studies). Why does tuberculosis go undiagnosed and how might programmes improve this? Tuberculosis is a chronic infectious disease that affects over 10 million people worldwide, with an estimated four million tuberculosis patients remaining undiagnosed each year. Interventions such as outreach tuberculosis screening with or without health promotion that actively screen for tuberculosis among individuals presenting with symptoms of tuberculosis, may increase detection of microbiologically confirmed tuberculosis cases. These interventions may improve treatment outcomes by increasing the number of tuberculosis patients who are cured and complete treatment. However, we do not know if these interventions reduce either tuberculosis treatment failure, or tuberculosis-associated death or long-term tuberculosis burden in moderate- and high-tuberculosis settings. What the research says House-to-house screening for active tuberculosis, and organizing tuberculosis diagnostic clinics nearer to where people live and work, may increase tuberculosis case detection in settings where the prevalence of undiagnosed disease is high (low-certainty evidence). These people may have higher levels of treatment success and lower levels of default from treatment (low-certainty evidence). There was insufficient evidence to determine if health promotion activities alone increase tuberculosis case detection (very low-certainty evidence). There was also insufficient evidence to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence, as the only study to evaluate this found no effect after four years (very low-certainty evidence).
We identified 60 studies of vitamin D preparations in people with CKD and requiring dialysis involving 2773 people. No studies were designed to understand the effect of vitamin D therapy on risks of death. Vitamin D agents suppress PTH significantly compared with no treatment, however also increase both circulating calcium and phosphorus levels. Intravenous vitamin D may lower PTH more than oral vitamin D. Few studies directly compare newer vitamin D therapies with earlier (and presently more common treatment options; calcitriol and alfacalcidol); newer treatment options therefore cannot be recommended as superior to established treatments. In the future, new studies will required to know if vitamin D effects on parathyroid function improve survival, bone pain, and need for parathyroid removal by surgery. It is possible that vitamin D compounds are beneficial to patients regardless of their effects on parathyroid hormone. This can only be adequately evaluated by conducting specific studies that are large enough to be sure of any treatment differences.
We set out to undertake a systematic review comparing randomised controlled trials that examined the efficacy and safety of PD and BTX injection in people with achalasia. We searched databases (MEDLINE, EMBASE, ISI Web of Science, and The Cochrane Library) in April 2014 for reports of relevant randomised controlled trials. Seven randomised controlled trials were identified for inclusion in the review, and five were suitable for meta-analysis. Meta-analysis suggested that, although both interventions had similar initial response rates, the remission rates at six and 12 months were significantly greater with PD than with BTX injection.
However studies have focused on heart protection rather than residual kidney function. The aim of this review was to assess the benefits and harms of ACEis and ARBs therapy for preserving residual kidney function in PD patients. Six studies (257 patients) were included (three ARB studies, one ACEi study and ACEi versus ARB studies). Long-term use (12 months or more) of an ARB showed a significant benefit in preserving residual kidney function in continuous ambulatory PD (CAPD) patients compared with other antihypertensive drugs, although there was no significant benefit when an ARB were used for less than six months). One study showed that compared with other antihypertensive drugs, long-term use of the ACEi ramipril showed a significant reduction in the decline of residual kidney function in patients on CAPD as well as anuria rate. While dizziness and cough are the main adverse events when an ACEi is used, only one study comparing an ARB with an ACEi reported this outcome and no significant difference between the two groups were found. While the use of an ARB or an ACEi may both be useful in preserving residual kidney function, the small number of studies and small number of patients enrolled means there is currently insufficient evidence to support the use of an ACEi or an ARB as first line antihypertensive therapy in PD patients.
In the only study which addressed this question, the use of an amoxycillin and clavulanic acid antibiotic regimen had no effect on clinical pregnancy rate despite demonstrating a reduction in upper genital tract colonisation. The effect on live birth rate is unknown. The findings of this review do not support the use of an amoxycillin and clavulanic acid antibiotic regimen prior to ET for the purposes of improving IVF success. The effect of alternative antibiotic regimens on IVF outcomes is unknown and needs further research.
We planned to report evidence from clinical trials which compared different disease-modifying drugs compared with placebo (or dummy treatment), with each other or with no treatment. However, we were disappointed that we could not find any completed randomised controlled trials of these treatments or any evidence from non-randomised controlled trials. We suggest that there should be a randomised controlled trial to look at the effects and the safety of using disease modifying anti-rheumatic drugs to slow or stop the progression of arthritis in people with cystic fibrosis.
This review reports that low molecular weight heparin reduces the incidence of distal DVT diagnosed but the clinical benefits of this are uncertain. The review authors identified four completed studies from three countries that randomly assigned a total of 527 adults to low molecular weight heparin (LMWH) or no intervention or placebo. The mean age of participants ranged from 31 to 44 years and nearly three quarters were male. The relative risk (RR) of thrombotic events was 0.16 (range 0.05 to 0.52). The number needed to treat to prevent one thrombotic event was 17. All the blood clots were distal and were mainly diagnosed by sonogram. Adverse events were most common in the intervention group. The most common complication was minor bleeding with a RR of 2.23 (range 0.99 to 4.99). The number needed to harm was 20. No completed studies were found that looked at mechanical devices such as graduated elastic stockings or intermittent pneumatic compression, for patients immobilized in bed.
We analysed 47 randomised controlled trials (RCTs). A RCT is a type of study in which the people being studied are randomly allocated one or other of the different treatments being investigated. This type of study is usually the best way to evaluate whether a treatment is truly effective, i.e. truly helps the patient. A systematic review systematically summarises the available RCTs on a subject. A total of 5102 women participated. Comparisons were vaginal versus abdominal hysterectomy (nine trials, 762 women), laparoscopic versus abdominal hysterectomy (25 trials, 2983 women), laparoscopic versus vaginal hysterectomy (16 trials, 1440 women) and laparoscopic versus robot-assisted hysterectomy (two trials, 152 women); in addition there were studies in which three comparisons were made (four trials, 410 women). There were also studies included in which different types of laparoscopic hysterectomies were compared, including single-port versus multi-port (three trials, 203 women), total laparoscopic hysterectomy versus laparoscopic-assisted vaginal hysterectomy (one trial, 101 women) and mini-laparoscopic versus conventional laparoscopic hysterectomy (one trial, 76 women). The main outcomes were return to normal activities, satisfaction, quality of life and surgical complications. We found that vaginal hysterectomy resulted in a quicker return to normal activities than abdominal hysterectomy. There was no evidence of a difference between them for our other main outcomes. Laparoscopic hysterectomy also resulted in a quicker return to normal activities than abdominal hysterectomy. However, laparoscopic hysterectomies had a greater risk of damaging the bladder or ureter. There was no evidence of a difference between laparoscopic and vaginal hysterectomy or between laparoscopic and robot-assisted hysterectomy for our main outcomes. We conclude that vaginal hysterectomy should be performed whenever possible. Where vaginal hysterectomy is not possible, both a laparoscopic approach and abdominal hysterectomy have their pros and cons and these should be incorporated in the decision-making process. The evidence is current to August 2014. The evidence for most comparisons was of low or moderate quality. The main limitations were poor reporting of study methods and wide confidence intervals around the estimate of effect.
This review included data from 11 trials conducted in Australia, Europe and North America. The studies followed up 2159 participants with drusen (3580 eyes) to two years, of which six studies (1454 participants) included people with one eye randomised to treatment and one to control. Four studies (850 eyes) used subthreshold photocoagulation. Three out of four studies using laser subthreshold photocoagulation were sponsored by the laser producer. These studies showed that laser photocoagulation of drusen leads to their disappearance. However, laser photocoagulation of drusen did not reduce the risk of developing CNV, which was about 10% at three years in untreated participants. A smaller number of studies reported on the development of geographic atrophy, that is, atrophy in the centre of the macula, but these studies were inconclusive and the effect of laser treatment of drusen on the development of geographic atrophy was uncertain. The risk of visual loss was similar in treated and untreated groups. There was no suggestion that a benefit may exist with subthreshold photocoagulation. The overall quality of the evidence was high regarding failure to prevent CNV, but it was low for prevention of atrophy due to the small number of participants for whom this outcome was assessed.
We searched for clinical studies that compared starting treatment of hypertension in adults with monotherapy versus starting with combination therapy. Studies had to report results in terms of deaths, events due to diseases of the heart or the vessels (heart attack, stroke, or heart failure), deaths due to diseases of the heart or the vessels, or any health-related serious side effects. We only selected studies with 50 or more people per group and that lasted at least 12 months. The evidence is current to April 2019. In this update we included one new study, for a total of four studies in the review involving 349 people treated with combination therapy and 419 treated with monotherapy. However, data were insufficient to answer our review question. There is a need for more and larger studies that compare monotherapy with combination therapy as the initial treatment of hypertension.
This is an update of a review published in 2009. New searches in March 2015 identified three new studies, making 18 studies with 3714 participants altogether, 1902 of whom were treated with diclofenac and 1007 with placebo. Diclofenac potassium is a rapidly absorbed formulation, and the 50 mg dose provided the largest amount on information. With this dose of this formulation, more than 6 in 10 (64%) participants had effective pain relief, compared with fewer than 2 in 10 (17%) with placebo (high quality evidence). Adverse events occurred at similar rates with diclofenac and placebo in these single dose studies (moderate quality evidence). There were few serious adverse events or withdrawals due to adverse events. Diclofenac potassium represents a useful option in controlling acute pain.
We included randomised controlled studies published up to June 2016. We found 17 studies, with 3149 women who had just delivered by CS. In these studies, a group of women chewed gum and a second group did not, receiving usual care. The studies were conducted in nine countries (mostly low- to middle-income countries) and were different in many aspects. For instance, some studies included only women having their first baby and others included women with a previous CS; some studies included only elective (pre-scheduled) CS and others also included emergency CS. The way that gum was given also differed in the studies; in some the women started chewing gum right after the CS and in others they waited for up to 12 hours. Also, the women could not be blinded to receiving the gum. The combination of the results (in a meta-analysis) of these studies showed that the women who chewed gum after a CS had an earlier return of their bowel function. On average, they passed gas seven hours earlier (13 studies, 2399 women). This effect was consistent for first versus repeat CS, time spent chewing gum per day, early feeding versus nothing by mouth until the return of intestinal function, elective versus non-elective or emergency CS, and length of time after CS when gum-chewing was initiated. The quality of the evidence for this outcome was very low. The women chewing gum were at least half as likely to have 'ileus' (a combination of symptoms such as bloating, cramping, nausea, vomiting and inability to defecate) than the women who did not chew gum (four studies, 1139 women, low-quality evidence). Gum chewing reduced the time to first defecation to about nine hours earlier (11 studies, 2016 women, very low-quality evidence) and the time to hospital discharge by some eight hours (seven studies, 1489 women). Only three out of 925 women complained about having to chew gum and there were no reports of adverse effects associated with gum-chewing (eight studies, 925 women, low-quality evidence). None of the studies assessed women's satisfaction in relation to chewing gum. The overall quality of the evidence was low to very low, mostly due to lack of blinding of the participants (the women knew they were chewing gum) and heterogeneity between the studies. The available evidence suggests that gum-chewing in the first 24 hours after a CS is a well-tolerated simple, low-cost, safe and easy intervention that enhances early recovery of bowel function, improves maternal comfort and potentially reduces hospital costs. Further research is necessary to establish the optimal regimen of gum-chewing (when to start, number and duration of sessions per day) to enhance bowel function recovery and to assess potential adverse effects and women's satisfaction with this intervention.
This review found that fluoroquinolones like ciprofloxacin, levofloxacin, lomefloxacin, ofloxacin or prulifloxacin have equivalent effects and equivalent success rates in CBP patients. If atypical bacteria like chlamydia are suspected to cause CBP, macrolide antibiotics such as azithromycin may achieve better results compared to the fluoroquinolone ciprofloxacin. It must be taken into account that some of the studies that have been performed are of poor quality or have been performed on small numbers of participants. More studies are needed, focusing on new agents or on optimized doses of currently prescribed antibiotics.
We identified 26 randomised controlled trials, involving 21,704 participants, that examined the effect of adrenaline or vasopressin on survival after cardiac arrest that occurred in and out of hospital and in adults and children. Some studies compared adrenaline in standard doses with placebo (dummy medication); some examined standard-dose versus high-dose adrenaline; and others compared vasopressin alone or vasopressin plus adrenaline to standard doses of adrenaline. The source of funding was not stated in 11 of the 26 studies. The study drugs were provided by the manufacturer in four of the 26 studies, but neither drug represents a profitable commercial option. The other 11 studies were funded by organisations such as research foundations and government funding bodies. The studies found evidence that adrenaline was effective at restarting the heart and helping people recover enough to go home from hospital. However, there was no evidence that any of the drugs improved survival with a good neurological outcome. The overall quality of evidence ranged from low to moderate (for studies comparing adrenaline to placebo), but mainly low or very low for the other comparisons, due to risks of bias within the studies. Many of these studies were conducted more than 20 years ago. Treatment has changed in recent years, so the findings from older studies may not reflect current practice. The studies examined the drugs in many different situations (in and outside of hospitals, at different dosages, and in both adults and children), which may make combining findings misleading.
This review looked at the effects of attaching artificial teeth either the same day that the implant was placed, or early (after only 6 weeks) compared to the usual delay of at least 3 months. Some studies also compared the artifical tooth being attached so that it did not touch the opposite tooth (non-occlusal loading). The search of studies was updated on 8th June 2012. The review found no evidence that attaching artificial teeth either immediately, after 6 weeks (early) or after at least 3 months (conventional) led to any important differences in the failure of the implant or the artifical tooth, or to the amount of bone which surrounded the implant (any bone loss would be an undesirable consequence). More research is needed in this area.
We identified 38 studies and came to the conclusion that misoprostol is the drug of choice for medical pregnancy termination, preferably in combination with mifepristone which facilitates the effectiveness of misoprostol. Misoprostol works best when it is administered into the vagina. Women who had previously given birth could take misoprostol by mouth (under the tongue). Irrespective of the medication used for second trimester termination there is a considerable risk of surgical intervention because of vaginal bleeding or incomplete abortion.
We searched the medical literature for the information from clinical studies and found 11 randomized controlled studies that met our inclusion criteria. We included 11 studies randomising a total of 833 women, although nearly all the results we report are based on single studies with small numbers of participants. We were unable to pool the findings in any meta-analyses due to each study using different forms of relaxation in different comparisons, to prevent preterm births in seven studies and to treat preterm labour in five with insufficient information. No valid conclusion can be summarized from this review. For women not in preterm labour, relaxation therapy (alone or combined with standard treatment) reduced maternal stress compared with routine prenatal care and increased birthweight with fewer cesarean deliveries in a single study. For women in preterm labour, there was no evidence of benefits or harms. More rigorous studies are required in order to assess the effects of relaxation therapies in preventing and treating preterm labour.
We included 90 studies involving almost 200,000 people, with 88 of these studies carried out in Africa in field settings. Study design and conduct were poorly reported against current expectations. Based on our statistical model, we found: • Among the urine strips for detecting urinary schistosomiasis, the strips for detecting blood were better than those detecting protein or white cells (sensitivity and specificity for blood 75% and 87%; for protein 61% and 82%; and for white cells 58% and 61%, respectively). • For urinary schistosomiasis, the parasite antigen test performance was worse (sensitivity, 39% and specificity, 78%) than urine strips for detecting blood. • For intestinal schistosomiasis, the parasite antigen urine test, detected many infections identified by microscopy but wrongly labelled many uninfected people as sick (sensitivity, 89% and specificity, 55%). What are the consequences of using these tests? If we take 1000 people, of which 410 have urinary schistosomiasis on microscopy testing, then using the strip detecting blood in the urine would misclassify 77 uninfected people as infected, and thus may receive unnecessary treatment; and it would wrongly classify 102 infected people as uninfected, who thus may not receive treatment. If we take 1000 people, of which 360 have intestinal schistosomiasis on microscopy testing, then the antigen test would misclassify 288 uninfected people as infected. These people may be given unnecessary treatment. This test also would wrongly classify 40 infected people as uninfected who thus may not receive treatment. Conclusion of review For urinary schistosomiasis, the urine strip for detecting blood leads to some infected people being missed and some non-infected people being diagnosed with the condition, but is better than the protein or white cell tests. The parasite antigen test is not accurate. For intestinal schistosomiasis, the parasite antigen urine test classifies many microscopy negative people as being infected. This finding may be explained by the low sensitivity of microscopy.
We searched for evidence in September 2017 but did not find any randomised controlled studies relating to our area of interest. We excluded one study and one other study is not yet complete. We cannot say whether or not antenatal education has an effect on perineal wound healing after childbirth among women who have birthed in a hospital setting. We do not know from randomised controlled trials what the benefits and harms of this education might be. More research is this area is needed to determine the impact of education delivered before childbirth on perineal wound healing in women who have birthed in a hospital setting. Trials may also examine the outcome on related issues including infection rate, re-attendance or re-admission to hospital, pain, health-related quality of life, maternal bonding, and negative emotional experiences relating to a perineal wound. A large proportion of childbearing women experience a perineal wound in childbirth, and these wounds are known to have a significant physical, psychological and economic impact. Future research could examine the potential benefits of a tailor-made education package to be delivered to this cohort of women, as there is currently no evidence to support this.
We gathered evidence for this Cochrane Review by examining three clinical trials with over 800 children included. All three clinical trials showed a reduced rate of pneumococcal infection in children with SCD receiving penicillin preventatively. Two of these trials looked at whether treatment was effective. The third trial followed on from one of the early trials and looked at when it was safe to stop treatment. Adverse drug effects were rare and minor. However, there were problems with children keeping to the treatment schedule and with the development of antibiotic resistance. The quality of the evidence for both primary and secondary outcomes (end result) was judged to be low. We conclude that penicillin given preventatively reduces the rate of pneumococcal infections in children with SCD under five years of age. The risk of infection in older children is lower, and the follow-on trial did not show a significant increase in risk when regular penicillin was halted at five years old. Further research is needed to look at how commonly bacteria develop that are resistant to treatment and how clinically important this is.
Population based studies suggest the prevalence of pes cavus is approximately 10%, and its cause is primarily neuromuscular (for example Charcot-Marie-Tooth disease) or idiopathic (unknown) in nature. It has been estimated that 60% of people with cavus feet will experience chronic foot pain at some time in their life, most commonly beneath the forefoot (for example metatarsalgia, sesamoiditis) or heel (for example plantar fasciitis). Conditions such as these are thought to be the result of abnormal pressure distribution across the sole of the foot during walking. Many conservative therapies and surgical procedures have been recommended for cavus-related foot pain. In particular, foot orthoses (aids applied and worn on the outside of the body to support the bony structures) customised to an individual's foot shape are increasingly prescribed by podiatrists, physiotherapists, orthopaedic surgeons and rehabilitation specialists for people with pes cavus pain. This updated review analysed four relevant trials, but only one fully met the inclusion criteria. This trial with 154 adults showed that custom-made foot orthoses can reduce and redistribute plantar foot pressure and subsequently decrease foot pain by approximately 75%. Some biomechanical outcomes, such as pressure distribution, improve with custom-made foot orthoses and footwear, but many other biomechanical outcomes, such as foot alignment or muscle activity, do not improve with botulinum toxin or off-the-shelf foot orthoses, respectively. More research is needed to determine the effectiveness of other interventions for people with painful high-arched feet.
The evidence is current to 11 October 2019. We included studies that randomly assigned adults to intervention groups comparing the two techniques described above. We found six studies including a total of 562 participants. Five studies involved abdominal surgery, and one involved orthopaedic surgery. No studies involved emergency surgery nor patients suffering from serious medical conditions before surgery. The number of deaths was slightly lower in the GDFT group compared with the RFT group, but this may be due to chance. No difference in the frequency of major complications was observed between the two groups. In addition, no differences were observed between RFT and GDFT groups in the following outcomes: length of hospital stay, surgery-related complications (related directly to the operation site, e.g. problems with wound healing), non-surgery-related complications (related to problems with other organs, e.g. heart or lungs), renal failure, and quality of surgical recovery. We judged the certainty of evidence obtained for this review as very low because conclusions are based on very small numbers of participants in included studies, the quality of included studies is low, and studies were performed only on selected groups of patients that did not reflect the real population of people undergoing surgery. This means that new studies are very likely to change the results of this review. The review does not answer the question of whether results would be the same for adults who have other serious health problems before surgery, or for adults undergoing other types of surgery besides abdominal surgery and orthopaedic surgery.
We identified 33 studies with 1853 participants. Studies included a wide range of tasks to practice, including lifting a ball, walking, standing up from sitting and circuit training with a different task at each station. The evidence is current to June 2016. In comparison with usual care (standard physiotherapy) or placebo groups, people who practiced functional tasks showed small improvements in arm function, hand function, walking distance and measures of walking ability. Improvements in arm and leg function were maintained up to six months later. There was not enough evidence to be certain about the risk of adverse events, for example falls. Further research is needed to determine the best type of task practice, and whether more sustained practice could show better results. We classified the quality of the evidence as low for arm function, hand function and lower limb functional measures, and as moderate for walking distance and functional ambulation. The quality of the evidence for each outcome was limited due poor reporting of study details (particularly in earlier studies), inconsistent results across studies and small numbers of study participants in some comparisons.
We found 30 randomised trials of iron supplementation in blood donors with a total of 4704 participants. We found that some of the studies did not report details of their design very well and people in some of the studies left the study early and did not contribute data. Combining the results from four studies, we have shown that around 3% of donors who were given iron supplements were unable to give blood when they next came to donate because the levels of iron in their blood were too low, compared with 10% of donors who did not take iron. More than this, 4% of iron-supplemented donors were unable to give blood at any future donation due to low iron levels, compared with around 20% of donors not given iron supplementation. However, 29% of donors who took iron tablets experienced side effects compared with 17% of donors who were given dummy tablets. Combined data from two studies showed that the iron-supplemented donors had nearly five times the chance of stomach upsets and changes in their taste compared to donors who did not take these tablets. Due to the issues around how reliable the studies were, the quality of evidence is moderate and these results could change with more research. Donors can benefit from iron tablets but the rate of side effects is high, which means in practice that giving all donors iron tablets is unlikely to be acceptable and we do not know whether giving iron causes extra problems over a long period of time. Blood services may target iron supplementation at groups or individuals who are at risk of iron deficiency or may try to reduce deferral by adjusting donation intervals to suit the donor's ability to give blood without becoming iron deficient or to give specific dietary advice to donors.
The evidence is current to January 2018. We found 33 cohort studies examining liver adverse effects after treatment for childhood cancer. There were 7876 cancer patients included that were treated for different types of childhood cancer, especially with chemotherapy, radiotherapy, and bone marrow transplantation. The average follow-up duration in the studies that reported this varied from two years after the end of treatment to 25 years since primary cancer diagnosis. We found that 1% to 53% of the childhood cancer survivors developed adverse effects on the liver after cancer treatment, measured by liver enzymes in the blood. Radiotherapy to the liver increases the risk of liver late adverse effects. In addition, busulfan, thioguanine, or liver surgery may increase the risk as well. Also, survivors with chronic viral hepatitis, metabolic syndrome, higher body mass index, higher alcohol intake, statin use, non-Hispanic white ethnicity, longer time since cancer diagnosis, and older age at cancer diagnosis seemed to have an increased risk of liver adverse effects. All studies had problems related to the quality of the evidence.
This is an update of the original review published in 2009 for which no studies met the inclusion criteria. For this update, in a search of the published literature in November 2014 we found one moderate quality randomised controlled trial which compared ABH (Ativan®, Benadryl®, Haldol®) gel, containing haloperidol and two other medications, to placebo. The trial showed no difference between ABH gel and placebo. However it has previously been shown that haloperidol is not absorbed after applying ABH gel, so this result is not surprising. We identified a trial of haloperidol for nausea and vomiting in patients with cancer, with initial results presented at a conference. This suggests that haloperidol is effective in 65% of patients, but the results were not fully published at the time of our review. A further trial has opened in Australia, comparing haloperidol with another medication used for nausea, methotrimeprazine (levomepromazine).
This systematic review found only one small study (20 participants) of good methodological quality, which reported no significant difference between surgical and chemical sympathectomy for relieving neuropathic pain. Potentially serious complications of sympathectomy are well documented in the literature, and one (neuralgia) occurred in this study. The practice of sympathectomy for treating neuropathic pain is based on very weak evidence. Furthermore, complications of the procedure may be significant.
In this review we found that dietary, physical activity, or behavioral interventions produced significant improvements in weight among persons with prediabetes and a significant decrease in diabetes incidence. Modest, but not statistically significant improvements were noted in the few studies that examined blood sugar control, blood pressure, and lipid levels. No data on quality of life or mortality were found.
Three randomised controlled trials with a total of 246 participants have been conducted to assess the efficacy and safety of sulthiame as monotherapy in epilepsy. Two studies have been conducted on benign epilepsy of childhood with centrotemporal spikes, and one study has been conducted on generalised tonic-clonic seizures. The quality of the evidence is limited by small sample sizes, significant risk of bias and the absence of data on important outcome measures and, in the case of one study, the lack of an English translation of the full-text manuscript. As a result, this review can draw no meaningful conclusions on the efficacy or safety of sulthiame as monotherapy in epilepsy. Our search (carried out in October 2013) revealed two ongoing studies on the use of sulthiame as monotherapy in benign epilepsy of childhood with centrotemporal spikes, the results of which may facilitate a more meaningful analysis in future updates of this review.
This review has shown that regular use for at least seven days of inhaled beta-2 medicines that relieve airways obstruction and can also improve the symptoms associated with chronic obstructive pulmonary disease (COPD) in most patients but not all. Patients are far more likely to prefer treatment with these type of medicines than with placebo, and less likely to fail or drop-out from treatment when treated with such medicines. Regular treatment with such inhaled medicines should be reserved for those patients who report symptomatic and clinical benefit from their use. Newer, long acting bronchodilators are currently available, and they may be more practical and/or effective in these patients. However, this review indicates that these older inexpensive drugs are effective in the treatment of COPD.
We set out to compare the two forms of local anaesthesia for cataract surgery. Our review showed that pain control and paralysis of the eye muscles to paralyse movement of the eye ball (akinesia) and allow surgery are no different for the two types of anaesthesia. The need for additional injections of local anaesthetic was higher with peribulbar anaesthesia (four trials). Only one case of bleeding behind the eye occurred and this was with retrobulbar anaesthesia (in one trial). The acceptability of the two methods to patients were similar in the two studies that reported on this outcome. None of the trials reported any life-threatening complications. There was a moderate risk of bias in the included trials.
The quality of evidence is generally low to very low. Most studies did not evaluate dietary interventions for key review outcomes, particularly mortality and morbidity. However, a few study outcomes with moderate-certainty evidence focused on dietary intake and physical measurements. Included studies compared dietary interventions versus control or usual care. We pooled data from similar randomised controlled trials (RCTs) to provide a summary estimate of the effects of an intervention, and we judged how confident (certain) we were of these findings by using an established method (GRADE). We identified 25 RCTs involving 27 different comparisons. For some outcomes, we found absence of evidence for dietary interventions. We found some evidence showing that dietary interventions probably did not modify energy intake; however, some evidence shows what is probably a slight increase in fruit and vegetable intake (moderate-certainty evidence). Evidence on dietary fibre was mixed for different advice on weight reducing or healthy eating. Dietary interventions compared to control probably improved the Diet Quality Index (moderate-certainty evidence). For physical measurements, we found a probable reduction in body mass index (BMI) with dietary interventions compared to controls (moderate-certainty evidence) but little evidence showing any change in waist-to-hip ratio (low-certainty evidence). For quality of life (QoL), results were mixed due to the wide variety of tools used. No adverse events were reported. Available evidence shows that dietary interventions can be helpful in modifying fruit and vegetable servings and diet quality; modification of fibre intake was variable, and some benefits were seen for anthropometric measurements, including BMI. Most of the evidence is based on women with breast cancer, so more research is needed for patients with other cancers. Gaps identified in the evidence involved the use of new technologies, comorbidities, and body composition data.
We conducted a systematic review to summarize available information on the diagnostic value of different aspects of physical examination. We included 19 different studies in which a wide variety of tests were investigated, such as the straight leg raising test, absence of tendon reflexes, or muscle weakness. The results show that most individual tests carried out during physical examination are not very accurate in discriminating between patients who have, or do not have a herniated disc with sciatica. However, most of the studies were conducted in highly selected patients who had already been referred for surgery, and only one study was carried out in a primary care population. Furthermore, better diagnostic performance of physical examination may be expected when combinations of tests are used, including information from both the patient history and physical examination. However, more research is needed to investigate the performance of such test combinations.
We found seven studies that randomly allocated a total of 225 participants to cognitive training or to a control group. Treatment lasted from four to eight weeks. All the cognitive training interventions were delivered by computer. The control groups received either no intervention or a control intervention such as language or motor exercises or participation in recreational activities. We found no difference between people who received cognitive training and people in the control groups in global cognition shortly after treatment ended. There was no convincing evidence of benefit in specific cognitive skills and no benefit shown in activities of daily living or quality of life. However, these findings were based on a small number of participants in a small number of studies. The overall certainty of the evidence was low, meaning that the results of further research could differ from the results of this review. We found no good evidence that cognitive training is helpful for people with Parkinson's disease and dementia or MCI. The included studies were small and had flaws that may have affected the findings. The certainty of the results was low, and further studies are needed before we can be confident whether or not cognitive training is effective for this group of people.
The purpose of this systematic review was to evaluate the effectiveness and safety of CMH in alleviating chemotherapy-induced short term side effects for women either undergoing chemotherapy or having recently undergone chemotherapy. Short term side effects are those that occur during the course of the treatment and generally resolve within months of the completion of the therapy and affect up to 60% of patients.They include nausea and vomiting, mucositis (inflammation of the mucous membranes lining the digestive tract from the mouth down to the anus caused by chemotherapy); neutropenia (a decrease in white blood cells caused by chemotherapy); myelosuppression (a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets), and fatigue (loss of energy and tirdness). This review found seven randomised studies involving 542 breast cancer patients addressing this question. These studies used six different herbal remedies to treat the side effects of chemotherapy, all used CMH plus chemotherapy as the intervention compared with chemotherapy alone. The results suggest that using Chinese herbs in conjunction with chemotherapy or CHM alone may be beneficial in terms of improvement in marrow suppression and Immune sytstem, and may improve overall state of quality of life. However, further trials are needed before the effects of TCM for people with breast cancer can be evaluated with any real confidence.There was no evidence of any harms of CMH.
We searched scientific databases for studies assessing the pain-relieving effects of intravenous (given into the blood stream through a vein) lidocaine in adults with a burn injury. We included studies comparing lidocaine with no treatment, placebo (a pretend treatment), other analgesics (pain killers), or a combination of these. We wanted to look at (for example) severity of pain, time to requiring more medication, rescue analgesia (where extra pain relief is needed in addition to that planned) and side effects. The evidence is current to December 2013. Key results We found one small clinical trial, involving only 45 participants, which showed a benefit from intravenous lidocaine for pain relief in people with burns. The trial did not show a difference in opioid use, participant anxiety or level of participant satisfaction with the use of intravenous lidocaine. Quality of the evidence The small included study provided insufficient data to draw any conclusions.
The review found 15 high quality trials of non-steroid drugs tested in idiopathic pulmonary fibrosis patients. Notwithstanding the encouraging results of a first small study included in the first version of this review, the effects of interferon gamma-1beta, as assessed by combining two subsequent large trials, were disappointing and failed to show an effect on improving survival. Four studies did evaluate pirfenidone, an anti-fibrotic oral drug, on a large number of patients: although two of these studies have only been presented in conferences,combining the published and unpublished data showed a significant improvement of pirfenidone on progression-free survival and a small increase in pulmonary function. Current evidence suggests a possible role for pirfenidone in the treatment of idiopathic pulmonary fibrosis, though data on survival are now needed. However, trials with other non-steroid agents are currently ongoing and new evidence may become available soon.
In our systematic review we could not identify substantial differences in the safety and efficacy between insulin species. Many important patient-oriented outcomes like health-related quality of life and effects on diabetic complications and mortality were never investigated. Human insulin was introduced into the market without scientific proof of advantage over existing purified animal insulins, especially porcine insulin.
Three randomised controlled studies were identified. Overall the quality of the evidence from these studies was moderate. They were reported on between 1977 and 1991 and involved a total of 309 participants. Each reported on different comparisons. Below knee amputation using skew flaps or sagittal flaps provided no advantage over the long posterior flap technique on primary stump healing, which approached 60% for all groups. In the third study, involving 30 participants with wet gangrene, a two-stage procedure with a guillotine amputation at the ankle followed by long posterior flap amputation led to better primary stump healing than a one-stage procedure with delayed skin closure. Post-operative infection rate or wound necrosis, reamputation and mobility with a prosthetic limb were similar in the different comparisons. Nearly all the surgeons in the study that looked at skew flap amputation versus the long posterior flap technique were new to the skew flap operation and so were on a learning curve. Factors which might have influenced the findings include previous experience of a technique, the extent of non-viable tissue, and location of pre-existing surgical scars.
We found two randomised controlled trials. Both studies compared plasma exchange with sham exchange (in which blood was removed and returned but not exchanged). One trial aimed to compare four weeks' plasma exchange with sham exchange. The 18 participants received both treatments, being randomised to either treatment in the first period of the trial, crossing over to the other treatment for the second period. The other trial compared three-weeks' plasma exchange in 15 participants with sham exchange in 14 participants. We considered both trials at low risk of bias, which means largely free of flaws that could have influenced the results. A charitable grant supported the cross-over trial. The other did not report any support. The cross-over trial showed on average two points more improvement on an 11-point disability scale with plasma exchange than sham exchange. This was unlikely to have occurred by chance. The parallel-group trial did not report this outcome. When we combined the results of both trials, plasma exchange produced significantly more improvement in severity of disease signs measured by neurologists than sham exchange. The results reported were short term. In practice, people with CIDP receive repeated courses or combinations of plasma exchange with additional agents. Another Cochrane review includes a trial showing similar improvement after plasma exchange to that after intravenous infusion of immunoglobulin (the antibody portion of blood). According to non-randomised evidence, plasma exchange causes adverse events in 3% to 17% of procedures. These are sometimes serious. Because of the small size of the only trial reporting changes in disability, the quality of the evidence that plasma exchange reduces disability is moderate. The quality of the evidence that plasma exchange improves the signs of disease measured by a neurologist is high. The evidence is up to date to 30 June 2015.
The evidence is current to February 2019. We found three studies that included 3851 participants. Two studies took place in the US and one study in the UK. One study tested whether delirium could be prevented by calculating how much fluid an older person in a care home needs each day and ensuring hydration was maintained. There were 98 people in the study, which lasted four weeks. One study tested the effect of a computer program which searched for prescriptions of medications that might increase the chance of developing delirium, to enable a pharmacist to adjust or stop them. There were 3538 people in the study, which lasted 12 months. One study tested an enhanced educational intervention which included learning sessions on delirium with care home staff and group meetings to identity targets for preventing delirium. There were 215 people in the study, which lasted 16 months. It was not possible to determine if the hydration intervention reduced the occurrence of delirium. This was a small study of short duration with serious design problems. The study of a computerised medication search programme probably reduced delirium, but there was no clear reduction in hospital admissions, deaths or falls. A potential problem is that it might not be possible to use this computer program in different countries that do not have similar computer systems available. It was not possible to determine if the enhanced education intervention reduced the occurrence of delirium and there was no clear reduction in the number of deaths. The intervention was probably associated with a reduction in hospital admissions. This is based on findings from a small study. There is very low-quality evidence on the effectiveness of hydration interventions for reducing the incidence of delirium. Therefore, it was not possible to draw firm conclusions. There is moderate-quality evidence that a computerised medication search programme may reduce the incidence of delirium. There is no clear evidence for reducing hospitalisations, mortality or falls. There is very low-quality evidence of the effectiveness of an enhanced educational intervention for reducing delirium. Therefore, it was not possible to draw firm conclusions. There is moderate-quality evidence for reducing hospital admissions. As this review only found a small number of research studies, we recommend that further research be conducted, testing different ways of preventing delirium for older people in LTC.
We searched for studies up to September 2016. We found 15 studies that provided the information we were looking for in conducting this review. A total of 3062 people had taken part in these studies; 2602 people took part in 11 studies looking at PAAP versus no PAAP, and 460 people were included in four studies looking at PAAP and education versus just education. Fourteen studies lasted six months or longer. The average age of people in these studies ranged from 22 to 49 years. Asthma severity ranged from mild to severe. We were able to use data from 10 of these 15 studies to inform our findings. PAAP alone compared with no PAAP: People using a PAAP did not show any difference (good or bad) in terms of having to go to the hospital because their asthma worsened compared with people not using a PAAP. This result was the same for changes in asthma symptom scores and number of deaths due to asthma. People with a PAAP showed no improvement in their quality of life compared with those without a PAAP, but the difference was not large enough to be meaningful. PAAP plus education compared with education alone: Review authors found no real difference - good or bad - between people using a PAAP and education and those just receiving education. This finding was the same for all outcomes, that is, having to go to the hospital because their asthma worsened and changes in symptom scores and quality of life. We rated the quality of the 15 included studies as low or very low because the few studies included in this review had problems with study design, including how to enrol people into the study and how to handle missing data for some people. Also, studies had problems with how outcome data for those who did not finish the study should be managed. This means that as future studies are completed and added to future versions of this review, the findings of the review may change.
In this update of a review originally published in 2001, we included a total of 25 studies (with a total of 6293 people) undertaken in a number of different countries. A variety of outcomes were assessed, including return of the hernia after initial repair (hernia recurrence), a variety of complications including pain, duration of surgery, hospital stay and time before going back to normal activities. One hernia recurrence is prevented for every 46 mesh repairs performed rather than non-mesh repairs. Compared to non-mesh repairs, mesh repairs are more likely to develop collections of fluid next to the surgical wound, but are less likely to result in difficulty urinating following the operation, or injury to nerves, blood vessels or other organs. Postoperative pain could not be clearly compared between studies due to differences in measurement methods and time frames, but overall the studies appeared to indicate that participants who had mesh repairs had less pain. The length of the surgical operation was slightly shorter for mesh repairs. Participants who had a mesh repair were more likely to have a shorter hospital stay and had a shorter average recovery time before returning to their normal activities. The studies included in this review used good-quality methods, considered potential factors which could affect the results, and addressed their proposed outcomes clearly. In our assessment of the quality of evidence, we marked down some outcomes to 'moderate' quality, particularly due to variability within results. Overall, hernia repairs with and without mesh both proved effective in the treatment of hernias, although mesh repairs demonstrated fewer hernia recurrences, a shorter operation time and faster return to normal activities. Non-mesh repairs are still widely used, often due to the cost and poor availability of the mesh product itself.
This review suggests the intra aortic balloon pump may be beneficial in terms of survival from the operation however there are many problems with the validity of the trials used in this review and a categorical answer to this question requires further randomised controlled trials.
We searched for randomised controlled trials (trials where treatment is allocated to women in a random manner) and well-designed non-randomised studies that compared different treatments in women aged 18 years or older with biopsy-confirmed Paget's disease of the vulva. We searched scientific databases and contacted experts and identified and checked the titles and abstracts of 635 possibly relevant articles and retrieved 31 of these references in full text. However, we found no studies that met our inclusion criteria. We identified several non-randomised studies and drafted a detailed narrative of their results, but these studies were of poor quality and were at high risk of bias. Therefore, there is currently no evidence to determine whether any form of treatment is better or worse in terms of prolonging survival, delaying progression or recurrence, improving QoL or minimising toxicity. The review highlights the need for good-quality studies comparing different interventions for the management of Paget's disease of the vulva. Women and clinicians would value more evidence for guiding surgical and non-surgical management of this disease. In particular, non-invasive medical management would spare women from the side effects and consequences of surgery.
This review investigates the effects of brief family intervention for people with schizophrenia, compared to standard or usual care. A search of the Cochrane Schizophrenia Group's trial register was carried out in July 2012. Four randomised studies, with a total of 163 participants were included. Results were limited, so it is not clear if brief family intervention reduces admission to hospital, decreases people using health services and reduces relapse for people with schizophrenia. The review found some evidence that brief family intervention might increase the understanding of family members about mental illness. However, all main findings are not strong and based on low or very low quality evidence. Despite this, the authors of the review suggest that brief family intervention should not be completely dismissed, as it is in a current state of demand and there are usually resources or local services available for people with mental health problems and their families to participate in as a part of recovery. The authors also suggest that brief family intervention could be improved to be more effective but this would depend on larger and better studies of brief family intervention being carried out, which would help guide good practice and lead to better outcomes for people with schizophrenia. This plain language summary has been written by a consumer, Ben Gray, from RETHINK.
In our study we assessed the different techniques used for resealing the waters. We aimed to compare the survival of babies affected with this condition before and after birth and look at the rates of complications in both the babies and mothers. We searched for trials (30 May 2016) and found two studies that compared treatments for resealing the membranes after they had broken. These trials involved 141 women in total and compared two completely different modes of treatment. One trial compared the use of an oral immunological membrane sealant to stimulate the body’s immune system to mend the area where the seal has broken and the other trial placed a mechanical sealing device over the cervix (neck of the womb) to stop fluid leaking. Unfortunately, neither trial provided any data relating to death of the baby within the womb or in the first 28 days of life (perinatal mortality). There was limited evidence to suggest that oral immunological membrane sealant was associated with a fewer babies being before 37 weeks’ gestation and a reduction in the number of babies that died within the first 28 days. However, these results are based on very low-quality evidence from one small trial (with data from 94 women) that we judged to be at a high risk of bias. There was no clear difference between the mechanical sealing device group and the control group in relation to the number of babies who contracted a serious infection (neonatal sepsis) or chorioamnionitis (a bacterial infection that causes inflammation of the membranes surrounding the baby in the womb). Although these results are based on very low-quality evidence from one small trial (involving 35 women) judged to be at a high risk of bias. Overall, our question remains unanswered - we do not have enough data to fully evaluate sealing procedures for PPROM. This review demonstrates the lack of research in this area regarding the effectiveness and safety of potential treatments for PPROM. We recommend that more research is needed to look at the different techniques for sealing broken waters and that this research should focus on the effectiveness of the treatment in improving overall outcomes. The safety of the treatments to both mother and baby must be further evaluated before sealing techniques can be recommended to prevent adverse outcomes.
The two studies included in this review looked at using LMWH with 5-FU during retinal detachment repair to see if there was an effect of reducing PVR levels after surgery. One study focused on patients who are considered at high-risk of developing PVR after surgery because of pre-existing ocular features, and found beneficial effects of this treatment in this group. The other study looked at a wider group of patients and did not find a benefit in using this combination treatment, and in certain patients the treatment was associated with poorer vision. Due to the inconsistency of the evidence, until further data are available, future research on the use of LMWH with 5-FU should be conducted only in retinal detachment patients who are likely to develop considerable retinal scarring after surgery.
More than 1000 infants have been enrolled in trials of ibuprofen for prevention of a PDA; most studies were of small sample size. Prophylactic use of ibuprofen reduces the incidence of patent ductus arteriosus (PDA), the need for rescue treatment with other medications, or the need for surgical closure. Adverse effects in the ibuprofen group compared to the placebo or no interventions group included significantly increased risk of kidney complications. Risk of digestive tract bleeding was increased with ibuprofen. Risk of intraventricular haemorrhage, or bleeding into the brain (grade II to IV), of borderline significance was reduced, but researchers reported no statistically significant differences in mortality, chronic lung disease at 28 days' or 36 weeks' postmenstrual age, necrotising enterocolitis, or time to reach full feeds. In the control group, the PDA had closed spontaneously by day 3 or 4 in 58% of neonates. Preventative treatment therefore exposes a large proportion of infants unnecessarily to a drug that has important side effects without conferring any important short-term benefit for outcomes. No long-term follow-up studies have been published. Current evidence does not support the use of ibuprofen for prevention of PDA. A new approach for management of PDA is an early targeted treatment based on echocardiographic (ECG), or image of the heart, criteria within the first 72 hours of life; this has high sensitivity for diagnosing a PDA that is unlikely to close spontaneously. Such trials are currently ongoing in many parts of the world. This updated review of trials found that ibuprofen can prevent PDA but does not confer any other short-term or long-term benefits. The quality of evidence varied from low to high for different outcomes.
We included eight small randomised trials involving 282 people. The trials presented results for a total of 248 people with chronic osteomyelitis. Post-traumatic bone infections were the most frequent type. Surgical removal of the infected tissue (debridement) before starting on antibiotic therapy was mentioned as part of treatment in all trials, but in four trials it was unclear whether all participants underwent surgery. There were five comparisons of different treatments but we could only pool results for the comparison of antibiotic given by mouth with antibiotic given parenterally. The pooled results (which included data from 150 people) did not show any difference between people given antibiotics by mouth or parenterally in terms of the number of people who did not have symptoms (in 'remission') at the end of treatment (four trials) or 12 months later (or more) (three trials); nor in the number of people that had negative side effects or had a superinfection (another infection that is not sensitive to antibiotic treatment). This evidence suggests that the way antibiotics are given does not impact on the disease remission rate if the bacteria causing the infection are sensitive to the antibiotic used. However, confirmation is needed. There was either no or insufficient evidence on which to base judgements about the optimum length of antibiotic treatment or the best antibiotics to use.
The evidence is current to 2 October 2017. We included seven studies that randomly allocated a total of 581 participants with stable angina to either receive cardiac rehabilitation or no exercise control. We identified that there are no ongoing randomised studies. The average age of participants ranged from 50 to 66 years. The majority of people recruited were middle-aged men. Most studies were carried out in European countries and one study in India. Cardiac rehabilitation was most commonly delivered in a combined setting of home and centre or hospital. The length of the cardiac rehabilitation programmes ranged from six weeks to one year. There is insufficient evidence to assess the impact of exercise-based cardiac rehabilitation on the outcomes that matter most to patients: risks of death, heart attack, or future cardiac operation and quality of life. There may be a small improvement in physical fitness following exercise-based cardiac rehabilitation compared to usual treatment. There was no evidence about returning to work. Due to the poor reporting, high risk of bias and small number of trials and participants included in this review, our assessment of the quality of the evidence ranged from low to very low across outcomes. For low-quality evidence our confidence in the result is limited, and for very low-quality evidence we have very little confidence in the result. We need more high-quality studies in more representative populations of people with stable angina. These studies should collect outcomes of relevance to patients and healthcare decision-makers. Then we will be able to better assess the impact of exercise-based cardiac rehabilitation.
We searched scientific databases for studies that looked at the effects of milnacipran in adults with fibromyalgia who had moderate or severe pain. The treatment had to last at least eight weeks. The evidence is current to May 2015. We identified six studies that satisfied the inclusion criteria, including one new study for this update. Over 4000 participants were treated with milnacipran 100 or 200 mg, or placebo, for 8 to 24 weeks at the target dose. Overall study quality was good, although the method of analysis for our primary outcomes of pain relief could overestimate treatment effect. Milnacipran at either dose provided moderate pain relief (at least 30% reduction in pain intensity) to 1 in 10 (10%) more people than did placebo (high quality evidence). This relatively modest effect may be clinically important in this difficult-to-treat condition. Adverse events were reported by most participants in all treatment groups, but were more common with milnacipran than placebo (high quality evidence), with nausea (feeling sick) and constipation showing the greatest differences (moderate quality evidence). Serious adverse events were uncommon, fewer than 1 in 50 (2%) participants, and did not differ between treatment groups (low quality evidence). The numbers of participants dropping out of the studies (withdrawals) because of adverse events were also more common with milnacipran than placebo, and were more common with 200 mg than 100 mg (high quality evidence), while withdrawals due to lack of effect were less common with milnacipran, with no difference between doses (moderate quality evidence). Milnacipran gives good pain relief to some people with fibromyalgia, but only a minority; it will not work for most people.
This meta-analysis of eleven randomised clinical trials could not find sufficient evidence to support or refute the use of antibiotic prophylaxis to reduce surgical site infection or global infections in patients with low anaesthetic risk, low co-morbidities, and low-risk of conversion to open surgery, and undergoing elective laparoscopic cholecystectomy. This is why large and well-designed randomised trials including patients with high-risk of conversion to open surgery should be conducted in order to define the beneficial or harmful effects of the antibiotics when given as a prophylaxis.
We used clinical trials to see if treatment of H pylori-positive Parkinson's disease patients with antibiotics improved the absorption of levodopa and improved their motor symptoms. Only two completed trials were found from our searching. We did not pool these as they had different objectives and used different outcome measures. One of the trials reported a significant increase in levodopa absorption and improvement in motor symptoms when antibiotics were used to eradicate H pylori. The other completed trial did not have any usable results. A further trial of H pylori eradication in Parkinson's disease is still underway and the results, which are due in 2010, will help inform further studies. Very little information was found about H pylori eradication in Parkinson's disease. More clinical trials are needed using standard measures of motor symptoms. It will be important also to look at the cost of both screening for H pylori and treatment of H pylori in Parkinson's disease patients to see if this is worthwhile.
The review authors searched the medical literature for studies that evaluated mental and motor development in infants and children randomly assigned to receive either zinc supplements or a 'placebo' (fake) supplement. We found 13 relevant studies. Eight studies measured development using the Mental Development Index and the Psychomotor Development Index of the Bayley Scales of Infant Development. We found no difference between the results for those who had taken zinc supplements and those who had taken a placebo. Two studies measured children's attainment of motor milestones. Again, no difference as found whether zinc supplements were taken or not. No study measured possible side effects of zinc supplementation such as vomiting, diarrhea or anemia. Overall, the results of the studies provided no convincing evidence that zinc supplements had any beneficial effect on mental and motor development in infants and children.
This review update added three new studies including 419 participants to the review. We performed the most recent searches in March 2016. In total, we found eight studies involving 1669 people with mild or moderate asthma. Three were conducted in children, and five in adults. These studies provided participants with an inhaler that contained extra doses of ICS (to increase their usual ICS dose) or a placebo that could be used if their symptoms worsened. Participants were then followed for six months to one year to see whether people taking more inhaled corticosteroids during attacks did better than those who took a placebo. People taking an increased dose of ICS during an attack did not do better than those who took a placebo, regardless of whether we looked at all study participants or only those who actually took the inhalers during an attack. Results showed a lot of variation in studies that focused only on people who took the inhalers, with some studies showing benefit of increasing ICS dose and others showing no benefit. It is unlikely that increasing ICS dose reduces the need for a course of oral steroids to treat the attack, prevents the need for an emergency visit with doctors or at the hospital or reduces the time it takes to recover. We cannot be sure of these last results because few studies reported them. Use of either strategy was not associated with significantly more or less serious and non-serious side effects, but again we cannot say for sure because we did not find enough studies. We have rated results of this review as having moderate or low quality, depending on the outcome. This means that some of the findings were very uncertain, mainly because the studies included very few people who could say definitively whether increasing the dose was better or worse than, or no different from, keeping the dose stable.
In the present Cochrane systematic review, we set out to assess the benefits and harms of fibrinogen concentrate in patients with bleeding. We searched the databases to August 2013, we identified six randomized trials in cardiac and elective surgical settings that compared fibrinogen concentrate (248 participants) with placebo/other sources or no treatment. Additionally, we found 12 ongoing trials, but we were unable to retrieve any data from them. We could not identify beneficial effects of fibrinogen concentrate on patient survival. In our predefined outcomes, we identified a reduced proportion of patients requiring donor blood transfusion. We could not identify reduced blood loss or any harms or adverse events caused by treatment with fibrinogen concentrate. However, all trials were of low quality and were small, so evidence in support of fibrinogen concentrate in patients with bleeding remains weak.
The review of four small trials found that there was no large difference between the drugs in the short term. There is not enough evidence to exclude a small difference in benefit, long term effects or a difference in less common adverse effects. More research is needed into the long term and adverse effects of these drugs.
To date, approximately 5000 infants have been enrolled in studies conducted to evaluate the effects of prophylactic use of intravenous immunoglobulin on neonatal outcomes. Intravenous administration of immunoglobulin results in a 3% reduction in blood-borne infection and a 4% reduction in serious infection. Intravenous administration of immunoglobulin is not associated with reductions in other important neonatal outcomes or in length of hospital stay. Most important, intravenous immunoglobulin administration does not have any important effect on mortality. Prophylactic use of IVIG is not associated with any short-term serious side effects. From a clinical perspective, a 3% to 4% reduction in nosocomial infection without a reduction in mortality or other important clinical outcomes is of marginal importance.
The majority of the trials compared two different types of omega 3 fatty acids, EPA (usually as E-EPA) and DHA with placebo, in people with schizophrenia who are stable on antipsychotic medication. Some of these trials show some improvement in general functioning and in mental state but not to a statistically significant degree. In the longest trial there was no difference between the two groups at the end of the study.  One trial compared E-EPA with DHA and found a suggestion that E-EPA works better than DHA, but again it was not statistically significant.  Where EPA was compared to placebo as a first line treatment for schizophrenia (30 people), those taking EPA had a better overall outcome and improvement in mental state.  However, this was a short trial with few people. Finally, one trial compared a type of omega 6 with placebo in men who had the movement disorder tardive dykinesia (16 people). There was no improvement in the symptoms of movement adverse effects in either group at the end of six weeks. These trials were both small and short.  In addition most of the data they reported were not able to be used, and half of the trials were funded by the group supplying the trial medication. Therefore it is still not clear whether taking manufactured omega 3 or 6 improves overall functioning or mental state in people with schizophrenia. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org)
The non-reporting of a piece of research and the selective reporting of only some of its findings has been identified as a problem for research studies such as randomised trials and systematic reviews of these. If the decision about what to report and what to keep unpublished is based on the results obtained in the trial, this will lead to bias and potentially misleading conclusions by users of the research. One way to see if there might be discrepancies between what was planned or done in a trial and what is eventually reported is to compare the protocol or entry in a trial registry for the trial with the content of its published report. This might reveal that changes were made between the registration and planning of the trial and its eventual analysis. Any such changes should be described in the published report, to reassure readers and others who will use the trial's results that the risk of bias has been kept low. This Cochrane methodology review examines the reporting of randomised trials by reviewing research done by others in which the information in protocols or trial registry entries were compared to that in the published reports for groups of trials, to see if this detected any inconsistencies for any aspects of the trials. We included 16 studies in this review and the results indicate that there are often discrepancies between the information provided in protocol and trial registry entries and that contained in the published reports for randomised trials. These discrepancies cover many aspects of the trials and are not explained or stated in the published reports.
We performed this systematic review to investigate the beneficial and harmful effects of weight reduction with different measures for NAFLD patients, but we could not find firm evidence. Five trials on lifestyle programme and two trials on orlistat were obtained, and all but one had high risk of bias. There seemed to be some beneficial effects of lifestyle programme involving restricted diet and physical exercise for NAFLD patients. However, the data were sparse, and meta-analyses could not be performed. Well-designed randomised clinical trials are needed to establish the true effect of the weight reduction measures identified for our review. The long-term prognosis of development of fibrosis, mortality, and quality of life modified by weight reduction should be studied. Special attention should be paid to the amount of weight loss.
In this review, we included five randomised controlled trials, with a total of 265 participants. All participants had Ménière's disease and their ages ranged from 19 to 74 years. In all of the studies positive pressure therapy was compared with a placebo device. For our primary outcome, control of vertigo, we could not combine the results from the different studies because of differences in the way the outcome was measured. None of the included studies showed significant differences between the active groups and placebo groups in terms of vertigo days. Only one study found significantly lower subjective scores for vertigo in favour of the positive pressure therapy group when compared to the placebo group. When we combined the results from two studies we found that after treatment patients in the placebo group had better hearing levels compared to those in the positive pressure therapy group. The severity of tinnitus and perception of aural fullness were either not measured or the included studies did not provide enough information for us to comment on them. We did not find an overall statistically significant result for functional level. We also looked at 'sick days' but we did not find a statistically significant difference between groups in the two studies that measured this. No complications or adverse effects were noted by any study. Overall, the studies were at varied risk of bias: three out of five studies were at low risk, one was at unclear risk and one was at high risk of bias. The evidence is up to date to June 2014. In conclusion, this review has not found adequate evidence to prove the effectiveness of positive pressure therapy. Further research is needed.
The available experimental studies did not demonstrate the effectiveness of AA or other 12-step approaches in reducing alcohol use and achieving abstinence compared with other treatments, but there were some limitations with these studies. Furthermore, many different interventions were often compared in the same study and too many hypotheses were tested at the same time to identify factors which determine treatment success.
We found 12 studies of corticosteroid treatment in DMD, involving a total of 667 randomised boys; two other studies are ongoing. Among the 12 completed studies, the treatments were: a corticosteroid versus inactive medicine (placebo) (in nine trials); daily versus weekend-only prednisone (in one trial); and deflazacort versus prednisone (in three trials). Some studies included more than one comparison; some were not fully reported or provided results that could not be analysed. One trial, a two-year study comparing a corticosteroid (deflazacort) with placebo, assessed the effects of corticosteroids on the ability to continue walking, but the data were not suitable for analysis. Most studies did not report ability to continue walking. At the usual 0.75 mg/kg/day dose, corticosteroids improved muscle strength and function over six months compared to placebo. These results are based on combined data (up to 152 participants) from four trials, which provided moderate quality evidence. Improvements were seen in timed tests (eg. timed walk or run, time to stand, stair climb), ability to lift weights, a leg function grade, and a measure of the strength of muscles used in breathing. Evidence from single trials showed 0.75 mg/kg/day prednisone to be superior to 0.3 mg/kg/day on most strength and function tests, with little evidence of greater benefit at 1.5 mg/kg/day. Changes in appearance and hair growth were more common at 0.75 mg/kg/day than 0.3 mg/kg/day. One RCT (n = 66) also reported better strength, function and quality of life at 12 months with daily 0.75 mg/kg/day prednisone. The two-year RCT, which had 28 participants, showed that deflazacort stabilised muscle strength for up to two years compared to placebo. This study did not show benefit on timed tests at two years; however, these results are imprecise and at high risk of bias, with less than half the original participants contributing data. One trial found that changes in muscle strength and function were similar with daily and weekend-only prednisone regimens over a 12-month period (low to moderate quality evidence). Two small RCTs compared daily prednisone 0.75 mg/kg/day with daily deflazacort 0.9 mg/kg/day, but trial methods did not allow comparisons of muscle strength or function. Previous versions of this review have found adverse events such as excessive weight gain, abnormal behaviour, changes in appearance, and abnormal hair growth to be more common with corticosteroids than with placebo. We assessed the quality of evidence for abnormal behaviour and weight gain for this review and found it to be moderate. The newer study of daily versus weekend-only prednisone showed that both groups gained weight. The body mass index (BMI; a measure of weight for height) did not show any clear difference between the regimens (low quality evidence). The weekend-only group had a greater increase in height. According to very low quality evidence from two studies, deflazacort appeared to cause less weight gain at one year than prednisone, and no significant difference in numbers with behaviour change. Data were insufficient to assess the risk of fractures or cataracts. The evidence is up to date to February 2016.
This review of 28 trials, involving 5855 participants, showed that patients who receive this care are more likely to survive their stroke, return home and become independent in looking after themselves. A variety of different types of stroke unit have been developed. The best results appear to come from those which are based in a dedicated ward.
The review of trials found that the type of homeopathy varied between the studies, that the study designs used in the trials were varied and that no strong evidence existed that usual forms of homeopathy for asthma are effective. There has been only a limited attempt to measure a 'package of care' effect (i.e., the effect of the medication as well as the consultation, which is considered a vital part of individualised homeopathic practice). Until stronger evidence exists for the use of homeopathy in the treatment of asthma, we are unable to make recommendations about homeopathic treatment.
Based on an electronic search carried out in 2012, this review now includes seven studies that randomised a total of 1113 people with serious mental illness. Six studies compared general physical health advice with standard care, one compared advice on healthy living with artistic techniques such as sketching and pottery. Information was of limited low or very low quality, there were a small number of participants and findings were ambiguous. There is some limited evidence that the provision of physical healthcare advice can improve health-related quality of life mentally but not physically. No studies returned results that suggest that physical healthcare advice has a powerful effect on physical healthcare behaviour or risk of ill health. More work is needed in this area. Only one adverse effect outcome was presented, death, but there were no differences between the treatment groups for this outcome. Funders and policy makers should be aware that there may be some benefit for physical health advice for people with serious mental illness. There is an increased demand for preventative health services that involve the provision of advice and which may also reduce costs to health services. This plain language summary has been written by a consumer, Ben Gray from RETHINK.
Cabergoline has been compared with the older agonist bromocriptine in five studies including 1071 patients. Only one of the smaller studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The time patients spent in the immobile off state was reduced with both agonists but slightly more by cabergoline compared with bromocriptine. This small advantage of cabergoline did not reach statistical significance. Dyskinesia reported as a side effect was significantly increased with cabergoline compared with bromocriptine. Physical impairment and disability were measured in four of the studies but no statistically significant advantage for cabergoline was found. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was significantly more confusion with cabergoline. Otherwise, dopaminergic side effects were comparable with these agonists and no significant difference in the withdrawal rate from the trials was found. Cabergoline produces similar benefits to bromocriptine in off time reduction, physical impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. The frequency of side effects and withdrawals from treatment were similar with the two agonists apart from increased dyskinesia and confusion with cabergoline.
The studies included in this review took place in Africa and India. In five of the studies, people were either given insecticide-treated bednets free, or could buy them at a subsidized price or full market price. In the other five studies, people were educated about how to use the bednets properly, for instance through visits at home or through information on the radio, on television and in the community. The included studies show the following: Providing free insecticide-treated bednets: - Probably increases the number of people who own bednets compared to providing subsidized bednets or bednets offered at full market price. - Probably leads to little or no difference in the use of bednets compared to providing subsidized bednets or bednets offered at full market price. Providing education for the appropriate use of insecticide- treated bednets: - May increase the number of adults and children under five using bednets (sleeping under bednets). Providing incentives to encourage use of insecticide-treated bednets: - Probably leads to little or no difference in ownership or use of bednets compared to those who did not receive an incentive. A possible side effect when providing free or subsidized insecticide-treated bednets may be that the governments and institutions who pay for the bednets take this money from other priority issues. However, none of the included studies measured whether these or any other side effects had occurred.
This review identified four controlled trials involving 127,891 men and 9342 women who were randomly assigned to aortic aneurysm screening using ultrasound or no screening. Only one trial included women. Two of the trials were conducted in the UK, one in Denmark and one in Australia. The results provide evidence of a benefit from screening in men with a strongly significant reduction in deaths from abdominal aortic aneurysm. The odds ratio (OR) for death was 0.60 (range 0.47 to 0.78, three trials) in men aged 65 to 83 years but was not reduced for women. From one trial there was also a decreased incidence of ruptured aneurysm in men but not women. All-cause mortality was not significantly different between screened and unscreened groups some three to five years after screening, which is to be expected given the relative infrequency of abdominal aortic aneurysm as a cause of death. Men who had been screened underwent more surgery for abdominal aortic aneurysm (OR 2.03; range 1.59 to 2.59, four trials) but resource analysis appears to demonstrate overall cost effectiveness of screening. There were no data on life expectancy, complications of surgery or quality of life.
We identified five studies that evaluated effects of sildenafil: three studies that compared sildenafil with placebo (no sildenafil); one that compared sildenafil with other medication (magnesium sulphate); and one that used sildenafil in combination with another medicine (nitric oxide). These studies included 166 newborns and were conducted in Colombia, Mexico, Turkey, and Qatar. Three studies that compared sildenafil and placebo (no sildenafil) reported that sildenafil reduced the number of deaths. Studies that compared sildenafil against another medication or that used another treatment with sildenafil described no significant reduction in the number of deaths. Sildenafil was more effective than placebo in improving oxygen levels. None of the five included studies reported safety concerns. However, these studies enrolled small numbers of infants, and most were conducted in settings where other treatments were not available. Sildenafil may be useful in settings where other treatment approaches are not available. However, additional studies are needed to compare sildenafil against existing treatment in a resourceful environment to assess its effectiveness and safety. The quality of evidence for reducing mortality or improving respiratory parameters was low owing to the small number of included studies and the small number of babies evaluated. Some of the included studies have methodological issues, resulting in low to very low quality of evidence.
We conducted a search for relevant clinical trials in February 2017. We included six studies of manual acupuncture: one compared acupuncture with sham acupuncture; three investigated acupuncture combined with other active treatments compared with other active treatments alone; two compared acupuncture alone compared with other active treatments. The six studies involved 462 adults with chronic peripheral neuropathic pain. The participants were 52 to 63 years of age, on average. They received treatment for eight weeks or more. We did not find any study comparing acupuncture with treatment as usual, nor any study of other acupuncture techniques (such as electroacupuncture, warm needling, fire needling). We are uncertain about the beneficial effects of manual acupuncture on pain intensity, pain relief and quality of life when compared to sham acupuncture or other therapies (such as mecobalamin, nimodipine, inositol, and Xiaoke bitong capsule). There is a lack of evidence on the potential harms (side effects) of acupuncture. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The quality of the evidence in this review is very low, mostly due to problems in the way the studies were conducted (such as the participants were not blinded to their treatment, or more participants in the sham acupuncture group left the study early). The studies also included a small number of participants. Moreover, these findings only apply to peripheral neuropathic pain in older adults. Overall, we do not have sufficient evidence to support or refute the use of acupuncture in treating neuropathic pain.
Following our data search in January 2018, we included 10 trials with a total of 844 participants, which we assessed using the standard Cochrane Review protocol. The trials compared the incidence of hernia development around a stoma between a group having a mesh placement at the time of stoma formation and a control group having a conventional stoma formation without mesh placement. We found that mesh placement around the stoma at the time of stoma formation reduces the incidence of future hernia formation. The participants having a mesh fitted had a similar level of complications as those not having a mesh. We found low-quality evidence favouring the insertion of a mesh into people having a stoma.
This review found that exercise improves blood sugar control and that this effect is evident even without weight loss. Furthermore, exercise decreases body fat content, thus the failure to lose weight with exercise programmes is probably explained by the conversion of fat to muscle. Exercise improved the body's reaction to insulin and decreased blood lipids. Quality of life was only assessed in one study, which found no difference between the two groups. No significant difference was found between groups in blood levels of cholesterol or blood pressure. A total of 14 randomised controlled trials were assessed. These included 377 participants and compared groups that differed only with respect to an exercise programme intervention. The duration of the interventions in the studies ranged from eight weeks to one year. Two studies reported follow-up information, one at six months after the end of the six month exercise intervention and one at twelve months post-intervention. Generally, the studies were well-conducted, but blinding of outcome assessors was not reported and although all studies reported that randomisation was performed, few gave details of the method.   No adverse effects with exercise were reported. The effect of exercise on diabetic complications was not assessed in any of the studies. The relatively short duration of trials prevented the reporting of any significant long term complications or mortality. Another limitation was the small number of participants included in the analyses for adiposity, blood pressure, cholesterol, body's muscle and quality of life.
We included two studies involving 147 adults with acute sinusitis. Participants were randomly allocated to receive Cyclamen europaeum delivered as an intranasal spray or a non-active substance for up to 15 days. Pharmaceutical companies funded both studies. We wanted to find out the proportion of participants whose symptoms resolved or improved up to 14 days and 30 days, but did not find any evidence. The included studies provided data for changes in symptom scores for acute sinusitis with treatment. One study reported improvement in facial pain up to seven days. Neither study reported complications or days off school or work. People who received Cyclamen europaeum rather than a non-active substance reported more side effects like nasal irritation, sneezing, and mild nasal bleeding. No major side effects occurred. We found no evidence as to whether Cyclamen europaeum is effective or not. We assessed the quality of both studies and judged the evidence to be moderately reliable for the only outcome that could be assessed, that is side effects. One study had a high dropout rate (60%), but dropouts were described and balanced between study arms. We found consistent results between studies for adverse events. Neither study reported whether the outcomes assessors knew which treatments the participants received. Due to the small number of participants and weaknesses in study design, we cannot be sure of the result.
Our findings are based on two large studies with 3375 participants and should be applicable to most women having treatment for DCIS. Overall tamoxifen did reduce the number of future cancers or DCIS in either breast. However, women taking tamoxifen did not live longer than those who did not take it. A total of 15 women would have to take tamoxifen after treatment of DCIS for one woman to experience a benefit (i.e. no future cancers or DCIS in either breast after taking tamoxifen for five years). There are side effects of tamoxifen treatment such as blood clotting problems (stroke, deep vein thrombosis, pulmonary embolism) and endometrial cancer. However, no risk/benefit conclusions are possible because there was limited information about the side effects in this review. The effects of tamoxifen may have been 'diluted' by the effects of radiotherapy. This review cannot recommend which women might have more benefit from using tamoxifen in terms of age, menopausal status or type of DCIS (oestrogen receptor (ER)-positive versus ER-negative or human epidermal growth factor receptor 2 (HER2)-positive or HER2-negative DCIS).
This systematic review included seven randomized clinical trials involving 632 eyes from five countries evaluating the effectiveness and safety of intravitreal steroids for treating DME. Two trials were at low risk of bias, one was at median risk of bias, two were at high risk of bias, and the remaining two had an unclear risk of bias. In this systematic review, the preponderance of data suggest a beneficial effect from IVTA. The average improvement in visual acuity was 7.5 letters more (-0.15 LogMAR; 95% CI -0.21 to -0.09) in the IVTA treated eyes than in those treated with other therapies at three months (based on three trials), 11.5 letters more (-0.23 LogMAR; 95% CI -0.33 to -0.13) at six months (two trials), 14.5 letters more (-0.29 LogMAR; 95% CI -0.47 to -0.11) at nine months (one trial), and 5.7 letters more (-0.11 LogMAR; 95% CI -0.20 to -0.03) at 24 months (one trial). Improved clinical outcomes were also reported in FAI and dexamethasone DDS trials. Elevation of intraocular pressure and cataract progression occur in both IVTA and implants treated eyes but appear manageable.
We included 12 randomized controlled trials (3885 participants) in our review. The studies included adults aged 48 to 70 years from surgical and medical ICUs. The studies compared different drugs (three studies) various approaches to sedation (five studies), physical or cognitive therapy or both (one study), noise and light reduction in the ICU (two studies), and preventive nursing care (one study). The studies had mostly small numbers of participants and did not blind the researchers who assessed effects on outcomes. We report the findings regarding the effect of the two most commonly explored approaches for preventing delirium, drug and non-drug interventions, haloperidol versus a sham drug, and early physical and cognitive therapy versus usual care. Our findings suggest that there may be little or no difference between haloperidol and placebo for preventing ICU delirium, but further studies are needed to reduce imprecision and increase our confidence in the findings. More studies of physical and cognitive therapy are needed as there is insufficient evidence to determine whether these non-pharmacological approaches can prevent delirium in the ICU. Additional research is required to explore the benefits and harms of other approaches to prevent delirium in the ICU such as sedation and changes in the ICU environment, and nursing care tailored to prevent delirium. We rated the quality of the evidence as moderate to very low. Several studies had quality shortcomings, including their use of small numbers of participants, and lack of blinding of those assessing effects of interventions for preventing delirium and other outcomes. For the interventions testing sedation approaches, physical and cognitive therapy, and changes in the environment, additional research is required to clarify their effectiveness. The five studies in ‘Studies awaiting classification’ and 15 ongoing studies may alter the conclusions of the review once they are completed and assessed.
We performed a thorough literature search for studies reporting the accuracy of drain fluid amylase in identifying pancreatic leaks. We included studies reported up to 20 February 2017. We identified five studies reporting information on 868 people who underwent pancreatic resections for cancer and non-cancerous growths. Most studies included only people in whom the head of the pancreas (right side of the pancreas) was removed. Variations in when the studies measured the amylase content in the drain and what level was considered abnormal meant that we were not able to combine the data to provide the overall results. We are uncertain whether drain fluid amylase is useful in identifying pancreatic leaks because of the following reasons. 1. The way that study authors confirmed that a participant had or did not have pancreatic leak was itself subject to error (i.e. there was no true 'gold standard'). 2. The studies included few participants. As a result, there was significant uncertainty in the results. 3. The studies were of poor methodological quality. This introduced additional uncertainty in the results. All of the studies were of unclear or low methodological quality, which may result in arriving at false conclusions.
The evidence is current to January 2017. We included 64 studies related to six different types of drugs recommended for HAI prevention. Most of the studies were conducted in high altitude mountain areas, while the rest used low pressure (hypobaric) chambers to simulate altitude exposure. The participants' ages ranged between 16 and 65 years. Eleven studies included people at a high risk of this condition due to their history of HAI or other illnesses such as asthma. Twenty-four trials provided the intervention between three and five days prior to the ascent, and 23 trials, between one and two days beforehand. Most of the included studies reached a final altitude of between 4001 and 5000 metres above sea level. In 23 of the included studies, the source of funding was unclear. Only 18 studies declared their possible conflicts of interests. We classed 24 more studies as still ongoing or waiting for assessment. Our findings suggest that acetazolamide is an effective treatment for the prevention of acute HAI in dosages of 250 to 750 mg/day, when this drug is compared to a placebo (i.e. a pill with no active agent). Most of the available information relates to the prevention of uncomplicated HAI (headache, nausea, vomiting and tiredness) rather than to more serious brain or lung problems. We also found that acetazolamide is associated with an increased risk of paraesthesia in the fingers (i.e. a sensation of tingling, tickling, pricking, or burning of the skin), although this outcome is not well reported in the available evidence. The benefits and harms of other drugs such as ibuprofen, budenoside and dexamethasone are unclear, due to the small number of studies. We rated the quality of the evidence as moderate to very low. Several studies had quality shortcomings, including their use of small numbers of participants and a lack of reporting of important outcomes such as side effects. For most of the drugs covered by the studies, additional research is required to clarify their effectiveness and safety.
We searched for clinical trials in which NSAIDs were used to treat symptoms of fibromyalgia in adults. The latest search was in January 2017. Six studies satisfied the inclusion criteria, randomising 292 participants to treatment with NSAID or placebo. NSAIDs tested were etoricoxib 90 mg daily, ibuprofen 2400 mg daily, naproxen 1000 mg daily, and tenoxicam 20 mg daily; 146 participants received NSAID and 146 placebo. Study duration was between three and eight weeks. Not all studies reported the outcomes of interest. We found no difference between NSAID or placebo for a range of outcomes. Pain reduction by half or better was experienced by 1 in 10 with NSAID and 2 in 10 with placebo. Pain reduction by a third or better was experienced by about 2 in 10 with both NSAID and placebo. Side effects were experienced by 3 in 10 with NSAID and 2 in 10 with placebo. The evidence was of very low quality. This means that the research does not provide a reliable indication of the likely effect. The chance that the real effect of NSAIDs could be substantially different is very high. Small studies like those in this review tend to overestimate results of treatment compared to the effects found in larger, better studies. The very low-quality evidence and the lack of any obvious benefit mean that NSAIDs cannot be regarded as useful for the management of fibromyalgia.
We found six studies comparing ciclesonide with either budesonide or fluticasone in 3256 children (aged four to 17 years) with chronic asthma. After three months of treatment with ciclesonide compared to budesonide or fluticasone, no relevant differences could be found on asthma symptoms, exacerbations or side effects. Ciclesonide compared to a double dose of fluticasone was assessed in one study and no differences were found in asthma symptoms, use of rescue medication and adverse effects. However, children receiving ciclesonide experienced more asthma exacerbations than children in the fluticasone group. The results of this review regarding the efficacy and safety of ciclesonide compared to other ICS are not conclusive. Relatively few studies were found, different inhalers were compared and treatment and follow-up time (12 weeks) was too short for the assessment of relevant outcomes such as exacerbations and growth retardation. Future studies should pay attention to those aspects.
In January and February 2013, we did computer searches to find randomized trials of combination injectable contraceptives. We included studies that compared a CIC with another birth control method. The other method could be another injectable contraceptive, either combined or having only a progestin. The CIC could also be compared to another hormonal method (like the pill) or to condoms, the diaphragm, or a placebo (or 'dummy'). We found 12 trials that studied four types of CICs. The combined methods required monthly injections. Four trials compared a CIC to 'depo', which has only a progestin. 'Depo' injections should be taken every three months. Five trials compared a CIC with a different combined injectable. Three trials compared a combined injectable with a different dose of the same hormones, with a progestin-only injectable, or with an intrauterine device (IUD). More women using combined injectables had normal bleeding than women using progestin-only injectables like 'depo.' Also, fewer women using CICs stopped using them because of bleeding reasons than progestin-only users. However, users of combined injectables were more likely to stop using them overall and to stop for other medical reasons. Many factors can affect whether women keep using the method, including whether the women liked it.
We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of vitamin K supplementation in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes). The evidence is current to September 2014. Only one small trial met our inclusion criteria. It included 60 participants aged 40 to 65 years. This study looked at the effects of vitamin K2 supplements on CVD risk factors (blood pressure and lipid levels) over three months in healthy participants. No differences in these risk factors were seen between the comparison groups, but this was a small study and the findings are limited. The trial did not look at fatal and non-fatal cardiovascular endpoints as it was small and short term. The evidence is currently extremely limited and further high-quality trials are needed so that the effectiveness of vitamin K supplementation for CVD prevention can be determined. The only trial identified for this review was judged to be at low risk of bias (so there was less chance of arriving at the wrong conclusions because of favouritism by the participants or researchers). However the evidence is limited to one small trial and no firm conclusions can be reached at this time.
We included adult patients aged 18 years and above undergoing elective surgery in the operating room setting. We found that the effects of drugs on the stress response was the subject of 72 studies. The investigators used 32 drugs. Promising results were seen in the reduction of arrhythmias with intravenous injections of beta blockers (drugs that decrease the heart rate), narcotics (drug used to treat pain), local anaesthetics, and calcium channel blockers (drugs that block movement of calcium). Serious side effects were only reported with high doses of narcotics and an increase in airway pressure was seen in some patients with beta blockers. Only local anaesthetic drugs clearly reduced the risk of myocardial ischaemia but this evidence came from only one trial. There was some difficulty in comparing and interpreting the results of these different trials. Patients at a high risk of complications were investigated in 17 trials. A reduction in arrhythmias with treatment was seen in this high risk group but the number of studies was too small to reach a conclusion. Doctors need to further research the effects of drugs used for blunting the haemodynamic response and their effect on outcomes in terms of morbidity, in a standardized manner.
It is used in pregnancy to study blood circulation in the baby, uterus and placenta. Using it in high-risk pregnancies, where there is concern about the baby's condition, shows benefits. However, its value as a screening tool in all pregnancies needs to be assessed as there is a possibility of unnecessary interventions and adverse effects. The review of trials of routine Doppler ultrasound of the baby’s vessels in pregnancy identified five studies involving more than 14,000 women and babies. The studies were not of high quality and were all undertaken in the 1990s. There were no improvements identified for either the baby or the mother, though more data would be needed to prove whether it is effective or not for improving outcomes.
This practice is based on studies which have shown the benefit of pancreatic enzymes on various outcomes such as abdominal pain, weight loss, analgesic use, fatty stools and quality of life. However, a collective conclusion about the role of pancreatic enzymes in chronic pancreatitis patients needs to be established from these studies. This systematic review aimed to collect all published and unpublished data on this subject in order to evaluate whether pancreatic enzymes have any benefit on various parameters in chronic pancreatitis, to compare different types of enzyme preparations and to evaluate whether different dosage schedules have any influence on the various outcomes. We included 10 studies in the review. These studies had enrolled small numbers of patients. Though individual studies showed benefit of varying degrees on the parameters mentioned above, we could not pool the results of these studies. With the evidence available so far, no definitive conclusion can be drawn for the benefit of pancreatic enzymes in patients with chronic pancreatitis.
The aim of this review is to find out which treatment, if any, is best. Only four of 32 reports identified met the inclusion criteria for this review; none showed a convincing benefit of any single drug over any others. Some treatments may be worth trying but staff should watch carefully for any side effects of the treatment (e.g. agitation or excessively dry mouth). Anxious relatives need explanation, reassurance and discussion about any fears and concerns associated with the terminal phase and 'death rattle'. Research in this difficult area is necessary to understand the cause of the noise, its effect on the patient and those around them and the best ways of managing this condition.
We searched medical databases up to December 2017 and included 14 studies involving 1469 participants with displaced or angulated middle third clavicle fractures. All participants were adults, ranging in age from 17 to 70 years, and there were more men than women. Ten studies compared plate fixation with conservative intervention (sling and/or figure-of-eight bandage), and four studies compared intramedullary fixation with wearing either a sling or a figure-of-eight bandage. Key results The review showed that surgery compared with conservative treatment may not improve upper arm function, pain and quality of life one year later. However, surgery may reduce the risk of treatment failure where secondary surgery is required for fractures that did not heal or that healed incorrectly. We are uncertain whether surgery provides a better cosmetic result overall. Although surgery reduces shoulder deformity, it can result in unsightly scars and prominent metalwork. We are also uncertain if there is a difference between surgery and conservative treatment in the risk of having a complication. However the nature of such complications often differs according to treatment. Complications of surgery, such as wound infection and opening, or hardware irritation requiring additional surgery, need to be balanced against complications more likely to occur with a sling, such as shoulder stiffness and failure of the fracture to heal properly. Quality of the evidence All 14 studies had weaknesses that could affect the reliability of their results. We considered that the evidence for all outcomes was either of low or very low quality. Conclusion Low-quality evidence indicates that surgery may not result in benefits over conservative treatment, or in more complications. However we are uncertain about these effects and further studies may change these conclusions.
This review assessed the effectiveness of increasing fruit and vegetable consumption as a single intervention without the influence of other dietary patterns or other lifestyle modifications in healthy adults and those at high risk of CVD for the prevention of CVD. We found 10 trials involving 1730 participants in which six examined the provision of fruit and vegetables to increase intake and four trials examined dietary advice to increase fruit and vegetable intake. There were variations in the type of fruit and vegetable provided but all interventions investigating provision involved only one fruit or vegetable component. There were also variations in the number of fruit and vegetables that participants were advised to eat. Some studies advised participants to eat at least five servings of fruit and vegetables a day while others advised at least eight or nine servings per day.The duration of the interventions ranged from three months to one year. Adverse effects were reported in three of the included trials and included increased bowel movements, bad breath and body odour. None of the included trials were long enough to examine the effect of increased fruit and vegetable consumption on cardiovascular disease events such as heart attacks. There was no strong evidence that provision of one type of fruit or vegetable had beneficial effects on blood pressure and lipid levels but most trials were short term. There was some evidence to suggest beneficial effects of dietary advice to increase fruit and vegetable consumption but this is based on findings from two trials. More trials are needed to confirm these findings.
In several clinical studies it was found that the respons of these tumours to radiotherapy was improved by adding hyperthermia. Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures (i.e. around 42 to 43 degrees Celcius during one hour) to damage and kill cancer cells.. This temperature is in itself able to kill tumour cells under certain conditions and also increases the lethal effect of radiation on tumour cells. can However, the results observed with this treatment were not consistent in subsequent clinical studies. Therefore we analysed the results of all clinical studies published so far comparing the treatment results of radiotherapy alone with the results of combined radiotherapy and hyperthermia in patients with locally advanced cervix carcinoma. The results do suggest a better outcome for patients treated with the combination of radiotherapy with hyperthermia. Thus following treatment a complete disappearance of the tumour was observed more regularly, regrowth of the tumour at the site of origin during follow up was observed less frequently and more patients were still alive at last follow-up. Treatment related side effects were not increased by the addition of hyperthermia to standard radiotherapy. However, the number of patients included in the clinical studies analysed is limited as the majority of patients had stage IIIB disease. The authors therefore conclude that hyperthermia may provide a clinically relevant improvement in treatment outcome for patients with locally advanced cervix carcinoma, in particular patients with stage IIIB disease. Additional clinical data are needed to warrant its use for all patients with locally advanced cervix carcinoma.
This review of four trials, which included 94 participants, found there is not enough evidence to decide if water-based exercises may reduce disability after stroke. There is a lack of hard evidence for water-based exercises after stroke. More research is therefore needed.
The trials reviewed compared duloxetine against dummy placebo tablets and also pelvic floor muscle training in women with predominantly stress urinary incontinence. Duloxetine reduced the frequency of episodes of incontinence and improved quality of life scores. However, it had little impact on the numbers cured and commonly had side effects, especially nausea. More studies comparing a serotonin and noradrenaline reuptake inhibitor with placebo and surgery are required, especially if conducted independently of pharmaceutical companies.
We reviewed the medical literature up to April 2015, and found 11 studies that included a total of 1817 people. Nine studies investigated the effects of medication (i.e. levodopa-carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on fatigue. Two studies investigated the effects of exercise on fatigue. We found no studies that investigated the effect of cognitive-behavioural therapy. We found that doxepin (one study, 12 people, low quality evidence), a drug to treat depression, may reduce fatigue. We found that rasagiline (one study, 1176 people, high quality evidence), an anti-Parkinson drug, reduced or slowed down the progression of physical fatigue. Most drugs were safe; however, levodopa-carbidopa (one study, 361 people, high quality evidence) may cause nausea. We found no evidence that exercise (two studies, 57 people, low quality evidence) reduces fatigue in Parkinson's disease. Based on the current evidence, it is not clear what treatment is most effective to treat fatigue in people with Parkinson's disease. Future studies should investigate the effect of cognitive-behavioural therapy on fatigue in people with Parkinson's disease.
In our review, regular intake of extra calcium tablets during pregnancy did not improve the number of preterm births or other infant outcomes, except for a slight increase in infant birthweight in the group of women who received calcium supplementation. Most studies included in this review were assessed as of low risk of bias, and evidence for specific outcomes was graded as of moderate quality, Taking calcium supplementation did not appear to have any obvious side effects. Our review included 25 randomised controlled studies, but only 23 studies involving 18,587 women contributed outcome data. The majority of the evidence was based on fewer numbers of studies.
The evidence is current to February 2015. We identified 25 trials, including 4121 participants with acute bacterial meningitis of which seven were performed in adults (over 16 years old), two included both children and adults and the other were performed in children. In 22 studies the corticosteroid used was dexamethasone, in three others hydrocortisone or prednisone were used. Nine studies were performed in low-income countries and 16 in high-income countries. This review found that the corticosteroid dexamethasone did not significantly reduce the death rate (17.8% versus 19.9%). Patients treated with corticosteroids had significantly lower rates of severe hearing loss (6.0% versus 9.3%), any hearing loss (13.8% versus 19.0%) and neurological sequelae (17.9% versus 21.6%). An analysis for different bacteria causing meningitis showed that patients with meningitis due to Streptococcus pneumoniae (S pneumoniae) treated with corticosteroids had a lower death rate (29.9% versus 36.0%), while no effect on mortality was seen in patients with Haemophilus influenzae (H influenzae) and Neisseria meningitidis (N meningitidis) meningitis. In high-income countries, corticosteroids reduced severe hearing loss, any hearing loss and short-term neurological sequelae. There was no beneficial effect of corticosteroid therapy in low-income countries. Corticosteroids decreased the rate of hearing loss in children with meningitis due to H influenzae (4% versus 12%), but not in children with meningitis due to other bacteria. Dexamethasone increased the rate of recurrent fever (28% versus 22%) but was not associated with other adverse events. Out of 25 studies, four were of high quality, 14 of medium quality and seven of low quality, leading to a moderate overall quality of evidence.
We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. We checked 1348 titles and abstracts of potentially relevant references, but we identified no randomised controlled trials (RCTs) that met our inclusion criteria. We identified trials of interest, but they were deemed not relevant because of their focus on diagnostic outcomes and examination of how sensitive tests are, rather than on the effects of different follow-up strategies on long-term outcomes. Currently no evidence indicates whether hrHPV post-treatment testing is better or worse in terms of important long-term clinical outcomes. This review highlights the need for good quality trials in this area that do not focus solely on the diagnostic accuracy of testing. We found no evidence from RCTs to inform decisions about the best surveillance strategy following treatment for CIN. A prognostic systematic review is needed to investigate the risks and benefits of different follow-up strategies for women after LLETZ treatment.
We have included ten randomised controlled trials with a total of 959 participants in this review. Eight of these trials compared azithromycin (a macrolide antibiotic) to placebo and two compared different doses of azithromycin. Four trials in children and adults (549 participants) showed significant improvements in lung function after treatment with azithromycin compared to placebo at six months; although data from later time points are not so clear. Patients treated with azithromycin were about twice as likely to be free of pulmonary exacerbation; needed fewer oral antibiotics and had fewer instances of Staphylococcus aureus in cultures from their lungs and airways. Adverse events were not common and not obviously associated with azithromycin, although there was an increase in resistance to macrolides. Most studies used a three times a week dosing schedule. Taking a high weekly dose was linked to an increase in mild gastrointestinal adverse events. Further multicentre studies are needed to look at the long-term effects of this antibiotic treatment, especially for infants diagnosed through newborn screening.
We found 12 studies that included a total of 2146 participants. Eleven studies including 2014 adult participants compared oral 5-ASA to a placebo (i.e. inactive pills or tablets). One study including 132 children compared oral 5-ASA to a placebo. Eleven studies were conducted for 12 months and one study was conducted for 24 months. Seven studies were judged to be of high quality and the other studies were judged to be of unclear quality because insufficient details were reported to allow for a judgement about quality. The studies with insufficient details were generally older studies that were published 20 or more years ago. A combined analysis of eleven studies including 2014 adult participants found no difference between oral 5-ASA (at daily doses between 1.6 g to 4 g) and placebo in the proportion of participants who remained in remission at 12 months. Similarly, a study including 161 adult participants found no difference between oral 5-ASA (at a dose of 2 g per day) and placebo in the proportion of participants who remained in remission at 24 months. The study involving children found no difference between oral 5-ASA (at a daily dose of 50 mg/kg) and placebo in the proportion of participants who remained in remission at 12 months. There does not appear to be an increased risk of side effects in people who take oral 5-ASA compared to placebo. Common adverse events reported in the studies included diarrhoea, nausea and vomiting, abdominal pain, headache and skin rash. In conclusion, there is no evidence that oral 5-ASA is superior to placebo for helping people with Crohn's disease remain in remission that was achieved by medical therapy.
We identified 33 randomised controlled trials involving 8244 patients from six countries, mainly the USA, in a range of clinical settings. Most interventions, which included written materials (for example, question prompt sheets) and coaching sessions, were delivered in the waiting room immediately before the consultation. They were compared to dummy interventions or usual care. Health issues included primary care and family medicine, cancer, diabetes, heart problems, women's issues, peptic ulcer and mental illness. We found small increases in question asking and patient satisfaction and a possible reduction in patient anxiety before and after consultations. We also found a possible reduction in patient knowledge and a possible small increase in consultation length. Both coaching and written materials produced similar effects on asking questions but coaching had a larger benefit in terms of patient satisfaction. Interventions immediately before the consultation led to a small increase in patient satisfaction whereas giving the intervention some time before did not. Interventions immediately before the consultation also resulted in small increases in consultation length, particularly when using written materials rather than coaching. Interventions some time before the consultation did not alter consultation time. The interventions seem to help patients ask more questions in consultations, but do not have other clear benefits. Doctors and nurses need to continue to try to help their patients ask questions in consultations and question prompt sheets or coaching may help in some circumstances.
Only one trial was identified. In this trial enrolling infants with gram-negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a three-fold increased risk for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics should be avoided. Further trials comparing these interventions are not justified in newborn infants.
Our synthesis included 11 studies, involving around 267 participants; five more studies are awaiting classification. We identified several potential barriers and facilitators to the use of protocols. First, doctors used protocols only in certain circumstances; otherwise they preferred to wean using their own knowledge and skills. Relatively inexperienced nurses often lacked confidence. A protocol could encourage their involvement in weaning because it set out clear instructions and also helped them to feel more secure. Although more experienced nurses also recognized these positive qualities, they criticized protocols as sometimes instructing them to wean contrary to their own clinical judgement. Second, the practical arrangements for care within an ICU could either help or hinder healthcare professionals to work together, and in this way influence how (well) a protocol was used. Third, the use of a protocol reflected how healthcare professionals interact with one another generally. For example, the degree of experience a nurse or doctor possessed could influence the confidence others had that they could wean safely. For this reason, doctors tended to be reluctant to involve nurses they considered to be relatively inexperienced in weaning, even when there was a protocol in place. Furthermore, the fact that doctors occupied a higher professional status or position meant that it was difficult for nurses to be involved in weaning, including by using a protocol, unless the doctors s/he worked with permitted this to happen. We developed 35 summary statements. Of these: we assessed 17 statements as ‘low’ confidence, largely because the evidence used to develop them came from only a small number of studies. We rated 13 statements as ‘moderate’ confidence, largely because the evidence used to develop them came from very well-conducted studies, and we rated five statements as ‘high’ confidence, largely because the evidence used to develop them came from a majority of the studies.
This review was undertaken to determine the best use of platelet transfusions for the prevention of bleeding in patients who have haematological disorders and are receiving intensive (myelosuppressive) chemotherapy or stem cell transplantation. The review aimed to look at three main topics. One, what is the evidence to indicate if platelet transfusions should be given to prevent bleeding as compared to a strategy aimed at transfusion when bleeding occurs? Second, if platelet transfusions are given to prevent bleeding, when should they be given, for example, at what level of platelet count when measured in a blood sample? Three, if platelet transfusions are given what platelet dose should be used? We are unable to answer the first question, however new data from two large studies should be available when this review is updated in approximately two years time. With regard to the second question, there is no evidence to suggest a change from the current practice of using a platelet count of 10 x 109/L to trigger the use of platelet transfusions to prevent bleeding. However, more research is required to clarify this issue. The final question can be answered. Using a lower platelet dose did not lead to an increased risk of bleeding and fewer platelets were required. The reduction in the number of platelets used should, theoretically, reduce the risk of adverse events although no true differences were seen in the studies. However, adverse events are uncommon and therefore a statistically significant difference may not be seen.
In March 2017 we searched for randomised controlled trials looking at the effects of systemic antibiotics on malignant wounds. We found only one trial, dating from 1984, which compared the effectiveness of the antibiotic metronidazole with a placebo (sugar pill) on six participants with malignant wounds resulting from breast cancer. The trial was a cross-over trial which means that participants receive both the treatment being tested and the comparison treatment, at different time-points, with a break between the treatments to ensure that the effects of the first treatment have worn off before the second treatment is taken. This is called the 'washout' period. In the one trial in this review, half the participants took the antibiotic first, for 14 days, and half took the placebo. Both groups then had 14 days with no medication before swapping over (cross-over) and trying the alternative treatment for 14 days. It is unclear if metronidazole reduces the smell of malignant wounds when taken orally (by mouth) in tablet form, without any side effects occurring. Its effectiveness in relation to other outcomes such as pain or quality of life was not measured in this trial. No change in the size or appearance of participants' tumours was reported. It is uncertain whether metronidazole reduces the smell of malignant wounds when taken orally in tablet form because the quality of the evidence is very low. This evidence came from a very small study with serious study design flaws, and more research is needed involving more people with different types of cancer. Trials looking at how antibiotics can affect other outcomes, such as quality of life, pain relief and reducing any bleeding or ooze from the wound are also needed. This plain language summary is up to date as of March 2017.
Thirty-five RCTs covering 2861 patients were included in this systematic review. There is insufficient evidence to make any recommendations about acupuncture or dry-needling for acute low-back pain. For chronic low-back pain, results show that acupuncture is more effective for pain relief than no treatment or sham treatment, in measurements taken up to three months. The results also show that for chronic low-back pain, acupuncture is more effective for improving function than no treatment, in the short-term. Acupuncture is not more effective than other conventional and "alternative" treatments. When acupuncture is added to other conventional therapies, it relieves pain and improves function better than the conventional therapies alone. However, effects are only small. Dry-needling appears to be a useful adjunct to other therapies for chronic low-back pain.
This review of existing studies was carried out by the Cochrane Oral Health Group, and the evidence is current as of December 2012. In this review there are 10 studies published between 2005 and 2011 in which a total of 354 children were randomised to receive treatment with a distalising orthodontic appliance and compared to either no treatment, headgear or another distalising appliance. The age range of children in nine of the studies was from 11 to 15 years, although the children recruited to one study were younger, from nine to 10 years old. Both girls and boys participated in the studies. Where it was mentioned, the funding was from a university or dental research foundation. The authors did not assess the impact of the funding sources. When intraoral appliances are compared to headgear they will probably move the upper molar teeth backwards more than headgear. However, the use of intraoral appliances was also associated with movement of the upper front teeth when compared to extraoral appliances in four studies. This is an unwanted effect that was not observed with the use of the headgear appliances. Harm, injury from the appliances and other characteristics of the appliances which may be important to patients were not reported in the studies. The evidence presented is generally of low quality. The main shortcomings were related to trial design.
We did a computer search for randomized controlled trials comparing four-phase birth control pills with one-phase birth control pills. We also wrote to researchers and makers of birth control pills to find other trials. Studies had to report on pregnancy, bleeding problems, side effects or stopping the use of pills. We did not include studies where the pills were used as a treatment for disorders like acne, hirsutism, polycystic ovary syndrome, bleeding problems or endometrioses, or where the pills were administered for less than three months. We assessed whether the studies were conducted properly. We included one study comparing a four-phase pill composed of the progestogen dienogest and the estrogen estradiol valerate with an one-phase pill composed of the progestogen levonorgestrel and the estrogen ethinylestradiol. Four-phase birth control pills and one-phase birth control pills had similar pregnancy rates. The number of women with blood loss in the period between two menstruations was similar for four-phase pills and one-phase pills. More women using one-phase birth control pills had a menstruation compared to women using four-phase birth control pills. The number of women who stopped using the pills because of side effects was similar for four-phase pills and one-phase pills. Breast pain was reported more frequently by women who used four-phase birth control pills than women who used one-phase birth control pills. The presence of only one study made it impossible to adequately compare four-phase birth control pills with one-phase birth control pills. More studies are needed to determine whether four-phase pills have advantages over one-phase pills. Until then, we recommend one-phase pills containing 30 μg estrogen for women starting to use birth control pills.
We identified 11 trials that enrolled 428 adult participants. These trials were conducted in various countries, including the Czech Republic, Brazil, Italy, Iran, China, Korea, Mexico, Turkey, USA, and UK. Ten out of 11 trials used a paired-eye design, in which one eye of each participant received LASEK and the other eye received PRK. The remaining trial included one eye of six participants and both eyes of 15 participants. Most participants included in the trials had low to moderate myopia. The evidence is current as of 15 December 2015. Because these trials reported different outcomes at different time points, it is difficult to compare the effectiveness of LASEK versus PRK across trials. We assessed our primary outcomes 12 months after the surgeries were performed. Available data were insufficient to clarify whether LASEK performed better than PRK with respect to correcting visual acuity to 20/20 or better, achieving within 0.50 diopters of target refraction, or preventing loss of corrected visual acuity. Data were insufficient for assessment of whether differences between procedures in adverse outcomes occurred at 12 months after the surgeries. At 24 months post treatment, one trial reported that eyes treated LASEK with may have better corneal haze scores than those treated with PRK, but that the difference may not be noticeable. Available data were insufficient for investigation of whether LASEK or PRK is better at correcting near-sightedness. We judged the evidence for most outcomes as very low to moderate quality because of variation in reporting and differences in effects among trials.
The studies in this review took place in nine countries in Africa, Asia and Latin America, in both rural and urban areas. Most of the studies looked at the supervision of health care professionals (including nurses, midwives, health officers and physicians), while two studies examined the effect of supervision on community or lay health workers. The number of supervisory visits generally varied from one to six over a period of up to nine months. What happens when health workers are supervised? The evidence was of low to very low quality and the studies showed mixed results. Compared to no supervision, some studies showed that supervision had a small benefit on health worker practices and knowledge, while other studies showed no benefit or were inconclusive. We are therefore uncertain about the effects of supervision on the quality of primary healthcare services. A summary of this review for policy-makers is availablehere
The researchers searched the medical literature up to March 2014, and identified 33 medical studies that investigated the use of tissue adhesives for closure of wounds. They compared tissue adhesive with another method of closure such as sutures, staples, tape, or another type of tissue adhesive. The main outcomes of interest were whether wounds stayed closed - and did not break down - and whether they became infected. The results of the review showed clearly that fewer wounds broke down when sutures were used. Studies also reported that some types of tissue adhesives might be slightly quicker to use than other types. There was no clear difference between tissue adhesives and the alternative closure methods for cosmetic results or costs. Results regarding surgeons' and patients' preferred skin closure method were mixed.
We searched the medical literature for clinical studies comparing the transport of adults who had major injuries by helicopter ambulance (HEMS) or ground ambulance (GEMS). The evidence is current to April 2015. We found 38 studies which included people from 12 countries around the world. Researchers wanted to find out if using a helicopter ambulance was any better than a ground ambulance for improving an injured person's chance of survival, or reducing the severity of long-term disability. Some of these studies indicated some benefit of HEMS for survival after major trauma, but other studies did not. The studies were of varying sizes and used different methods to determine if more people survived when transported by HEMS versus GEMS. Some studies included helicopter teams that had specialized physicians on board whereas other helicopter crews were staffed by paramedics and nurses. Furthermore, people transported by HEMS or GEMS had varying numbers and types of procedures during travel to the trauma center. The use of some of these procedures, such as the placement of a breathing tube, may have helped improve survival in some of the studies. However, these medical procedures can also be provided during ground ambulance transport. Data regarding safety were not available in any of the included studies. Road traffic and helicopter crashes are adverse effects which can occur with either method of transport. Overall, the quality of the included studies was low. It is possible that HEMS may be better than GEMS for people with certain characteristics. There are various reasons why HEMS may be better, such as staff having more specialty training in managing major injuries. But more research is required to determine what elements of helicopter transport improve survival. Some studies did not describe the care available to people in the GEMS group. Due to this poor reporting it is impossible to compare the treatments people received. Based on the current evidence, the added benefits of HEMS compared with GEMS are unclear. The results from future research might help in better allocation of HEMS within a healthcare system, with increased safety and decreased costs.
Study characteristics: We included sixteen randomised controlled trials (1063 participants) comparing Tong-xin-luo capsules plus conventional treatment with placebo plus/or conventional treatment (literature search date: though June 2014). All studies were undertaken in China. The sample size was from 50 to 178 and the duration of follow-up ranged from three months to two years. Key results: We found that Tong-xin-luo may possibly reduce the risk of narrowing of a blood vessel detected by angiography, cardiovascular events (including myocardial infarction, angina and heart failure) and use of repeat procedure. Adverse events were seldom reported. Quality of evidence: Because of high risk of bias for fifteen studies, imprecision and possible publication bias, the quality of evidence was low or very low for all study outcomes.
This review of randomized controlled studies looked at the different timing options for administration of prophylactic antibiotics to prevent infectious complications in women undergoing cesarean delivery. We compared preoperative administration to administration after the cord had been clamped. The review includes 10 studies (with data from 5041 women). The studies were at a low risk of bias. Antibiotics given to women before cesarean delivery nearly halved the risks of combined infections (43%), endometritis (46%), and wound infection (41%) compared to giving the antibiotics after clamping of the baby’s umbilical. Other maternal infections such as urinary or lung infections were no different between the two groups of women, nor were adverse effects in newborns. High quality evidence shows that preoperative intravenous antibiotic administration decreases postpartum infections and is, therefore, beneficial for the mother. Maternal side effects were not consistently reported. Numbers were limited with respect to information on newborns and any adverse outcomes. Further research may be needed to determine adverse effects on the babies.
This review did not find any high quality randomised controlled trials that examined the effectiveness of such multidisciplinary care, either when originally published in 2009 or for the update in 2011. The evidence from low quality studies suggests that such care may improve some aspects of quality of life, reduce the frequency of hospitalisation and hospital length of stay and improve disability in persons with ALS or MND. The evidence for multidisciplinary care on survival is conflicting. The gap in current research should not be interpreted as proof that multidisciplinary care is ineffective. Further research into types of appropriate studies, caregiver needs and various aspects of multidisciplinary care in the MND population is needed.
These days the drugs of the latter type that are used for acute COPD are salbutamol and terbutaline, but neither of these drugs have been used in the only studies that we could find. We found only three small studies. Overall, both types of drug showed a small but worthwhile effect. There was no difference between them. Our review was not designed to test whether they would have had a greater effect if both were given at the same time.
This review included 17 randomized controlled trials (RCTs) including a total of 1806 participants. Five RCTs (411 participants) compared acupuncture to sham acupuncture for the treatment of IBS. Sham acupuncture is a procedure in which the patient believes he or she is receiving true acupuncture. However, in sham acupuncture the needles either do not penetrate the skin or are not placed at the correct places on the body, or both. Sham acupuncture is intended to be a placebo for true acupuncture. The sham-controlled studies were well designed and of high methodological quality. These studies tested the effects of acupuncture on IBS symptom severity or health-related quality of life. None of these RCTs found acupuncture to be better than sham acupuncture for either of these two outcomes, and pooling the results of these RCTs also did not show acupuncture to be better than sham acupuncture. Evidence from four Chinese language comparative effectiveness trials showed acupuncture to be superior to two antispasmodic drugs (pinaverium bromide and trimebutine maleate), both of which provide a modest benefit for the treatment of IBS, although neither is approved for treatment of IBS in the United States. It is unclear whether or not the greater benefits of acupuncture reported by patients in these unblinded studies are due entirely to patients’ greater expectations of improvement from acupuncture than drugs or preference for acupuncture over drug therapy. There was one side effect (i.e. fainting in one patient) associated with acupuncture in the nine trials that reported side effects, although relatively small sample sizes limit the usefulness of this safety data.
Using a systematic approach, the medical literature was searched thoroughly to find reliable studies that looked at the effects of improving patients' knowledge about asthma, but which did not attempt to improve practical self-management skills. The results of the studies were combined to see if patient education designed to improve patient knowledge about their condition made a difference to their asthma. Improving patient knowledge alone does not seem to reduce hospitalisations, doctor visits or medication use for asthma, but may play a role in improving patients perceptions of their symptoms. However, education programmes designed to improve knowledge alone may reduce Emergency Room visits in high-risk adults.
This review evaluated the effects of giving people at high risk for HIV infection drugs to prevent infection (called antiretroviral pre-exposure prophylaxis, or PrEP). We found six randomised controlled trials that assessed the effects of oral tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) versus placebo; TDF versus placebo, and daily TDF-FTC versus intermittent TDF-FTC. One of the trials had three study arms (TDF, TDF-FTC and placebo arm). The trials were carried out amongst different risk groups, including HIV-uninfected men who have sex with men, people in serodiscordant sexual relationships where one partner is infected and the other is not, and other high risk men and women. The findings suggests that the use of TDF alone or TDF+FTC reduces the risk of becoming infected with HIV. However, further studies are need to evaluate the method of administration (daily versus intermittent dosing), long-term safety and cost effectiveness of PrEP in different risk groups and settings.
The review covered 10 trials, involving 6533 women, and looked at several antioxidants. Overall the review found no reduction in pre-eclampsia, high blood pressure or preterm birth with the use of antioxidant supplements. When antioxidants were assessed separately, there were insufficient data to be clear about whether there was any benefit or not, except for vitamin C and E. The current evidence does not support the use of antioxidants to reduce the risk of pre-eclampsia or other complications in pregnancy, but there are trials still in progress.
We identified five Cochrane Reviews and three non-Cochrane reviews. The reviews varied in how many trials they included and the number of participants within trials. The quality of both the reviews and trials varied. We found moderate-quality evidence that three types of strategies probably help to reduce antibiotic prescribing in primary care. Strategies that encourage the use of shared decision making between doctors and their patients, C-reactive protein tests, and procalcitonin-guided management (both tests that measure the amount of proteins in the blood, which may be raised in the case of infection) all probably reduce antibiotic prescribing in general practice. Procalcitonin-guided management also probably reduces antibiotic prescribing in emergency departments. These strategies seem to change antibiotic prescribing whilst keeping patients happy with their consultation and ensuring that they did not need to return to their doctor for the same illness. There was no information about the cost of these strategies, so it was difficult to weigh up the benefits and costs. The quality of the evidence for strategies that aim to educate doctors about antibiotic prescribing, that provide decision aids for doctors to help them change their prescribing, and for the use of rapid viral diagnostics in emergency departments was either low or very low, meaning that we were unable to draw firm conclusions about the effects of these strategies. In conclusion, we determined that some strategies aimed at doctors can probably help to reduce antibiotic prescribing in primary care. Further studies are needed for other types of strategies where there is less information about whether they can change prescribing.
We found 20 studies that assessed the accuracy of measuring the blood level of CRP to diagnose infections in newborn infants. These studies were similar enough to justify a combined analysis of their findings. The combined analysis indicated that a positive CRP test correctly identified infants with infection about six times out of 10. Measuring the blood level of CRP is not sufficiently accurate to help early diagnosis of infection in newborn infants.
We found one randomised controlled trial with a total of 50 participants (25 in both the intervention and comparator group) and a follow-up of two years. The surgery used was 'laparoscopic adjustable gastric banding' (gastric band placed around the entrance of the stomach by means of keyhole surgery). The control group received a program consisting of reduced energy intake (individualised diet plans ranging between 800 and 2000 kcal per day, depending on age and weight), increased activity (target of 10,000 steps per day) with a structured exercise schedule of at least 30 minutes a day and behavioural modification. Australian adolescents (higher proportion of girls than boys) with an average age of 16.5 and 16.6 years in the gastric banding and 'lifestyle' group participated. The study authors reported an average reduction in weight of 34.6 kg at two years, representing a change in body mass index units (kg/m²) of 12.7 for the gastric banding group; and an average reduction in weight of 3.0 kg representing a change in body mass index units of 1.3 for the lifestyle intervention. Side effects were reported in 12 of 25 (48%) participants in the intervention group and in 11 of 25 (44%) in the control group. A total of 28% of the adolescents undergoing gastric banding required a 'revisional procedure' (surgery because of complications from the gastric banding surgery). No data were reported for all-cause mortality, behaviour change, participants views of the intervention and socioeconomic effects. At two years, the gastric banding participants performed better than the lifestyle participants in two of eight health-related quality of life concepts as measured by the Child Health Questionnaire (physical functioning score (94 versus 78, community norm 95) and change in health score (4.4 versus 3.6, community norm 3.5). Our results are limited to two years of follow-up and are based on just one small Australian study with some risk of bias which was conducted in a private hospital, receiving funding from the gastric banding manufacturer. There is currently insufficient evidence to make an informed judgement about surgery for the treatment of obesity in children and adolescents. This evidence is up to date as of March 2015.
We examined the results of RCTs that randomly allocated participants to one of two groups. In one group, trial participants received blood at lower blood counts. In the other group, trial participants received blood at higher blood counts. The data are current up to May 2016. We identified a total of 31 relevant trials, which involved 12,587 participants. All of the studies compared different policies for blood transfusions. We found that participants who were assigned to receive blood at lower blood counts were 43% less likely to receive a blood transfusion than those who were given blood at higher blood counts. The risk of dying within 30 days of the transfusion was the same whether the participants received transfusion at lower or higher blood counts. We also evaluated harmful events that occurred after participants received, or did not receive, blood transfusions, including infection (pneumonia, wound infection, and blood poisoning), heart attacks, strokes, and problems with blood clots, and found that there was no clear difference in the instance of these events between the group that received transfusions at lower blood counts and the group that received transfusions at higher blood counts. We found that most of the RCTs provided a high quality of evidence, in that they were adequately conducted and used appropriate methods that minimised any possible biases that could make the validity of the results uncertain. We concluded that it was not harmful to the participants' health status to give blood at lower or higher blood counts. If a policy of giving blood only at lower blood counts were followed routinely in clinical practice, it would reduce the amount of blood patients receive substantially and reduce the risk of patients receiving blood transfusions unnecessarily, as transfusions can have harmful effects. Additional studies are needed to establish the blood count at which a blood transfusion is needed in patients who have suffered a heart attack, brain injury, or have cancer.
The review included three studies with 263 people with tuberous sclerosis complex aged between 0.8 and 61 years of age. However, one study involved five people with sporadic lymphangioleiomyomatosis (without tuberous sclerosis complex) which we could not remove from the analysis. Studies compared rapamycin or rapalogs with placebo and people were selected for one treatment or the other randomly. The duration of the studies was variable. Two of the included studies were funded by Novartis Pharmaceuticals. There is evidence that oral everolimus (rapalog) increased the number of people who achieved a 50% reduction in the size of subependymal giant cell astrocytoma and renal angiomyolipoma. Oral everolimus also showed benefit in terms of response to skin lesions, although applying rapamycin to the skin only showed a tendency for improvement. Those who received treatment had a similar risk of experiencing adverse events as compared to those who did not receive treatment. However, more people receiving the active treatment had severe adverse events causing them to withdraw from the trial, temporarily stop treatment or reduce their dose compared to the control group. Two of the included studies generally showed a low risk of bias in study design, except for one study where it was unclear whether people knew which group they would be put into. Another included study showed different degrees of risk of bias with regards to study design, for example, due to missing data and lack of clarity about how people where put into the different groups. The results from the studies were generally of high quality, except for response to skin lesions from topical rapamycin due to missing outcome data and seizure frequency due to the way participants were selected.
This review evaluated the effectiveness and adverse effects of antimicrobial agents used to treat BV in non-pregnant women. Twenty-four trials involving 4422 women were reviewed. With regard to less treatment failure, clindamycin was superior to placebo but comparable to metronidazole, irrespective of the dose regimen. Metronidazole tended to cause a higher rate of adverse events, such as metallic taste and nausea and vomiting, than did clindamycin. Oral lactobacillus combined with metronidazole was more effective than metronidazole alone. Administered in an intravaginal gelatin tablet, lactobacillus was also more effective than oral metronidazole. Triple sulfonamide cream was less effective compared with clindamycin. Hydrogen peroxide douche was not as effective as a single 2 g dose of metronidazole yet caused more harms. Only one trial involved asymptomatic women and the result was not conclusive. There was insufficient evidence to reach a conclusion on the effectiveness of other promising drugs. Drugs effective for bacterial vaginosis include clindamycin preparations, oral metronidazole, and oral and intravaginal tablets of lactobacillus. Adverse effects of metronidazole include metallic taste, and nausea and vomiting. Information on possible side effects of lactobacillus preparations is required.
The historical use of amniotic membrane transplantation (AMT) to treat eye burns during the acute phase has re-emerged in recent years, although its precise effects on the healing process have not been proven by randomised controlled trials (RCTs). One RCT conducted in India included a subset of patients who fulfilled the criteria for analysis in this review. The participants included 68 men and women of all ages with chemical or thermal burns to the ocular surface, who were randomised to treatment with conventional medical therapy alone or to medical therapy and AMT in the first seven days after injury. Conventional medical therapy included topical steroids, antibiotics, sodium ascorbate, sodium citrate, tear substitutes and cycloplegic drops, and oral vitamin C. Pressure-lowering drops and/or oral acetazolamide were prescribed if required. Data from the RCT were analysed to compare corneal wound closure rates by the 21st day after the injury and visual outcomes at final follow-up. The burns were classified as moderate or severe. In the moderate category, the AMT group had a higher proportion of eyes with complete epithelial closure by day 21 (not statistically significant) and significantly better visual acuity at final follow-up. There was a high risk of bias resulting from the uneven characteristics of the control and treatment eyes at presentation and from the failure to mask personnel and outcome assessors involved in the study. This reduced confidence in the study findings.
In this review we found nine studies involving counselling in primary care for 1384 participants. There were some problems with the methods in some studies. The evidence suggested that counselling is better than usual general practitioner care in improving mental health outcomes in the short term, although the advantages are modest. People who receive counselling in primary care from a trained counsellor are more likely to feel better immediately after treatment and be more satisfied than those who receive care from their general practitioner. However, in the long term, counselling does not seem to be any better than GP care. Although some types of healthcare utilisation may be reduced, counselling does not seem to reduce overall healthcare costs. There is very limited evidence comparing counselling with other psychological therapies (2 studies with 272 participants) or with antidepressant medication (1 study with 83 participants).
This review assesses different intermittent drug techniques compared with maintenance treatment in people with schizophrenia or related disorders. Seventeen studies with 2252 participants compared intermittent drug techniques with standard maintenance on medication. Relapse was significantly higher in people receiving intermittent drug treatment. Hospitalisation was higher for people receiving intermittent drug treatment. Results suggest that intermittent treatment is not as effective as continuous or maintained treatment in preventing relapse. Although information favours maintenance and continuous treatment, this is not always the case in real settings, where people may stop their medication due to debilitating side effects that affect their quality of life. More research is needed to assess any potential benefits or harm of intermittent treatment, particularly regarding the side effects commonly associated with maintained antipsychotic treatment. There was no exploration of economic/money savings, specifically relating to the potential cost-effectiveness of intermittent techniques. Until further evidence is available concerning the potential benefits or harms of intermittent treatment, managers, psychiatrists and policy makers should consider it an experimental therapy. This plain language summary has been written by a consumer Ben Gray, Service User and Service User Expert, Rethink Mental Illness.
We reviewed the medical literature to find randomised controlled trials on care delivered by specialised nurse compared to care by a doctor in the management of asthma. We found five studies on 588 adults and children. The studies were of good methodological quality. The number of asthma exacerbations (flare-ups) and the level of asthma severity did not differ at the end of the study period between the intervention and the control group. Only one study reported information about the costs associated with both kinds of care and there was no significant difference between them. There was also no difference in quality of life. We found no difference between nurse-led care and physician-led care. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and healthcare costs.
We looked for all research studies (randomised controlled trials) published up to July 2018. We found six studies which included 221 participants, with an average age ranging from 59 to 70 years. These studies included different numbers of people, ranging from 20 to 111. Our results showed that, compared to those who did not exercise, people with lung cancer who did exercise were fitter and had a better quality of life. We did not find any difference in muscle strength, shortness of breath, tiredness, feelings of anxiety and depression, or lung function. No serious harms were reported in people with lung cancer who exercised, but only three studies talked about harms. The results of this review are not clear, mainly because of the small number of studies found, the small numbers of people in those studies, and because the studies did not seem to have been carried out to a high standard.
We found 19 studies, including 13,216 participants. Our results are presented along with a judgement of quality which reflects how certain we are about the results. We found that follow-up did not improve overall survival (high-quality evidence), colorectal cancer-specific survival (moderate-quality evidence), or relapse-free survival (high-quality evidence). If patients have follow-up, they are much more likely to have surgery if the cancer is detected again (high-quality evidence). With follow-up, more asymptomatic 'silent' cancer relapses are likely to be found at planned visits (moderate-quality evidence). Harmful side effects (harms) from tests were not common, but more intensive follow-up may increase harms (reported in two studies; very low-quality evidence). Costs may be increased with more intensive follow-up (low-quality evidence). More intensive follow-up probably makes little or no difference for quality of life (moderate-quality evidence). The information we have now suggests that there is little benefit from intensifying follow-up, but there is also little evidence about quality of life, harms, and costs. We do not know what is the best way to follow patients treated for non-metastatic (no secondaries) colorectal cancer, or if we should at all. We know little about the costs of follow-up in this setting. Consumer needs and concerns with respect to the value of follow-up require further research.
In patients with an irregular heart rhythm (atrial fibrillation), anticoagulant drugs, such as warfarin, prevent such clots forming and prevent stroke. However, anticoagulant drugs may also cause bleeding in the brain and this harmful effect could outweigh any benefits in patients with a normal heart rhythm. This review identified 11 trials, involving 2487 participants who had had a stroke (and also had a normal heart rhythm), of anticoagulants to prevent further strokes. There was good evidence that anticoagulants could cause serious bleeding, and there was no evidence that, in such patients, anticoagulants were of benefit in the prevention of further strokes. Other trials have shown that, in a person with a normal heart rhythm who has had an ischaemic stroke, antiplatelet drugs such as aspirin are a safe and effective way to reduce the risk of further strokes and heart attacks.
We searched the literature up to 24th March 2015 and included five trials involving 1277 women with early-stage OC in the review, and four good quality trials contributed data. Most women (more than 95%) had stage I OC. For this update, we identified one additional publication of 10-year follow-up results from a trial already included in the review, but found no new trials. We found high quality evidence that women diagnosed with early-stage OC who received AC after surgery to remove and stage the disease had a lower risk of dying within 10 years than women who did not receive AC (observation group), and a lower risk of the cancer returning in the 10 years after treatment (see Cates plot, Figures 4 to 7). Low quality evidence suggested that women with higher risk disease may have more to gain from AC, but we could not exclude a survival benefit for other early stage disease. Chemotherapy can have side effects but we found insufficient data to compare adverse events and long term risks between chemotherapy and observation groups. In early stage ovarian cancer, AC improves survival and reduces the risk of ovarian cancer recurring compared with no AC. Therefore AC in early stage disease should be considered in all women. However, it remains uncertain whether women with lower risk early stage disease will benefit much from AC and decisions to use AC should be mindful of this uncertainty, and the uncertainty regarding adverse events.
This blended, updated review included 10 randomised trials (N = 1923). It evaluated the effects of advice to rest in bed or stay active on individuals with acute low-back pain (pain lasting for less than 6 weeks) with or without sciatica. Moderate quality evidence shows that patients with acute LBP may experience small improvements in pain relief and ability to perform everyday activities if they receive advice to stay active compared to advice to rest in bed.  However, patients with sciatica experience little or no difference between the two approaches.  Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality evidence suggests those patients with or without sciatica experienced little or no difference in pain relief or function, regardless of whether they received advice to stay active, exercises or physiotherapy. Further research is very likely to have an important impact on the estimate of effect and is likely to change our confidence in it.
We searched the scientific databases for clinical studies evaluating the effects of bypassing agents in men with hemophilia A or B with inhibitors. We included four studies (duration 7 to 15 months), involving 116 individuals. Two studies compared the prophylactic infusion with bypassing agent to on-demand treatment (treatment given only after the bleeding occurred) and two studies compared high-dose to low-dose preventative therapies. Limited evidence showed that prophylactic use of bypassing agents reduced bleeding events, joint bleeding events and number of affected joints. There was no evidence for improved quality of life amongst those who received prophylaxis as compared to those who received on-demand therapy. There was no evidence for a difference in benefits or harms between high- and low-dose rFVIIa for prophylaxis. The overall quality of evidence of these studies was moderate to low as the included studies were small and provided limited information. Also, in one of the studies, up to 24% of the men recruited were not included in the analysis of the results, which further increases imprecision of results.
The aim of this review was to evaluate whether the use of fluoride toothpaste by children is associated with an increased risk of developing dental fluorosis in children. The review included 25 studies of different designs; some providing stronger evidence than others. There is some evidence that brushing a child's teeth with a toothpaste containing fluoride, before the age of 12 months, may be associated with an increased risk of developing fluorosis. There is stronger evidence that higher levels of fluoride (1000 parts per million (ppm) or more) in toothpaste are associated with an increased risk of fluorosis when given to children under 5 to 6 years of age. However, for some children (those considered to be at high risk of tooth decay by their dentist), the benefit to health of preventing decay may outweigh the risk of fluorosis. In such circumstances, careful brushing by parents/adults with toothpastes containing higher levels of fluoride would be beneficial.
This review concludes that single layer anastomosis is comparable to double layer anastomosis in terms of anastomotic leak, peri-operative complications, death rate and hospital stay. Single layer anastomosis consumes shorter operative time as compared to double layer. Therefore, single layer anastomosis may routinely be used for the anastomosis of gastrointestinal tract following bowel resection. However, since this conclusion is derived from smaller number of patients recruited in relatively moderate quality trials, further trials should be aimed to reduce the limitations of this review.
The review authors looked for studies in which such chemicals were given to OP poisoned patients, to see how effective the treatment is. They sought randomised controlled trials, a type of research study in which one group of patients is given one treatment, while a similar group (the control group) is given a different treatment. The authors found eight studies but only two small randomised controlled trials, one using higher dose sodium bicarbonate and the other a lower dose. Only the trial using higher dose sodium bicarbonate, which included 53 participants, showed a slight benefit from using sodium bicarbonate in conjunction with standard treatment for OP poisoning. This study does not provide enough evidence to recommend routine clinical use of sodium bicarbonate. There are hundreds of different kinds of OPs so treatment may vary based on the type of poisoning as well as the severity of the poisoning. More research needs to be done to determine the best treatment for poisoning with OPs in various situations.
This systematic review and meta-analysis, which is the first in this field, shows a significant beneficial effect on both overall (OS) and disease-free survival (DFS) for patients undergoing postoperative chemotherapy after removal of their primary rectal tumour. Further investigation is needed to define the role of postoperative chemotherapy in the multimodal treatment of patients with rectal carcinoma: for instance, modern anti-cancer agents (including so called "smart drugs") and integration with neoadjuvant therapy (such as preoperative chemoradiation) should be taken into consideration in order to improve the encouraging findings of this meta-analysis.
This systematic review is important because review authors assessed the risk of important outcomes after lower-limb revascularization with the participant under neuraxial or general anaesthesia. They performed this systematic review to answer a single research question: What are the rates of death and major complications with spinal and epidural anaesthesia as compared with other types of anaesthesia for lower-limb revascularization? In this second update of the Cochrane review, we searched the databases until April 2013 but found no new studies. The total number of participants in the four included studies was 696, of whom 417 received neuraxial anaesthesia and 279 received general anaesthesia. No evidence revealed differences in postoperative risk of death, myocardial infarction or leg amputation between the two types of anaesthetic. The risk of pneumonia was 9% after neuraxial anaesthesia and 20% after general anaesthesia. Evidence was insufficient to show the effects of neuraxial anaesthesia compared with other types of anaesthesia on cerebral stroke, duration of hospital stay, postoperative cognitive dysfunction, complications in the anaesthetic recovery room and transfusion requirements. No data described nerve dysfunction, postoperative wound infection, patient satisfaction, postoperative pain score, claudication distance and pain at rest. One study recruited more than 50% of all reported cases.This systematic review shows that neuraxial anaesthesia may reduce the risk of pneumonia after lower-limb revascularization, but evidence is insufficient to support other benefits or harms.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and other databases for clinical trials comparing manual rotation with expectant management (waiting), speeding up of labour or operation. The women were at term (at least 37 weeks of pregnancy). The results are current to October 2014. We found only one small pilot trial involving 30 women that assessed the feasibility of manual rotation versus routine care (no manual rotation). The study reported no clear difference for the review's primary outcomes of operative delivery (vacuum-assisted delivery or forceps delivery (or both), or caesarean section) and no mother or baby deaths. In terms of adverse events, there were no reported cases of umbilical cord prolapse or cervical laceration and a single case of a non-reassuring or pathological cardiotocograph during the procedure. Further research is needed to assess the effect of manual rotation in second stage of labour to reduce operative delivery rates. We considered the study at low risk of bias but it did not have sufficient participants to detect important clinical benefits or harms of manual rotation to correct the baby's position in second stage of labour.
We found 11 trials involving a total of 776 men across eight countries for this review. A combination of results from six trials involving a total of 404 participants indicated that men with urethral stricture who perform intermittent self-dilatation may have less chance of their urethral stricture coming back than men with a urethral stricture who do not perform intermittent self-dilatation. We can not be confident about this finding, however, because the quality of the evidence was very low. There were no trials that looked at whether intermittent self-dilatation is a cost-effective health care intervention and there were no trials that used reliable health questionnaires to find out whether intermittent self-dilatation reduces men's urinary symptoms or improves their overall well being. On the whole the trials did not report side effects in a way that was useful for estimating the risks of performing intermittent self-dilatation. We do not know yet whether certain types of catheter are better than others for performing intermittent self-dilatation. It is also unclear how often or for how long men should perform intermittent self-dilatation to give themselves the best chance of staying free from urethral strictures. The trials in this review were generally small and poorly designed or poorly explained. All of the trials were conducted in a way which meant they had a high chance of generating an answer that does not represent the truth.
The evidence was current to August 2017. We found 38 studies that were conducted between 1993 and 2016 with 3187 participants that made 23 comparisons between different treatments in men with CP/CPPS. The evaluated interventions usually implied the use of devices, medical advice or some form of physical therapy. In many cases, these therapies were given to men in an outpatient setting. Most studies did not specify their funding sources; three studies reported funding from device makers. Acupuncture: we found that acupuncture (an alternative medicine where thin needles are inserted into the skin at specific points) probably causes a significant decrease in symptoms of prostatitis and may not associated with side effects when compared with pretend acupuncture, however, it may not reduce sexual problems. It probably decreases symptoms when compared with standard medical therapy. We found no information on its effect on quality of life, depression or anxiety. Lifestyle modifications: we are uncertain whether the recommendation of lifestyle modifications reduces symptoms when compared to the continuation of the same lifestyle. We had no information regarding side effects, sexual problems, quality of life, depression or anxiety. Physical activity: we found that a physical activity programme may reduce symptoms (small effect) when compared with a non-specific activity used as a control, however it may not reduce anxiety or depression. We have no information regarding side effects, sexual problems or quality of life. Prostatic massage: we are uncertain whether the prostatic massage reduces or increases symptoms when compared with no massage. We found no information regarding side effects, sexual problems, quality of life, depression or anxiety. Extracorporeal shockwave therapy: we found that extracorporeal shockwave therapy (where shock waves are passed through the skin to the prostate) causes a significant decrease in symptoms compared to a simulated procedure. These results may not be lasting after more continued treatment. This treatment may not be associated with side effects. We have no information regarding quality of life, depression or anxiety. Transrectal thermotherapy compared to medical therapy: we found that transrectal thermotherapy (which applies heat to the prostate and pelvic muscle area) alone or in combination with medical therapy may cause a small decrease in symptoms compared to medical therapy alone. One of the included studies reported that participants may experience transient side effects. We have no information regarding sexual problems, quality of life, depression or anxiety. There is uncertainty about the effects of other interventions. The quality of the evidence was low in most cases, meaning that there is much uncertainty surrounding the results. The included studies were not well designed, had a small sample size and had a short follow-up time (usually 12 weeks).
Searches of all relevant sources of medical information identified 7558 articles, and, after initial screening of all these articles, we selected 45 as being suitable for this review. On reading the summaries of these 45 trials, 10 were suitable to be included in this review. We included trials that looked at the effects of a nutritional intervention in adults aged 18 years or over having radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic cancer. We excluded patients with stomas and a previous history of inflammatory bowel disease. Results showed that studies evaluating dietary changes, including changes in dietary fat, fibre and lactose, during radiotherapy reduced diarrhoea at the end of treatment. However, these dietary changes did not seem to improve patients' weights. While some changes to diet during radiotherapy may benefit patients by reducing diarrhoea, it is important to recognise that some of the studies reviewed were dated and there have been changes in radiotherapy technique since then that may give patients less diarrhoea anyway. In addition, many studies were of poor quality and, therefore, only a small number were able to be included in this review. Some interventions described, for example, having to take a liquid diet, were not acceptable as many patients found them difficult to tolerate and were unable to take them completely.
In one study that had 21 participants, radioactive beads (injected into the blood vessels of the liver) given with chemotherapy (into the veins of the arm) was more effective at controlling the cancer and improving how long people lived than chemotherapy given on it's own. However, in this study more people who received the radioactive beads suffered from side effects and this study used an older type of chemotherapy that is less effective than the newer treatments that are now available. In a second study with 63 participants, radioactive beads were given with chemotherapy that was injected directly into the blood vessels of the liver. In this study there was no extra benefit in the control of cancer growth or survival for those participants who received radioactive beads in addition to the chemotherapy. More studies are needed with a particular focus on whether radioactive beads provides extra benefit when given with newer chemotherapy treatments, and if radioactive beads provide benefit when given on their own.
Two of the studies had serious design weaknesses with regard to their methods for selecting participants, three with regard to the application of the test (MMSE), and nine with regard to the presentation of flow and timing. We were able to do a combined statistical analysis (meta-analysis) on 28 studies in the community setting (44 articles) and 6 studies in primary care (8 articles), but we could not extract usable data for the remaining 14 community studies. Two of the six studies in primary care were conducted in people who had symptoms of possible dementia. We were able to calculate the summary diagnostic accuracy of the MMSE at three cut points in community-based studies, but we didn't have enough data to do this in the primary care studies. A perfect test would have sensitivity (ability to identify anyone with dementia) of 1.0 (100%) and specificity (ability to identify people without dementia) of 1.0 (100%). For the MMSE, the summary accuracy at a cut point of 25 (10 studies) was sensitivity 0.87 and specificity 0.82. In seven studies that adjusted accuracy estimates for level of education, we found that the test had a sensitivity of 0.97 and specificity of 0.70. The summary accuracy at a cut point of 24 (15 studies) was sensitivity 0.85 and specificity 0.90. Based on these results, we would expect 85% of people with dementia to be correctly identified with the MMSE, while 15% would be wrongly classified as not having dementia; 90% of those tested would be correctly identified as not having dementia whilst 10% would be false positives and might be referred for further testing. Our results support the use of the MMSE as part of the process for deciding whether or not someone has dementia, but the results of the test should be interpreted in broader context of the individual patient, such as their personality, behaviour and how they are managing at home and in daily life.
We identified 13 randomised controlled trials. They were all conducted in trachoma-endemic countries (mostly in sub-Saharan Africa) with surgical interventions carried out by non-physician surgeons. Five studies compared different surgical treatments. Three studies investigated whether azithromycin antibiotic treatment after surgery improves the results. One study compared different types of sutures. One study compared surgery to the pulling out of eyelashes (epilation). One study compared the outcomes of treatments provided in the community with hospital care. One study compared the results of surgery performed by eye doctors with those of non-specialist technicians. The evidence is current to May 2015. Most studies were funded by government research councils or charitable foundations. These trials suggested that the most effective surgery requires full-thickness incision of the tarsal plate and rotation of the edge of the eyelid. The use of a surgical lid clamp improves eyelid contour outcomes and reduces granuloma formation. Silk and absorbable sutures give comparable results. The addition of azithromycin treatment at the time of surgery may reduce post-operative trichiasis under certain conditions. Epilation is less effective than surgery at treating trichiasis, but has comparable results for vision and corneal change two years after intervention. Community-based surgery was more convenient for patients by reducing the time and expense of travelling to a conventional hospital, and it did not increase the risk of complications or recurrence. Surgery performed by ophthalmologists and by integrated eye care workers were both similarly effective. Destroying the lash roots by freezing or electrical ablation appeared to have low success rates and the equipment required is costly and can be difficult to maintain. The quality of the evidence from these randomised controlled trials was variable. Most were of a high quality. However, several were relatively small in size and several had potential bias problems due to the method of randomisation and masking.
This review synthesized the results of five randomized controlled trials of social skills groups including 196 individuals with autism spectrum disorders (aged 6 to 21 years). We found individuals receiving treatment showed some indications of improved social competence and better friendships when compared with those not receiving treatment. Participants receiving treatment also showed indications of less loneliness. The ability to recognize different emotions was measured in two studies and there was no evidence that it was improved by taking part in a social skills group. Social communication as it relates to idiomatic expressions was only reported in one study and no significant differences between treatment and control group were found. Nor was there evidence of a beneficial effect of social skills groups on parental or child depression. No adverse effects were reported in the studies. Limitations of this review include a small number of studies and participants, and a high risk of bias due to parents knowing whether their child was in the intervention group or not. The studies focused mainly on children with ASD aged 7 to 12 with average or above average intelligence, and they were all carried out in the US.
We searched for studies of audio-visual informed consent interventions which allocated people to an experimental or control group by a random or quasi-random process, published up until June 2012. We found 16 studies, involving a total of 1884 people. Nine studies included people considering real clinical trials, eight included people asked to imagine participating in a clinical trial (a hypothetical trial), with one including both. Most of the studies were conducted in the United States. People were considering (or imagined considering) participation in a range of different clinical trials, including those testing cancer treatments and drugs for mental health problems. The audio-visual informed consent information was presented on computers, DVDs, videos and CD-ROMs. They included voice overs by professional actors, real patients talking about their experiences and a combination of words, pictures and audio to explain the technical concepts. In some studies, people also received the usual written informed consent forms and/or a face-to-face explanation by the study staff. There is low to very low quality evidence that audio-visual consent interventions may slightly improve knowledge or understanding of the parent trial, but may make little or no difference to rate of participation or willingness to participate. Audio-visual presentation may improve participation satisfaction with the information provided. However its effect on satisfaction with other aspects of the process is not clear. There is not enough evidence to draw conclusions about anxiety arising from audio-visual informed consent. There is conflicting, very low quality evidence about whether audio-visual interventions take more or less time to administer, and no study measured researcher satisfaction with the informed consent process, nor ease of use. We do not believe that any studies were funded by organisations with a vested interest in the results. The quality of evidence from real clinical trials was low, and from hypothetical clinical studies, very low. This is because of the small number of people in the studies, and some issues in the way they were conducted. If the next update of this review includes more studies of audio-visual informed consent presentation, it could change the results of this review.
We assessed the the quality of evidence for many outcomes including cardiac-related rehospitalisation as low or very low because variability among studies (heterogeneity) was high, a range of confidence intervals was wide, and random sequence generation and blinding of participants and personnel were poorly described. The effect of PAP therapy on all-cause mortality was uncertain. In addition, although PAP therapy did not reduce the risk of cardiac-related mortality and rehospitalisation, there was some indication of an improvement in quality of life score for heart failure patients with CSA. Furthermore, the evidence was insufficient to determine whether adverse events were more common with PAP than with usual care. These findings were limited by low- or very low-quality evidence. PAP therapy may be worth considering for individuals with heart failure to improve quality of life.
The evidence in this review is up-to-date as of 25 February 2019. We included 35 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 1474 participants, which tested several different corticosteroids, mostly delivered topically (on the skin). Corticosteroids were compared with one of the following: a placebo (a treatment that resembled the corticosteroid but had no active ingredient); a medicine from a category called calcineurin inhibitors; another medicine type; another corticosteroid or mode of delivery; the same corticosteroid plus an extra treatment; or an alternative treatment. Treatments were given for between one week and six months, with side effects measured throughout the treatment, and pain and healing measured at the end of treatment. Results from two studies showed that topical corticosteroids (e.g. clobetasol propionate, flucinonide, betamethasone and triamcinolone acetonide), when applied to the mouth in a sticky cream, may be effective in reducing and stopping pain. We do not have the evidence that topical corticosteroids can eliminate the oral lichen planus lesions, and we are uncertain about side effects. We found no consistent evidence that any particular corticosteroid was better than any other. Three studies using another topical medicine called tacrolimus (a calcineurin inhibitor) found that this medicine may be more effective than corticosteroids, but may be more likely to cause mild side effects. Available evidence comparing corticosteroids with other treatments is very limited. The reliability of most of the evidence is very low, so we cannot be sure about the findings and future research may lead us to different conclusions. The available evidence suggests that topical corticosteroids may be effective for treating painful oral lichen planus, but our confidence in these findings is limited as there were only a small number of studies and participants. There is some evidence that tacrolimus may be more effective than a corticosteroid, but evidence on negative side effects is inconclusive.
We identified two randomised controlled trials with 581 women requiring augmentation, each looking at different doses of oral misoprostol compared with oxytocin. One study gave 20 mcg doses of misoprostol every hour up to four hours, after which the dose was increased; the second gave women 75 mcg doses, repeated after four hours provided there were no adverse effects observed. Neither trial reported on the important safety outcomes of maternal or neonatal deaths, or severe maternal ill health. One trial measured duration of labour from the start of augmentation, which was slightly shorter with intravenous oxytocin (5.20 hours compared with 5.22 hours). The number of vaginal deliveries within 12 and 24 hours, and caesarean section rates were similar. Neither trial reported clearly higher rates of uterine hyperstimulation with worrying fetal heart rate changes in the titrated oral misoprostol group. The rates of this outcome in the two studies varied greatly however. The evidence on uterine hyperstimulation without fetal heart rate changes was not consistent. The number of women reporting nausea, vomiting, shivering and pyrexia was low with both misoprostol and oxytocin. Maternal satisfaction was not reported in either trial. Important uncertainties still exist on the safety and acceptability of titrated oral misoprostol for labour dystocia, and further research is needed before it can be recommended as an alternative to oxytocin. However, in facilities that do not have access to electronic oxytocin infusion, lower doses of titrated misoprostol may be a better alternative to avoid hyperstimulation.
The evidence identified from our literature search is current to May 2017. Four randomized controlled studies met the inclusion criteria for this review (involving 256 adults). One more study is awaiting classification. These studies were conducted in adult surgical and mixed medical-surgical ICUs, and compared BIS monitoring with various measures for CA. For one study, the BIS monitoring devices manufacturer provided equipment. The company had no role in the conduct of the study. Another study was funded as part of a scientific and technological project. No funding information was available for the other two studies. With BIS monitoring, we found no significant differences in ICU length of stay (one study, 50 adults), duration of ventilation (two studies, 155 adults) and the risk of adverse events (one study, 105 adults) compared with CA. Clinically relevant adverse events, for example, accidental self-removal of the breathing tube, were not reported. We could not measure combined difference in amount of sedative use because of the different sedation protocols and sedatives used. None of the other outcomes of interest for the review, for example, death, ventilator-associated pneumonia, quality of life etc. were reported in any of the studies. The findings of our review are from a limited number of studies which provided 'low to very low' GRADE quality of evidence. The authors of this review conclude that we found insufficient evidence about the effects of BIS monitoring compared with CA of sedation in critically ill adults who were on a ventilator.
Studies have shown that workplaces providing services to help smokers to stop smoking have been effective. Services can include providing nicotine replacement therapy (NRT) and counselling support to help smokers quit. However, it is not known if policies that stop people smoking in institutions are effective. Whilst smoking is banned in many public places, it is not banned in all of them. Smoking is allowed in some healthcare organisations, universities and prisons. Study characteristics We searched for studies that measured whether introducing a smoking policy or ban, in hospitals, universities or prisons, reduced secondhand smoke exposure and helped people to quit smoking. The study could be in any language. It had to report information on health and smoking before the policy or ban started and for at least six months afterwards. We have included 17 studies in this review. Twelve studies provide evidence from hospitals, three from prisons and two from universities. The evidence is up-to-date to June 2015. Key results We grouped together 11 of the included studies, involving 12,485 people, and found that banning smoking in hospitals and universities increased the number of smoking quit attempts and reduced the number of people smoking. In prisons, there was a reduction in the number of people who died from diseases related to smoking and a reduction in exposure to secondhand smoke after policies and bans were introduced, but there was no evidence of reduced smoking rates. Quality of the evidence We found no relevant high-quality studies to include in our review. Future high-quality research may lead to a change in these conclusions and it is not possible to draw firm conclusions from the current evidence. We need more research from larger studies to investigate smoking bans and policies in these important settings.
We found that there were several comparative studies, but these involved a relatively small number of patients. There was evidence that botulinum toxin improves the symptoms of OAB. It was unclear what the best dose of botulinum toxin was. Botulinum toxin injections into the bladder appeared to give few side effects or complications, but there were no long-term follow-up studies, and there could be rare side effects that have not been discovered yet.
The evidence is current to June 2016. Of the 21 included trials including 1420 participants, 14 trials compared a probiotic with placebo or no treatment and seven trials compared a probiotic with lactulose. The treatment duration of the trials ranged from 10 days to 180 days. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but may lead to little or no difference in mortality. Probiotics may slightly improve quality of life when compared with no intervention; however, this conclusion is based on three trials with low-quality evidence. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence was very low. There were no reports of septicaemia attributable to probiotic in any trial. There was no evidence of more adverse events with probiotics when compared to placebo or lactulose. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. Many of the included trials suffered from a high risk of systematic error (‘bias’) and a high risk of random error (‘play of chance’). Accordingly, we consider the evidence to be of low quality. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence was very low. High-quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics.
We included eight clinical studies. Four studies reported on interventions for patient–caregiver relationship and four studies were aimed specifically at improving caregiver well-being. We found five ongoing studies. The interventions tested were diverse in nature (e.g. cognitive behavioural therapy (talking therapy); psychoeducation (providing education and information to people seeking or receiving mental health services); coping skills training; self-management; social network intervention); and delivery (e.g. face-to-face; web-based), and all studies were relatively small (included between 13 and 56 neuro-oncology caregivers). We found some evidence for positive effects of caregiver support on psychological distress, feelings of mastery (i.e. the feeling of being in control of the caregiving situation), and quality of life. None of the studies reported effects on caregiver burden or quality of patient–caregiver relationship. None of the studies measured caregiver physical well-being. Overall, the certainty of the evidence was low to very low, which means the true effect of caregiver support may be substantially different. Our findings suggest it is not currently possible to draw definitive conclusions about the effectiveness of supportive interventions to improve neuro-oncology caregiver well-being. More high-quality research is needed on support for family caregivers of patients diagnosed, and living, with a brain or spinal cord tumour.
The aim of the present review was to evaluate the evidence from randomised controlled trials for the efficacy and acceptability of antidepressant treatment in acute AN. Seven small studies were identified; four placebo-controlled trials did not find evidence of efficacy of antidepressants in improving weight gain, eating disorder or associated symptoms, as well as differences in completion rates. Meta-analysis of data was not possible for most outcomes. However, major methodological limitations of these studies (e.g. insufficient power to detect differences) prevent from drawing definite conclusions or recommendations for antidepressant use in acute AN. Further studies testing safer antidepressants in larger and well designed trials are needed to guide clinical practice.
We searched differing databases of published research for all papers relating to the accuracy of IQCODE for detecting dementia. We found only one study that tested diagnostic accuracy of IQCODE in a primary care/general practice setting. The study was of a select population (Japanese Americans) and the results may not be applicable to patients in other countries. We also noted issues in the study methods used and the reported results. Based on this single study we are unable to give guidance on how well IQCODE may function as a dementia assessment in primary care. More research is needed in this area as many patients with memory or thinking problems will first consult their general practitioner / family doctor.
We identified one study, which recruited 64 adults with type 2 diabetes and schizophrenia or schizoaffective disorder. Researchers compared usual care plus information leaflets with a 24-week education programme delivered once a week for 90 minutes (Diabetes Awareness and Rehabilitation Training). This programme provided basic diabetes education and information about nutrition and exercise. The average age of participants was 54 years; participants had been living with type 2 diabetes for on average nine years and with their psychiatric diagnosis since they were on average 28 years old. People in the included study were monitored for six months after the programme ended. This evidence is up to date as of 07 March 2016. In summary, few studies have evaluated the effects of diabetes self management programmes for adults with severe mental illness. Study authors of the single included study did not report diabetes-related complications, all-cause mortality, adverse events, health-related quality of life nor socioeconomic effects. They described small improvements in body mass index and body weight, as well as in diabetes knowledge and self efficacy. Current evidence is insufficient to show that these types of programmes can help people with type 2 diabetes and severe mental illness to better manage their diabetes and its consequences. We rated the overall quality of the evidence as very low, mainly because of the small numbers of included studies and participants, and because reported study results showed inconsistency.
We included one trial with very low-quality evidence and involving 14 preterm infants. The search is up to date as of February 2018. Addition of extra fat to human milk for preterm infants showed no clear benefits with regards to short-term rates of weight gain, length gain, and head growth. There was no evidence that the extra fat increased the risk of feeding intolerance. No data were available regarding the effects of addition of extra fat on long-term growth, body fat, obesity, high blood sugar, or brain development. There were also limited data to assess side effects. There was insufficient high-quality evidence on the benefits and harms of the addition of extra fat to human milk in preterm infants, and no long-term outcomes have been reported. Since addition of extra fat to human milk is currently done as part of multi-nutrient fortification, future trials should evaluate the effect of the fat component on short- and long-term growth, body fat, obesity, high blood sugar, or brain development. The right amount and composition of extra fat needed, side effects, and delivery practices should also be evaluated.
This review examined the impact of different payment systems on primary care physician behaviour. Three payment systems were included: capitation (payment is made for every patient for whom care is provided), salary, and fee for service (payment is made for every item of care provided). There was some evidence that primary care physicians provide a greater quantity of primary care services under fee for service payment compared with capitation and salary, although long-term effects are unclear. There was no evidence, however, concerning other important outcomes such as patient health status, or comparing the relative impact of salary versus capitation payment.
We identified randomised, double-blind, placebo controlled trials of specific allergen immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Fifty-one studies satisfied our inclusion criteria. In total there were 2871 participants (1645 in the treatment groups and 1226 in the placebo), each receiving on average 18 injections. The duration of treatment varied from three days to three years. This review has shown that injection immunotherapy in suitably selected patients with hay fever results in significant reductions in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events and no fatalities.
We obtained updated evidence for this review from 11 randomised controlled studies comparing a nasogastric tube with PEG in a total of 735 patients. Seven studies measured treatment failure i.e. feeding interruption, blocking or leakage of the feeding tube in 408 patients randomised to either a nasal gastric tube or PEG. The studies showed a higher probability of treatment failure with a nasal gastric tube. The number of deaths was no different with the two methods; nor was the overall occurrence of adverse events. Participants with PEGs may have a better quality of life. Possible limitations of this review include the small number of participants in the majority of studies, explained by the high cost of PEG and requirements for endoscopy in its use, the operational challenges to accomplish a clinical trial in this area and the different length of follow-up of the patients in the studies (from less than four weeks to six months). There were clinical differences between the trials, with the participants having different baseline diseases and different techniques used to insert the PEG. The findings of the present review of the literature should be interpreted with caution, given that there were methodological issues with most of the included studies which increase the risk of bias in the trial. This systematic review of the literature is valuable in analysing 11 studies, with a sample size of 735 patients. Nevertheless, further randomised clinical trials that adopt a rigorous method are warranted.
We included adults (aged 18 years and above) admitted for any type of upper abdominal surgery. The evidence is current to August 2013. We found 12 studies with a total of 1834 participants. The maximum period of time that a patient was followed by the doctor was seven days postoperatively. The quality of the included studies was uncertain because of poor reporting in the published articles. The following results were examined in this review: clinical complications, respiratory failure (that is, inadequate gas exchange by the respiratory system), and pulmonary complications. The results from participants receiving IS were the same as for those receiving either no treatment, deep breathing exercises (DBE) or physiotherapy in the meta-analyses for clinical complications, respiratory failure, and pulmonary complications. Because of poorly conducted studies (results not similar across studies; some issues with study design and; not enough data collected and organized) we ranked the overall quality of the evidence reported in this review as low. There is low quality evidence showing a lack of effectiveness of incentive spirometry for prevention of postoperative pulmonary complications in patients after upper abdominal surgery. This review underlines the urgent need to conduct well-designed trials in this field.
We searched scientific databases for clinical studies of people of any age with low platelet counts requiring a lumbar puncture or epidural anaesthesia. The evidence is current to 13 February 2018. In this review, we found only three cohort studies. Only two of these studies reported outcomes relevant to this review. Both studies included people with low platelet counts and blood cancer; one included 21 adults and the other included 129 children. Both studies compared people who had and had not received platelet transfusions before the insertion of a lumbar puncture needle. No studies assessed the use of platelet transfusions prior to insertion of an epidural catheter or different platelet count thresholds for platelet transfusion administration prior to a procedure. There were no major procedure-related bleeding complications in either study. No serious adverse events occurred in the one study (21 participants) that reported this outcome. There was little or no difference in the number of minor bleeding complications in either adults or children who received or did not receive platelet transfusions. None of the studies reported on death, number of platelet transfusions given after the procedure, length of hospital stay, or quality of life. The quality of the evidence from the included studies was very poor. We found no evidence from randomised controlled trials to answer our review question. A study would need to be designed with at least 47,030 participants to be able to detect an increase in the number of people who had bleeding after lumbar puncture or epidural anaesthetic from 1 in 1000 to 2 in 1000. A study that uses routinely collected electronic medical records (big data) is likely to be the only study design that could answer our review question.
We included a total of 11 studies recruiting 5862 apparently healthy adults in this review. The findings of the review indicate that using technologies to support adults' attempts to become more active, achieve the recommended weekly amounts of activity, or become fitter are successful. Changes can be achieved with help from a trained professional and through personal support via telephone, e-mail, or written information. New physical activity can be maintained for at least one year and it does not increase the risk of falls or exercise related injuries. More research is needed to establish which methods of exercise promotion encourage specific groups of people to be more physically active in the long term.
In September 2016 we searched for clinical trials in which antiepileptic drugs were used to treat chronic pain. We found two studies with a total of 141 participants (aged 7 to 18 years) with chronic neuropathic pain, complex regional pain syndrome type 1, or fibromyalgia, which they had for more than 3 months. One study looked at pregabalin versus placebo for people with fibromyalgia, and found no significant change in pain scores. The other study evaluated gabapentin compared to amitriptyline, but did not report our specified pain outcomes. Side effects were uncommon, and only mild reactions (such as nausea, dizziness, drowsiness, tiredness, and abdominal discomfort): pregabalin 38 participants, gabapentin 2 participants, amitriptyline 1 participant, and placebo 34 participants. Only 11 participants withdrew due to these mild side effects (4 pregabalin, 2 gabapentin, 1 amitriptyline, 4 placebo). We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The available evidence in this review was of very low-quality due to a lack of data and small study sizes.
Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth.
We found 30 randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) with 9177 participants. The duration of the interventions ranged from 1 week to 12 months and follow-up after treatment from 0 to 12 months. Most studies took place in community settings, almost all in high-income countries and two each in Asia and Latin America. The studies included a wide spectrum of interventions and were both individual- and group-based. Psychological interventions have a small and positive effect on confidence for self-care and glycosylated haemoglobin A1c (HbA1c - a long-term measure of glucose control) in adults with type 2 diabetes. Compared to usual care, psychological interventions showed no firm effect on diabetes-related distress, health-related quality of life, death from any cause, adverse events or blood pressure levels. No study reported on diabetes-related complications (like stroke, heart attacks or kidney impairment) or socioeconomic effects (such as absence from work or costs for medication). This evidence is up to date as of 21 September 2016. Overall, the quality of the evidence was low because of small studies, missing data, and limitations in the design and implementation of the included studies. Four studies are awaiting further assessment, and 18 studies are ongoing with results hopefully be published in the near future.
This review found that while initial treatment with chemotherapy rather than endocrine therapy may be associated with a higher response rate, the two initial treatments had a similar effect on overall survival. No single group of patients who might benefit from or be harmed by one treatment over the other were identified, although there was little information to address this question. Six of the seven fully published trials commented on increased toxicity associated with chemotherapy including nausea, vomiting and alopecia. Three of the seven trials mentioned aspects of quality of life but their findings provided differing results. Only one trial formally measured quality of life (QOL), concluding that QOL was better with chemotherapy. Based on these trials, no conclusions can be made as to the QOL achieved with either treatment. Accurate information about hormone receptor status is now routinely available for many women with metastatic breast cancer, and hormonal treatments have improved in their effectiveness in the last 10 years. In women with metastatic breast cancer where hormone receptors are present, a policy of treating first with endocrine therapy rather than chemotherapy appears to be better, on the basis of the trials and outcomes in this review, except in the presence of rapidly progressive disease.
The main aim of this review was to find out whether pentoxifylline compared with placebo (an inactive drug) or no drug offers important advantages to babies born early. Only one study of moderate size and quality was identified in this review. This study did not show strong evidence that pentoxifylline offers important advantages to babies born early. We have therefore been unable to determine the effects of pentoxifylline in preventing long-lasting breathing problems in babies born early. Future high-quality studies are needed to answer this question.
The review authors searched the medical literature up to March 3 2015, and identified three relevant clinical trials (212 participants) that investigated ozone therapy for the treatment of foot ulcers in people with diabetes. The available evidence was of low quality. One trial, with 101 participants, compared ozone treatment with antibiotics and followed up for 20 days. The results of this study showed that the reduction in ulcer size was greater, and also the length of hospital stay was shorter, in those receiving ozone treatment, but there was no apparent benefit in terms of the number of foot ulcers healed. No adverse effects (side effects or harms) were observed with either treatment. The other two trials (111 participants) compared ozone treatment plus usual care with usual care. The results of these two studies showed that there were no apparent differences between the groups for reduction in ulcer size,the number of foot ulcers healed, or occurrence of adverse events and amputation rates. Quality of life was not reported by either trial. On the basis of the limited and poor quality information available, the review authors were unable to draw any conclusions about the effectiveness of ozone therapy for treating foot ulcers in people with DM.
We included eight studies (899 adults and children with SCD (HbSS, HbSC or HbSβºthal genotypes)). Studies lasted from six to 30 months. In four studies, 577 adults and children with SCD were randomly selected to receive hydroxyurea or placebo. In two studies, 254 children with SCD, who were also at an increased risk of having a first or second stroke, were randomly selected to receive hydroxyurea and phlebotomy (collection of blood) or blood transfusion and chelation (administration of agents to remove excess iron from the body). These six studies only recruited people with HbSS or HbSβºthal genotypes so results do not apply to people with the HbSC genotype. There was moderate quality evidence from these six studies that those receiving hydroxyurea experienced significant reductions in the frequency of pain crises, increases in fetal haemoglobin and decreases in neutrophil (white blood cell) counts compared to the comparator treatment. There was no difference between people receiving hydroxyurea or other treatments in terms of quality of life, deaths during the studies and side effects (including serious and life-threatening side effects); however, there is less information about these outcomes in the studies, so the quality of this evidence is low. Two further studies were included in the review. In one study, 22 children with SCD, who were also at an increased risk of having a stroke, were randomly selected to receive hydroxyurea or no treatment (observation only) and in one study 44 adults and children were randomly selected to receive treatments with or without adding hydroxyurea. Both studies showed an increase in fetal haemoglobin for people receiving hydroxyurea compared to the comparator treatment and there were no deaths during the studies. There was no difference between people receiving hydroxyurea or other treatments in terms of pain crises and side effects (including serious or life-threatening side effects) and these studies did not measure quality of life. The quality of the evidence from these studies is very low, given the studies were very small and only recruited around 20% of the intended number of people and results do not apply to all people with SCD (different genotypes). The evidence shows that hydroxyurea is likely to be effective in the short term at decreasing the frequency of painful episodes and raising fetal haemoglobin levels in the blood in people with SCD. Hydroxyurea is also likely to be effective in preventing first strokes for those at an increased risk of stroke and does not seem to be associated with an increase in any side effects (including serious and life-threatening side effects). There is currently not much evidence on whether hydroxyurea is beneficial over a long period of time, what the best dose to take is, or whether treatment causes any long-term or serious side effects. More studies are needed to answer these questions.
This review included one study of 100 people aged between 6 and 57 years old. The study compared an inhaled antibiotic called aztreonam to placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly (by chance). The study lasted 52 weeks. The only study included in this review found inhaled aztreonam had no beneficial effect on lung function or rates of chest infections in people with cystic fibrosis and Burkholderia cepacia complex infection. There was no difference between groups in relation to the average time to the next exacerbation or the number of people hospitalised for an exacerbation. Overall adverse events were similar between groups and with regards to other outcomes assessed, there was no difference between treatment groups for mortality, quality of life or sputum density. More research is needed to establish if other inhaled antibiotics may be useful. Overall quality of evidence was considered to be moderate across all outcomes, which means further research is likely to have an important impact on results.
We found 160 randomized controlled trials with 54,109 participants. Eighteen studies with 36,034 participants contributed evidence about devices and drugs to prevent premature waking up during surgery. Nine studies compared anaesthetic depth monitoring versus other methods to adjust drugs. Nine studies compared different drugs. There are 10 studies awaiting classification, which we will process when we update the review. In the largest studies of anaesthetic depth monitors (five studies with 31,181 participants) there were 152 participants with possible or definite awareness (recall of surgery events after surgery). The use of anaesthetic depth monitors to adjust drugs during anaesthesia may have similar effects on the risk of awareness when compared with standard clinical and electrical monitoring. Wakefulness is reduced by ketamine and etomidate compared to thiopental. Benzodiazepines reduces awareness compared to thiopental, ketamine, and placebo. Also higher doses of inhaled anaesthetics versus lower doses reduced the risk of awareness. The quality of the evidence was low or very low because the studies the results were not similar across studies, and there were not enough data.
We found three small studies, with a total of 20 people (11 adults and 9 children). The studies had a cross-over design (participants received the study interventions in a random order, and served as their own control) and looked at the effect of different head positions. Researchers measured the pressure inside the skull (intracranial pressure (ICP)) and the pressure gradient causing blood flow to the brain (cerebral perfusion pressure (CPP)). Two studies were funded by research grants from the national Department of Health, and one study received no funding. At the time of follow-up 28 days following hospital admission, one child had died. None of the studies assessed quality of life, Glasgow Coma Scale (a measurement of how conscious someone is), or disability. The studies gave varied results and our certainty in the results is very low, so we do not consider the body of evidence to be reliable. None of the studies found any evidence of a change in CPP due to different backrest positions. The results for ICP were more mixed but there is still no convincing evidence that HBE changes ICP. There is insufficient evidence to say whether the intervention is safe. One child experienced an increase in ICP in response to the intervention, which resolved when the height of the bed was returned to the normal position. We are uncertain about the effects of different backrest positions in people with serious brain injury. The body of evidence for this research question is very low due to variability in physiological response in the study participants, unclear risk of bias in the study methods, and the small number of people enrolled in each study. We are uncertain about the effects of different backrest positions in people with serious brain injury. Well-designed and larger trials are needed. Trials also need to measure the right patient outcomes over a longer period of time in order to understand how and when different backrest positions can affect people with brain injury.
We included six studies in this review, with 1176 adolescents overall. The mean age of adolescents was 16.9 years. We were interested in studies with short-, medium-, and long-term follow-up periods to assess whether any effects were due to the brief intervention. The studies compared brief intervention programmes with two major kinds of comparison or control groups: 1) an information provision only (general health promotion materials and harm reduction information) group and 2) an assessment-only group, where adolescents received no intervention but were evaluated on substance use and other behaviour at follow-up appointments at different time periods following delivery of the intervention. Three studies with 732 adolescents compared brief interventions with information provision only, while the other three, with 444 adolescents, compared brief interventions with assessment only. Trials were either conducted in the United States or the United Kingdom. Delivery of the interventions was individual or group face-to-face feedback across high schools and further education colleges. All interventions were up to four sessions in length. Our primary outcome was abstinence or reduction of substance use behaviour, and our secondary outcomes were engagement in criminal activity related to substance use and engagement in delinquent-type behaviours related to substance use. For outcomes that concern substance use, the studies assessed use of alcohol and cannabis. When compared to information provision, brief interventions are probably not more efficacious in reducing substance use or delinquent behaviour. When compared to assessment-only controls, the interventions may have some significant effects on substance use and behaviours. At short-term follow-up, brief interventions significantly reduced cannabis frequency in one study. At medium-term follow-up, brief interventions significantly reduced frequency of alcohol use, alcohol abuse and dependence symptoms, and cannabis abuse symptoms in one study. At long-term follow-up, brief interventions significantly reduced alcohol abuse, cannabis frequency, and cannabis abuse and dependence symptoms in one study. The pattern of results indicates that adolescents who received a brief intervention generally did better in reducing their alcohol and cannabis use than adolescents who received no intervention at all. However, adolescents who received a brief intervention did not seem to do better in reducing their alcohol and cannabis use than adolescents who received information-only interventions. It is therefore premature to make definitive statements about the effectiveness of brief school-based interventions for reducing adolescent substance use. Overall, the evidence was of moderate or low quality, with two outcomes found to have very low quality of evidence. There were three major issues across the studies: 1) there was no blinding of adolescents, 2) there was uncertainty as to whether participant allocation to study groups was concealed, and 3) a small total number of adolescents and number of events. None of the included studies reported information about funding source or conflicts of interest.
Although there are many published studies about treatment of Gaucher disease, those that are based on randomized controlled clinical studies are considered to provide the strongest evidence. Eight such studies (300 participants) were identified by systematically reviewing the medical literature. Potential risks of bias in the methods employed in the original studies and in the data reported were assessed; only one study scored 'low' in all bias domains. Six evaluated the possible beneficial effects on the disease by enzyme replacement therapy using different products, doses or frequencies of administration; two studies examined the effects of substrate reduction therapy. Owing to different study methods and data formats, the original results could not be pooled or combined in order to obtain summary measures of efficacy. Our analysis, despite being limited by the small number of studies, suggests that, at least during the first year of treatment, different enzyme replacement therapy drugs appear to have a similar safety profile and all improve some of the most obvious manifestations of the disease. One randomized controlled study assessing substrate reduction therapy was published immediately prior to producing the final version of this review, and this, along with a further ongoing study (expected to be published in the near future), will be assessed for eligibility in a future update of the review.
Only randomised controlled trials were included in this review. In these studies,a group of participants were given physiotherapy intervention and were compared with another group of participants, who did not receive physiotherapy. Participants were assigned to a group in random fashion so a fair test was established. Thirty-nine randomised trials involving 1827 participants were identified as suitable for this review. The quality of the trials was not high because in many, methods were not reported adequately and blinding was not feasible. These trials assessed various physiotherapy interventions, so the trials were grouped according to the type of intervention being used (i.e. general physiotherapy, exercise, treadmill training, cueing, dance, or martial arts). Improvement in all walking outcomes (except the 10- or 20-metre walk test) was noted with physiotherapy intervention. However, these improvements were significant only for walking speed, walking endurance, and freezing of gait. Mobility and balance also improved with a physiotherapy intervention, with significant improvements reported in one test of mobility (the Timed Up & Go test, which times how long it takes a person to get up from a chair, walk a certain distance, then walk back to the chair and sit down) and in two tests of balance (one assessing how far a person can reach before he or she loses balance (Functional Reach Test) and another assessing multiple aspects of balance (Berg Balance Scale)). Clinician-rated disability, using the Unified Parkinson’s Disease Rating Scale (UPDRS), was also improved with physiotherapy intervention. No difference was observed between the two groups in falls or patient-rated quality of life. One study reported that adverse events were rare; no other studies reported data on this outcome. When the different physiotherapy interventions were compared, no evidence suggested that treatment effect differed across the physiotherapy interventions for any of the outcomes assessed. This review provides evidence of the short-term benefit of physiotherapy for the treatment of PD. Although most observed differences were small, improvements in walking speed, balance with the Berg Balance Scale, and clinician-rated disability using the UPDRS were of a size that patients may consider them to be important. These benefits should be interpreted with caution because of the quality of the included trials, and the lack of common assessment of treatment effects. This affected the quantity of data that we could use for analysis.
Therefore we reviewed studies of interventions to improve older people's involvement in their care. There has been little research in this area involving older people as the main target of the research. Only three trials were identified. These evaluated the effects of written or face-to-face preparation for consultations with doctors. Interventions of a pre-visit booklet and a pre-visit session (either combined or pre-visit session alone) led to more questioning behaviour by older people and more self-reported active behaviour. Overall, there is sparse evidence about the effects of interventions for improving older patients' involvement in their primary care.
We included four studies; three compared the two approaches to resuscitation when given by untrained bystanders under instruction by telephone. One study compared the two approaches when given by EMS personnel. The three studies, comparing the approaches given by untrained bystanders, (3737 participants) were all undertaken in urban areas and some included both children and adult OHCA. The, bystanders were all untrained and given telephone instructions from the emergency services. The fourth study compared approaches given by EMS professionals (23,711 participants); it was undertaken in urban areas and included only adult OHCA. When CPR was performed by bystanders, we found that more people survived until discharge from hospital after chest compression alone than they did following interrupted chest compression with pauses at a fixed ratio for rescue breathing (15 compressions to 2 breaths) (14% versus 11.6%). For the outcomes of survival to hospital admission and neurological outcomes, we did not have sufficient data to be certain that either strategy was better. No data was available for adverse effects, quality of life or survival at one-year. When CPR was performed by EMS professionals, we found that survival to hospital discharge was slightly lower with continuous chest compressions (100/minute) plus asynchronous rescue breathing (10/minutes) CPR compared with interrupted chest compression plus rescue breathing. Around 9.7% of people lived when they received interrupted chest compression plus rescue breathing compared with 9% of people who received continuous chest compression plus asynchronous rescue breathing. The number of people who survived to hospital admission was slightly higher in those treated with interrupted chest compression plus rescue breathing compared with continuous chest compression plus asynchronous rescue breathing (25.9% versus 24.6%). There was little or no difference in neurological outcomes. The proportion of people who experienced adverse events was probably similar with 55.4% people treated with interrupted chest compression plus rescue breathing experiencing an adverse event compared with 54.4% in those treated with continuous chest compression asynchronous rescue breathing. For bystander-provided CPR, the quality of the evidence was high for the outcome of survival to hospital discharge. For survival to hospital admission, one trial provided results and the evidence was of moderate-quality because of low numbers of people for whom data were available. This was also the case for neurological outcomes. In the one EMS professional-provided CPR trial, the quality of the evidence was moderate for the outcome of survival to hospital discharge because the results do not exclude there being little or no difference between the two approaches, and this is also the case for adverse events. For survival to hospital admission there was high-quality evidence. The main limitation of the current evidence is that only a few trials have been undertaken, and for some outcomes, not enough data have been generated.
We have reviewed 29 studies in 5489 patients with depression that compared treatment with extracts of St. John's wort for 4 to 12 weeks with placebo treatment or standard antidepressants. The studies came from a variety of countries, tested several different St. John's wort extracts, and mostly included patients suffering from mild to moderately severe symptoms. Overall, the St. John's wort extracts tested in the trials were superior to placebo, similarly effective as standard antidepressants, and had fewer side effects than standard antidepressants. However, findings were more favourable to St. John's wort extracts in studies form German-speaking countries where these products have a long tradition and are often prescribed by physicians, while in studies from other countries St. John's wort extracts seemed less effective. This differences could be due to the inclusion of patients with slightly different types of depression, but it cannot be ruled out that some smaller studies from German-speaking countries were flawed and reported overoptimistic results. Patients suffering from depressive symptoms who wish to use a St. John's wort product should consult a health professional. Using a St. John's wort extract might be justified, but important issues should be taken into account: St. John's wort products available on the market vary to a great extent. The results of this review apply only to the preparations tested in the studies included, and possibly to extracts with similar characteristics. Side effects of St. John's wort extracts are usually minor and uncommon. However, the effects of other drugs might be significantly compromised.
This review examined the studies to date to see what effect psychological treatments had on women with metastatic breast cancer. We found 10 studies with a total of 1378 women with metastatic breast cancer. Three of the studies used a psychological treatment known as cognitive behavioural therapy (CBT), four studies used supportive-expressive group therapy (SEGT), while the remaining three studies used treatments that were delivered on an individual basis and were neither CBT nor SEGT. We performed statistical analysis and found that the odds ratio (a measure of association between an intervention and an outcome) for survival of women with metastatic breast cancer one year after receiving psychological treatment was 1.46, suggesting that there was an association between the psychological treatment and improved survival. This finding was not found when looking at the odds ratio of survival at five years. We also found some evidence that psychological treatments in the short term (for example, one year) may produce a small reduction in pain and improve some psychological symptoms. However, making comparisons across these studies was difficult as they differed in their conduct, treatments and measures used. Moreover, we cannot rule out that the psychological treatments could also cause psychological harm.
Based on eight randomised clinical trials of high risk of bias, the administration of ursodeoxycholic acid to patients with primary sclerosing cholangitis did not significantly reduce mortality, hepatic decompensation, need for liver transplantation, liver histological deterioration, or radiological deterioration compared with placebo or no intervention. The use of ursodeoxycholic acid showed a statistically significant improvement of liver biochemistry. However, evidence of these beneficial effects is weak as it is produced from trials with high risk of bias and a rather small number of patients. Furthermore, these observations are at risk of outcome measure reporting bias as half or less than half of the trials reported on these outcomes. One trial assessed the self-estimated quality of life of patients with primary sclerosing cholangitis treated with ursodeoxycholic acid. No significant difference was found in any of the studied components, physical as well as mental. Based on an analysis of six of the eight included trials, the use of ursodeoxycholic acid seemed safe and well tolerated, without reports of serious adverse events. We were unable to identify trials evaluating other bile acids for patients with primary sclerosing cholangitis. Accordingly, the evidence does neither support nor refute bile acids for primary sclerosing cholangitis.
We (a team of Cochrane researchers) wanted to see whether lifestyle interventions have a beneficial effect on any type of urinary incontinence in adults We searched the medical literature extensively up to July 2013 for studies that compared the effects of community-based lifestyle alterations with either no treatment, or other non-surgical treatments, or medical (medicine) treatment, on urinary incontinence in adults. We identified 11 studies, with 5974 participants (nearly all women, only 20 were men), that investigated the effect of lifestyle alterations on urinary incontinence. Four investigated weight loss; one compared a soy-rich diet with a soy-free diet; three investigated changes in volume of fluid intake; and three investigated the effect of reducing caffeine intake. We identified no trials that investigated reducing alcohol intake, avoiding constipation and straining, stopping smoking or levels of physical activity. Findings from four studies suggested that weight loss may reduce incontinence among overweight women and this merits further research. However, it should be noted that a large proportion of the participants contributing to this result were part of two diabetes studies that, while they recorded the effect of weight loss on urinary incontinence, did not record how many participants suffered from it at the start of the study. The duration of the weight loss programmes in these studies ranged from three to 12 months. A small amount of very low quality evidence from the studies that investigated volume of fluid intake suggested that symptoms of urinary incontinence may reduce when fluid intake is reduced, although some participants in the studies reported headaches, constipation or thirst. We could not combine the findings from other studies that investigated a similar treatment (e.g. caffeine reduction) because they measured their results in different ways, and/or were of poor quality, which means their results may be unreliable. Much more well-designed research is needed, so that lifestyle recommendations for the treatment of incontinence can be based on good evidence. At present there is not enough evidence to establish whether any lifestyle treatments work.
we identified only one poorly designed study for inclusion. we found that giving calcium to newborn infants raised blood calcium levels immediately after EBT while blood calcium was reduced among newborn infants who did not receive calcium during EBT. However, despite the observed trends in the values of blood calcium in both groups of the study, the average values of blood calcium in both groups remained within normal limits. In addition, the information available for this review was limited as the effects of giving or not giving calcium during EBT was not studied beyond the time of EBT. based on the findings in this review, there is no good-quality evidence to support or reject continual use of calcium during EBT. We are unable to make conclusions, as the evidence that we found is limited and of very low quality and could change if more results from larger and better-designed studies become available.
This review looked at whether these medicines could help patients with problems caused by cancer treatments. Eight studies with a total of 664 participants were included in this review. Three studied adverse effects of radiotherapy, three studied adverse effects of chemotherapy and two studied menopausal symptoms associated with breast cancer treatment. Two studies with low risk of bias demonstrated benefit: one with 254 participants demonstrated benefits from calendula ointment in the prevention of radiotherapy-induced dermatitis, and another with 32 participants demonstrated benefits from Traumeel S (a complex homeopathic medicine) over placebo as a mouthwash for chemotherapy-induced stomatitis. These trials need replicating. Two other studies reported positive results, although the risk of bias was unclear, and four further studies reported negative results. The homeopathic medicines used in all eight studies did not seem to cause any serious adverse effects or interact with conventional treatment. No cancer treatments were modified or stopped because of the homeopathic interventions.
We searched the databases until October 2014. We included seven randomized controlled trials, with a total of 1624 participants, comparing dexmedetomidine versus traditional sedatives. All the studies required participants to have an anticipated need for sedation of more than 24 hours. The alternative sedatives included propofol, midazolam and lorazepam. We found no eligible studies in children or for clonidine. Of the seven studies, six were funded by the drug manufacturer, and one did not state any conflict of interest. Compared with traditional sedatives, dexmedetomidine reduced the breathing support time by approximately one-fifth, and the length of stay time in ICU by one-seventh. Dexmedetomidine was at least as effective as traditional sedatives for producing sedation and maintaining a light sedation level. There was no clear evidence in support of dexmedetomidine reducing the risk of delirium (a kind of acute confusion state), as results were consistent with both no effect and appreciable benefit. We had insufficient information to draw conclusions about reducing the risk of coma. Dexmedetomidine doubled the incidence of slow heartbeat, which was the most commonly reported adverse event. Our review provides no evidence that dexmedetomidine changed the overall death rate. The general quality of evidence ranged from very low to low, as most of the studies were at high risk of bias, serious inconsistency and imprecision, or strongly suspected publication bias.
Oral betamimetics for maintenance therapy after threatened preterm labour do not prevent preterm labour. This conclusion is based on 13 randomised controlled trials with a total of 1551 women. In this review, the betamimetics ritodrine and terbutaline did not reduce the rate of preterm birth (eight trials), or prevent problems with babies that required admission to the neonatal intensive care unit (two trials), when compared with placebo, no treatment or other tocolytic drugs. Betamimetics may cause pregnant women to have an increased heart rate (palpitations) and rate of breathing, low blood pressure, nausea and vomiting, and high blood sugar concentrations as side effects.
The evidence is current to May 2016. In this review, we included 13 studies with 514 participants. Seven trials were conducted with community participants, four with in-patients, and two with mixed community and in-patient samples. Participants received various types of memory retraining techniques, including training using computer programs and training in the use of memory aids, such as diaries or calendars. In three studies treatment was provided in groups and in 10 studies treatment was provided individually. Treatment lasted between two weeks and 10 weeks. In these studies, those who received the treatment were compared with a control group. The control group included those who did not receive cognitive rehabilitation or received another form of treatment. The control groups varied. Some studies had a control group wherein people received their usual care, whereas in others individuals in the control groups were placed on a waiting list to receive cognitive rehabilitation. We found that people who received cognitive rehabilitation reported fewer memory problems in daily life immediately after treatment compared with the control groups. This represents a small to moderate effect of the intervention in comparison to the control group. However, there was no evidence that the benefits persisted in the long term. We found no evidence that cognitive rehabilitation improved people's independence in activities of daily living, mood, or quality of life. There was no information about any harm caused to participants from taking part in cognitive rehabilitation. The quality of the evidence ranged from very low (effect on outcomes that relate to everyday activities) to moderate (effect on self-reported memory problems, memory tests, and mood measures). There were a number of flaws in these studies, such as having very few people in them, and these could have affected our findings.
A total of three research studies were identified. Two studies showed that there may be a decrease in CVC-related blood infections if the space in the CVC was washed and filled at regular intervals with urokinase (a drug which dissolves blood clots) with/without heparin (a drug which prevents the formation of blood clots) compared to heparin alone. One study showed that changing the dressing which covered the skin at the insertion of CVC every 15 days rather than every 4 days did not lead to an increased removal of the CVC because they had become infected. No research studies were identified for several other potential strategies which could reduce CVC-related infections in children with cancer.
We found three studies (involving 2270 women), all from high-income countries, that were suitable for this review. The studies looked at the effectiveness of decision support tools designed to be used either independently by women or mediated through the involvement of someone not associated with their care support. No studies looked at shared decision support tools that were intended to help with shared decision making with the pregnant women and their health professionals during pregnancy care visits. We found that the use of these decision support tools made no difference to the type of birth women planned, how women actually gave birth, or in the number of women and babies who experienced harm, although only one study reported harms. There was also no difference in the proportion of women who were unsure about what they wanted. Overall, nearly 65% of women who wanted a VBAC achieved it, while almost all women wanting a caesarean birth had one (97%). We found no difference in the proportion of women who achieved their preferred mode of birth. However, women who used decisional support interventions had less uncertainty about their decision than those that did not use them. Research is needed on the effectiveness of decision support interventions designed to be shared between women and the health professionals caring for them in pregnancy after a caesarean birth.
We identified 21 trials involving 4174 adult, male and female participants with presumed acute ischaemic stroke. The evidence is current to February 2014. Many trials followed participants for at least three to six months. Interventions included isovolaemic regimens (replacing a portion of blood volume with fluid) and hypervolaemic regimens (increasing the total volume of blood by adding fluid) using different types of solutions. This review showed that, when all the studies are taken together, there is no clear evidence of benefit from haemodilution. There is also no clear evidence that any particular mode of haemodilution, with or without blood-letting, using various types of haemodiluting agents, etc, is beneficial. There were no significant serious side effects of this treatment. It is concluded that there is no clear scientific support for the use of haemodilution in the routine treatment of people with acute ischaemic stroke. The overall quality of the evidence was moderate as individual trials were of varying quality. There was little variation among trials.
Different strategies are used to try and prevent this condition, and the review of trials found that some of these are effective. Two interventions, cryotherapy (ice chips) and keratinocyte growth factor (palifermin®) showed some benefit in preventing mucositis. Sucralfate is effective in reducing the severity of mucositis, and a further seven interventions, aloe vera, amifostine, intravenous glutamine, granulocyte-colony stimulating factor (G-CSF), honey, laser and antibiotic lozenges containing polymixin/tobramycin/amphotericin (PTA) showed weaker evidence of benefit. These were evaluated in patients with different types of cancer, undergoing different types of cancer treatment. Benefits may be restricted to the disease and treatment combinations evaluated.
The review authors searched the medical literature for clinical trials that compared pimozide to other drugs, or a dummy drug (placebo), for treating tics in patients with Tourette Syndrome. The trials identified showed that pimozide was more effective at reducing tics than placebo. It was slightly less effective than the drug haloperidol, but showed fewer side effects. There were no important differences between pimozide and risperidone for either reduction of tics or side effects. In future, if trials could be run for longer, it would help the investigation of the nature of side effects caused by these drugs.
This review examined clinical trials on psychological treatments and antidepressant drugs in depressed patients with diabetes. The objective was to determine the effects of these treatments on depression, blood sugar, adherence to diabetic treatment regimens, diabetes complications, death from any cause, healthcare costs and health-related quality of life. Nineteen trials with 1592 participants were identified as relevant for the review. Eight trials with 1122 participants investigated psychological treatments versus usual care (duration of therapy three weeks to 12 months, follow-up after treatment zero to six months). Eight trials with 377 participants examined antidepressant drugs versus placebo (duration of intervention three weeks to six months, no follow-up after treatment). Three trials with 93 participants compared the effects of two different antidepressant medications (duration of intervention 12 weeks, no follow-up after treatment). In summary, psychological treatments and antidepressant drugs have a moderate, yet positive, effect on depression outcomes in diabetes patients. Antidepressant drugs have a positive effect on blood glucose, whereas effects on blood glucose are inconclusive for psychological treatments. Patient-rated quality of life did not benefit from psychological or antidepressant drug treatments. Healthcare costs, death from any cause and diabetes complications have not been examined sufficiently. Serious or severe adverse effects were either rare (pharmacological treatments) or not reported (psychological treatments). Overall, the evidence is sparse and inconclusive due to several low-quality trials and the large variety regarding trial characteristics.
We found four randomised controlled trials, with a total of 924 women, that compared metabolomic profile assessment with morphology assessment of embryos. The women were an average age of 33 years old. All studies were conducted between 2011 and 2013; length of follow-up was not specified in any of them. The evidence is current to 26 Feburary 2018. One study was supported by an unconditional grant from a biotechnology company (Molecular Biometrics Inc.). The very low conditional superiority for the primary outcome and premature termination of the trial were potentially associated with the funder's interest in the results. One study received funding from a national health organisation, but the equipment was provided by Molecular Biometrics Inc., one was self-funded, while the source of funding was not stated in the fourth study. We found low-quality evidence of no meaningful difference between the intervention and control groups in rates of live birth, ongoing pregnancy, miscarriage, or clinical pregnancy, and multiple pregnancy. We found very low-quality evidence of no meaningful difference between the groups for ectopic pregnancy, and low-quality evidence that cancellation rates were higher in the intervention group. Our findings suggest that if the rate of live birth or ongoing pregnancy was 36% in the non-metabolomic group, it would be between 32% and 45% with the use of metabolomics. Data were lacking on other adverse effects. No properly designed studies reported metabolomic assessment of oocyte quality or endometrium receptivity. The overall quality of evidence ranged from low to very low. Limitations included serious risk of bias (associated with poor reporting of methods, attrition bias, selective reporting and other bias), imprecision, and inconsistency across trials.
We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments), looking at the effects of systematic risk assessment in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes), as these are already known to health services and are being treated. The evidence is current to January 2015. Nine trials met our inclusion criteria. Limited data suggest that screening has no effect on deaths (from any cause) or the number of people having a stroke or developing coronary heart disease. Data were also limited for cardiovascular risk factors (blood lipids and blood pressure) where there were some favourable effects with systematic risk assessment, but there were differences between studies and so results are not certain. The evidence was generally of low or very low quality. Included studies were at some risk of bias, with four studies judged at high risk of bias. Bearing this in mind, the results of this review need to be interpreted cautiously. There is currently limited evidence on the effects of systematic risk assessment for the prevention of CVD. We identified five ongoing trials and when the results are available we will incorporate these.
We identified 15 studies involving 17,674 mothers and babies (search date 25 January 2016). We included women at low risk of complications as well as women at increased risk, but not currently experiencing problems. All the trials involved professionally-qualified midwives and no trial included models of care that offered home birth. We used reliable methods to assess the quality of the evidence and looked at seven key outcomes: preterm birth (birth before 37 weeks of pregnancy); the risk of losing the baby in pregnancy or in the first month after birth; spontaneous vaginal birth (when labour was not induced and birth not assisted by forceps; caesarean birth; instrumental vaginal birth (births using forceps or ventouse); whether the perineum remained intact, and use of regional analgesia (such as epidural). The main benefits were that women who received midwife-led continuity of care were less likely to have an epidural. In addition, fewer women had episiotomies or instrumental births. Women’s chances of a spontaneous vaginal birth were also increased and there was no difference in the number of caesarean births. Women were less likely to experience preterm birth, and they were also at a lower risk of losing their babies. In addition, women were more likely to be cared for in labour by midwives they already knew. The review identified no adverse effects compared with other models. The trials contributed enough high quality evidence for each key outcome to give us reliable results for each one. We can be reasonably confident that future trials would find similar results for these outcomes. Most women should be offered ‘midwife-led continuity of care’. It provides benefits for women and babies and we have identified no adverse effects. However, we cannot assume the same applies to women with existing serious pregnancy or health complications, because these women were not included in the evidence assessed.
We searched, in a wide-ranging way, for all the useful studies (randomised controlled trials, or RCTs) we could find on long-term treatment of people with bipolar disorder using valproate or any other mood stabiliser, or antipsychotic drugs, or placebo. Three of us looked at RCTs to make sure they were fair experiments. We extracted data from the studies, put all of the evidence together and carried out a statistical analysis to look for significant results. We conducted these searches to 11 January 2013 and found six studies, including a total of 876 participants. The quality of the studies in terms of design was not good, which means that the effects of some drugs might have been overestimated. All of the trials taken together suggest that valproate might help to prevent relapse in bipolar disorder, especially depressive episodes. However, because of limited available evidence, conclusions on valproate compared with placebo and lithium (or other active drugs) cannot be made with any reliable degree of confidence. Lithium is an important drug to compare with valproate because lithium is already known to be effective in preventing relapses of bipolar disorder. When we combined the findings of all studies comparing valproate with lithium, the evidence did not favour valproate or lithium in terms of efficacy. People taking valproate over a long time were more likely than patients given lithium to keep taking their allocated medication. Clinicians and patients should consider the side effects of valproate, including alopecia, tremor and weight gain. We also found a study that compared valproate taken alone with valproate combination therapy (two drugs taken at the same time). This study compared people who took lithium only or valproate only with people who took valproate and lithium together. No evidence showed that use of valproate and lithium compared with lithium alone helped to ensure that patients kept taking their allocated medication.
Forty-five studies, randomising 1863 participants were included in this review. Thirty two studies presented data that could be included in the meta-analyses.This review showed that regular exercise training significantly improved physical fitness, physical functioning (e.g. walking capacity), and health-related quality of life in adults with chronic kidney disease (CKD). Beneficial effects were also seen on other outcome measures, such as blood pressure, but where the level of evidence is somewhat lower due to too few research studies and or small study populations. Beneficial effects were present in both adults with CKD but not yet in need of dialysis treatment, patients with dialysis (haemodialysis and peritoneal dialysis) and kidney transplant recipients. This systematic review and meta-analysis presents evidence-based data to clinicians and patients on which type of exercise regimen (type of exercises, intensity, frequency and duration of exercise) that should be used to optimise the effect size. The results should be implemented by clinicians who should encourage and inform adults with CKD that there is scientific evidence for beneficial effects of regular exercise training, and who should use an adequate exercise intervention in order to achieve the patient’s and the clinician's goal with the regular exercise.
Four studies including 262 adult participants with Crohn's disease in remission were included. One study (33 participants) compared an elemental diet to a non-elemental (polymeric) diet. One study (51 participants) compared an elemental diet to a normal diet (no supplements). One study (95 participants) compared an elemental diet to 6-mercaptopurine or a no treatment control group. One study (83 participants) compared a non-elemental polymeric diet to mesalamine. The researchers searched the medical literature extensively up to 27 July 2018. The study comparing an elemental diet to a polymeric diet found no difference in remission rates at 12 months. Six elemental diet participants were not able to tolerate the enteral nutritional formula because of taste or smell and were withdrawn from the study. Participants who received half of their total daily calorie requirements as elemental diet and the remaining half by normal diet had a lower chance of relapse at 12 months compared to participants who received a free diet. No side effects were reported in this study. The study comparing an elemental diet to 6-mercaptopurine did not show any difference in relapse rates at 12 months. There was no difference in side effect rates. The only side effect reported in the elemental diet group was surgery due to worsening Crohn's disease. Side effects in the 6-mercaptopurine group included liver injury in two participants, hair loss in one participant and surgery to treat an abscess in one participant. The study comparing a polymeric diet to mesalamine found no difference in relapse rates at six months. Two participants the polymeric diet group experienced nausea and four had diarrhoea. It is unclear if any participants in the mesalamine group had side effects. No serious side effects were reported in any of the studies. The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the effectiveness and safety of enteral nutrition for maintenance of remission in Crohn's disease can be drawn. More research is needed to determine the effectiveness and safety of using enteral nutrition as maintenance therapy in Crohn's disease. Currently, there are four ongoing studies (estimated enrolment of 280 participants). This review will be updated when the results of these studies are available.
We updated our searches of research databases in May 2019. We found 81 studies that tested various ways of trying to help people who had recently quit smoking not to relapse. Five of them were new for this update. Fifty studies included people who had already quit, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on people who needed to stop smoking for a limited period of time because they were pregnant (19 studies), in hospital (six studies), or because of military service (three studies). Most of the studies used behavioural support treatments that tried to teach people skills to cope with the urge to smoke, or followed up with additional leaflets or calls, internet or mobile phone resources, or additional counselling. Some studies tested extending the use of medicines for helping people to quit smoking, in the hope of preventing relapse. The evidence we found does not support the use of behavioural treatments to help prevent relapse after quitting smoking. This result was the same in all of the different groups of people studied. The most promising treatments involved extending treatment with stop-smoking medicine, in particular, varenicline. Extending treatment with bupropion did not appear to help and there was not enough evidence on extending treatment with nicotine replacement therapy. For behavioural treatments, the certainty of the evidence was moderate. This is because of the diversity of results among studies. The certainty of evidence for treatments with quit-smoking medicines varied. There was moderate-certainty evidence for varenicline, moderate-certainty evidence for bupropion, and low-certainty evidence for nicotine replacement therapy (NRT), and for NRT and bupropion together. Certainty in the evidence was limited by small study sizes.
We included two randomised trials with 341 eyes of 238 participants comparing laser treatment to no intervention. There were 121 males and 117 females with an age range from 13 to 67 years. The trials employed different types of laser treatment. One trial employed scatter laser treatment in which lasers were applied to the retina near the new blood vessels using argon laser. Another employed feeder vessel laser coagulation in which lasers were applied directly to feeding blood vessels using xenon arc as well as argon laser. Participants were followed up for an average of 21 to 47 months. There is mixed evidence on the benefits of using laser therapy in people with retinopathy related to sickle cell disease. For instance, the effect of laser therapy on stopping the progression of new blood vessels and the development of new lesions did not differ greatly between the groups. However, there is evidence that laser therapy may prevent loss of vision and sight-threatening complications. Patient-important outcome data, such as quality of life, were not reported. The safety of laser treatment is acceptable, particularly scatter laser treatment using an argon laser. Although xenon arc lasers are associated with a higher number of complications, a loss of vision is not common. However, given that there are few trials with relatively low quality evidence, results should be treated with caution. Further research is needed to examine the safety of laser treatment compared to other interventions. In addition, patient-important outcomes (such as quality of life and loss of driving licence) as well as cost-effectiveness should be addressed. Both trials were at risk of bias due to the way participants were selected for groups (especially since treatment may be required for both eyes). One study was considered to be at risk of reporting bias as some results were only presented for one of the two treatment groups.
In this review we evaluated the efficacy and safety of prophylactic phototherapy in preventing jaundice in preterm or LBW infants. A total of nine clinical trials representing 3449 infants were included. The findings suggest that phototherapy initiated soon after birth (within 36 hours) for preterm or low birth weight infants may prevent the serum bilirubin from reaching a level that would require exchange transfusion and may reduce the risk of impairment of brain and central nervous system development. However, further well-designed studies are needed to evaluate the effects of prophylactic phototherapy on brain and central nervous system development and other long-term outcomes.
Major surgery is usually associated with significant pain. The mainstay of treatment for pain following major surgery is opioid medications (strong pain killers such as morphine). However, opioids are not always entirely effective and are associated with side effects including sleepiness (sedation), shallow breathing (respiratory depression), feeling sick (nausea), and being sick (vomiting). Co-administered medications, like paracetamol, may help improve postoperative pain control and reduce the need for opioids. We included nine clinical trials with a total of 666 participants. We searched several databases to March 2014, to find placebo-controlled, randomized trials (clinical studies where people are randomly put into one of two or more treatment groups, one of which includes a pretend (placebo) group) of nicotine for postoperative pain. We also contacted study authors for additional data. Not all studies reported all of the symptoms (outcomes) listed above, so what we can say about some outcomes is limited. We re-ran the search on 28 April 2015. We will assess the one study of interest when we update this review. Our results indicated that there is low quality evidence that nicotine use results in slightly lower postoperative pain scores 24 hours after surgery. At one hour and 12 hours postoperatively the effect was less certain. Nicotine appeared not to reduce use of opioids at 60 minutes or 24 hours, neither was there evidence that it reduced sedation or vomiting. Nicotine was associated with higher risk of nausea than placebo, and this may limit its use. There was not enough data to evaluate the effects of nicotine use on other side effects associated with opioids, including respiratory depression, or the effects of nicotine use on length of hospital stay following surgery. We downgraded the quality of the evidence to low or very low quality largely because of problems with the way that the studies were designed, which could have exaggerated the results, because there was insufficient data in many of the analyses to be certain about the size of the average effect and because the results of some of the studies varied substantially.
This review compares whether a single fraction of radiotherapy is better than multifractions of radiotherapy for alleviating the symptoms associated with tumours that have spread to the bone. Eleven randomised trials were identified in the published literature that compared single versus multifraction radiotherapy for bone metastases. Pooled analysis of these trials suggested that single fraction radiotherapy was as effective as multifraction radiotherapy in controlling bone pain. However, there were more bone fractures in patients treated by single fraction radiotherapy, and they received further treatment sessions more often than those receiving multifraction radiotherapy.
We included trials published up to July 2017. We found ten studies with a total of 4527 participants that looked at the effects of face-to-face information or education for parents. Seven studies were from high-income countries, and three were from low- or middle-income countries. The interventions were a mix of short (under ten minutes) and longer sessions (15 minutes to several hours) that were delivered to new or expectant parents. We analysed data on the effects of face-to-face information or education on seven different outcomes. According to the included studies, face-to-face information or education may have improved children’s vaccination status, probably slightly improved parents’ knowledge or understanding of vaccination, and may slightly have improved parents’ intention to vaccinate. These interventions may have led to little or no difference in parental attitudes or anxiety related to the intervention. Only one study measured the cost of a face-to-face case management strategy. In this study, the cost of fully immunising one additional child was eight times the cost of usual care, but the intervention was complex, and the study was older, and not widely generalisable. No studies measured parents’ satisfaction with the face-to-face intervention. We judged the certainty of the evidence to be moderate for parents' knowledge or understanding, but low for all other outcomes. We downgraded the certainty of the evidence where studies were judged to have problems with bias from different sources (e.g. the way in which participants were assigned to study groups), where there was a lot of variability in results or imprecise estimates, or where we had misgivings about the choice of outcomes measures. This review suggests that immunisation-focused educational messages may be sufficient to improve vaccination coverage and, to a small degree, knowledge, particularly where awareness is identified as a barrier to vaccination.
The review of three trials, involving 233 women, found there has not been enough research done to show the effects of castor oil on ripening the cervix or inducing labour or compare it to other methods of induction. The review found that all women who took castor oil by mouth felt nauseous. More research is needed into the effects of castor oil to induce labour.
In February 2014, we did a computer search for studies comparing the no-scalpel approach to the vas with the scalpel method. We included randomized controlled trials in any language. For the initial review, we also looked at reference lists of articles and book chapters. We found two trials that looked at the no-scalpel approach to the vas. The trials had somewhat different results. The larger trial showed the no-scalpel method led to less bleeding, infection, and pain during and after the procedure. The no-scalpel approach required less time for the operation and had a faster return to sexual activity. The smaller study did not show these differences. However, the study may have been too small and many men dropped out. The two methods did not differ in the numbers of men who became sterile.
Studies using animal models suggest that allopurinol (a drug commonly used for preventing gout) can reduce the level of brain damage following perinatal asphyxia. Three small randomised controlled trials that examined whether giving allopurinol to newborn infants following perinatal asphyxia affected their outcomes were identified. None of these trials provided any evidence of benefit. Larger trials are needed to exclude important effects on survival and disability.
We found one study comparing zonisamide versus placebo, involving a total of 20 randomised participants with essential tremor. The impact of zonisamide on functional abilities, risk of treatment discontinuation, and adverse events is uncertain because the quality of evidence is very low. Adverse events were only reported in participants from the zonisamide group, making it possible that they were aware of which treatment they had been receiving. Quality of life was not assessed in the study included. The single study we found was small and the possibility of study participants becoming aware of the treatment group means that we cannot be certain about the risk-benefit profile of this treatment.
We searched databases in July 2018 and found 21 studies with 2482 participants. Most studies investigated one of three interventions, namely a form of psychological therapy called cognitive-behaviour therapy (CBT), which teaches skills to change thoughts and behaviours. Skills include coping strategies, or biofeedback or relaxation, which teaches people to reduce their tension either by concentrating on relaxing exercises or through a machine that gives feedback about muscle tension or body temperature. The remaining psychological treatments were examined in single studies; they included writing about emotions and eye movement desensitisation, and reprocessing, which uses eye movements to help people accept their pain and other negative experiences. We were interested in outcomes following treatment and at the longest available follow-up. We found no evidence that psychological treatments resulted in less migraine frequency in the four weeks following treatment. However, we could only include four studies in this analysis that were not high quality. Four studies reported the proportion of people whose migraines reduced in frequency by 50% or more, and in those studies, people who received psychological treatment were twice as likely to respond to treatment (i.e. 50% reduction in migraine frequency) as those in the control group. There was no evidence that psychological treatments affected migraine intensity, medication use for migraine, mood or quality of life. Only two studies assessed adverse events, and so we were unable to draw conclusions. We found very few follow-up data, and no evidence to support or refute any long-term effects of psychological treatment. We rated the quality of the evidence using four levels: very low, low, moderate, or high. High-quality evidence means that we are very confident in the results. Very low-quality evidence means that we are very uncertain about the results. We judged the quality of evidence as very low. There is no evidence that psychological treatments affect the frequency of migraine. More responders (i.e. those reporting a 50% reduction) received psychological treatment than control, but this was based on very low-quality evidence and therefore we are uncertain of this result. In terms of adverse events, we were unable to draw conclusions as there was insufficient evidence. There were very few long-term data available, and no indication that psychological interventions had any long-term effects. Overall there was an absence of high-quality evidence for the effect of psychological treatment on migraines and therefore we are uncertain whether there is any difference between psychological therapies and controls. Funding of high-quality studies is needed and additional studies may change the conclusions of this review.
The Cochrane Schizophrenia Group ran an electronic search for clinical trials involving the use of haloperidol for psychosis-induced aggression in July 2011 and April 2015. We found one study with 110 participants, diagnosed with schizophrenia or schizoaffective disorder. Participants had been physically aggressive during recent hospitalisation and involved in at least one other aggressive event. The study randomised participants to receive either haloperidol, clozapine or olanzapine. Most data presented were impossible to use and it is unclear if haloperidol is effective for reducing aggression or improving mental state for people who are aggressive due to psychosis. There were no data regarding side effects. The number of people leaving the study early from each treatment group was similar. The quality of evidence available is low, only one study with a high risk of selective reporting of results provided data. No firm conclusions can be made until further good-quality data are available.
This systematic review of randomised clinical trials assesses whether antibiotic prophylaxis prevents spontaneous bacterial peritonitis and mortality among cirrhotic patients with ascites (excess fluid in the abdominal cavity) and no gastrointestinal bleeding. Nine trials are included in the review. The pooled rates of spontaneous bacterial peritonitis and mortality indicate that antibiotic prophylaxis reduces both. There are very few reports of adverse events. Reviewing these trials, we found poor methodology, evidence suggesting publication bias, and limited follow-up periods. Thus, the recommendation to prescribe prophylactic antibiotics to cirrhotic patients without gastrointestinal bleeding is hampered by quality of the trials that generated the data. Due to potential hazards, both to society as a whole and the patients, as individuals, before antibiotic prophylaxis can be confidently recommended, trials of better design, well reported, and of longer follow-up are required.
One study compared PLD plus carbo given to women every three weeks versus the standard treatment (paclitaxel (PAC)/carbo every three weeks), and the other added PLD to the standard treatment and compared it with standard treatment only (the latter study also included other treatments not relevant to this review). These studies spanned three years and included 820 and 4100 women, respectively. Most women in these studies had advanced cancer and had undergone surgery to remove as much of the cancer as possible. Key findings Women receiving the PLD/carbo treatment and those given the standard treatment survived for a similar period, but PLD/carbo caused more women to experience low blood counts (anaemia and low platelets) that often led to a delay in treatment or the need to stop treatment. However, PLD/carbo caused far fewer women to experience hair loss and neuropathy (nerve damage causing symptoms such as tingling, numbness, pain, loss of sensation and/or coordination), and so it might help women who find these side effects unacceptable or intolerable. We concluded that three-weekly PLD/carbo is a reasonable alternative to standard platinum-based treatment for newly diagnosed EOC, but more research is needed to establish the safest and most effective dosage and dose frequency. Adding PLD to standard treatment (PAC/carbo) every six weeks did not help women with newly diagnosed ovarian cancer survive longer and was associated with worse effects on blood counts that increased the chance of infection; therefore this triple drug treatment cannot be recommended. Quality of the evidence We considered the evidence related to survival of women after they are treated with PLD/carbo or PAC/carbo, and the evidence related to adverse drug effects to be of high quality.
The evidence on which this review is based was up-to-date as of 26 February 2018. We searched scientific databases and found two trials, with 62 participants included in the analysis. Both trials were conducted at dental schools in the USA and evaluated the use of oral antibiotics in the reduction of pain and swelling reported by adults after having the first stage of root canal treatment under local anaesthetic. The antibiotic used in both trials was penicillin VK and all participants also received painkillers. Key results The two studies included in the review reported that there were no clear differences in the pain or swelling reported by participants who received oral antibiotics compared with a placebo (a dummy treatment) when provided alongside the first stage of root canal treatment and painkillers. However, the studies were small and produced poor quality evidence, and therefore we cannot be certain if the results are correct. Neither study examined the effect of antibiotics on their own, without surgical dental treatment. One trial reported side effects among participants: one person who received the placebo medication had diarrhoea and one person who received antibiotics experienced tiredness and reduced energy after their treatment. Quality of evidence We judged the quality of evidence to be very low. There is currently insufficient evidence to be able to determine the effects of antibiotics in these conditions.
We found, through systematic search, only one study where investigators assessed the usefulness of ketamine for management of severe acute asthma in children. While this single study suggested that there is a lack of evidence for usefulness of ketamine in acute exacerbation of asthma in children, more trials are needed regarding the use of ketamine in acute asthma before more specific recommendations can be made.
The review of 16 randomised controlled trials found no evidence that depot versus daily GnRHa injections produce different rates of live birth/ongoing pregnancy, clinical pregnancy or ovarian hyperstimulation syndrome (OHSS). However, substantial differences could not be ruled out. For example, for a woman with a 25% chance of achieving a live birth or ongoing pregnancy using GnRHa depot, the corresponding chance using daily injection would be between 16% and 30%. For a woman with a 25% risk of severe OHSS using GnRHa depot, the corresponding risk using daily injection would be between 4% and 89%. For a woman with a 25% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using a depot injection would be between 19% and 30% . For a woman with a 25 % chance of severe OHSS using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 9 % and 45 % . Depot GnRHa may increase the cost of an IVF cycle, because it lengthens the period to ovulation and requires the use of higher doses of other hormone drugs. The quality of the studies was unclear due to poor reporting, and only four studies reported live births.
This review compared initial ICS doses for asthma . The results showed that commencing with a moderate dose ICS is as effective as commencing with a high dose ICS and then reducing the dose whilst monitoring symptoms. These results also show that initial moderate dose ICS maybe more effective than initial low dose ICS. No extra benefit was gained by doubling or quadrupling the starting ICS dose. People with asthma should start their treatment with low to moderate doses of ICS.
Three studies involving a total of 316 participants were included in this review. Analysis of the results showed that reversion success lies somewhere between 19.4% and 54.3%. We could not calculate the likelihood and severity of side effects (adverse events) as the studies provided insufficient information to perform this analysis. Potential side effects have been reported in other articles on the subject; these have included hypotension (sudden lowering of blood pressure) or syncope (brief loss of consciousness). No side effects were reported in the three studies reviewed here. In the three studies, reversion was achieved on completion of each VM. Overall, the VM appears to be a simple, non-invasive method of stopping abnormal heart rhythm, but its safety and overall effectiveness are difficult to quantify. Further research is required to improve the evidence surrounding this practice.
A total of 22 randomised controlled trials were included in this review. There is insufficient evidence from these trials to be able to identify one particular intervention for endometrial preparation that clearly improves the treatment outcome for women receiving embryo transfers with either frozen embryos or embryos derived from donated oocytes. Better quality studies are needed to more accurately evaluate each treatment.
We reviewed eight trials involving 5762 participants that compared anticoagulants with antiplatelet agents for preventing recurrent stroke and found no benefit of low intensity anticoagulation over aspirin, and an increased risk of bleeding with high intensity anticoagulation.
This review examined how successful the interventions in the suitable studies were in improving dental health in children aged from 4 to 12 years. The latest search of relevant studies was carried out on 18th October 2012. Interventions were programmes that enabled children to. ∙ Making lasting changes to toothbrushing habits.  ∙ Reduce the amount and how often food and drink known to cause tooth decay were consumed. The trials had to include an educational element which taught skills or gave instructions and one or more accepted techniques to change behaviour. Out of 1518 possible studies found only four were sufficiently relevant and of high enough quality to be included in this review. One small study showed that children who received the behavioural intervention developed fewer caries during the study. Three studies showed that there was less dental plaque (better oral hygiene) in the children in the behavioural intervention groups. More research is needed to confirm these findings. The dental health of 4 to 12 year olds is an important issue - reducing the amount of decay in this group would have a positive impact on overall health, particularly for those living in the poorest communities. More high quality research with well designed programmes will help to establish which techniques are most effective at changing child and parent behaviour to encourage good toothbrushing and discourage sugar snacking.
One randomised clinical trial was included comparing four arms: electro-coagulation alone, electro-coagulation + dimethyl sulphoxide, electro-coagulation + allopurinol and control. The treatment was started in the fifth postoperative day and was continued for five years. Three hundred and six patients were included, but only 223 could be included in the analyses. On the basis of one randomised trial, which did not describe its methodology in sufficient detail to assess risk of bias and quality, excluded 27% of patients after randomisation due to various reasons, and is probably not free from selective outcome reporting bias, there is insufficient evidence to conclude that in patients with colonic cancer liver metastases, electro-coagulation alone brings any significant benefit in terms of survival or recurrence compared with the control group. In addition, there is insufficient evidence for the effectiveness of adding allopurinol or dimethyl sulphoxide to electro-coagulation.
At present there is no completed randomised controlled trial that has assessed the effects of male circumcision on acquisition of HIV and other sexually transmitted infections among men who have sex with men (MSM). Results from observational studies suggest that circumcision may be protective among MSM who practice primarily insertive anal sex, but the role of male circumcision overall in the prevention of HIV and other sexually transmitted infections among MSM remains to be determined.
For many interventions it is difficult to draw any real conclusions due to weaknesses of the included studies. However, reducing the number of daily doses appears to be effective in increasing adherence to blood pressure lowering medication and should be tried as a first line strategy although there is little evidence of an effect on blood pressure reduction. Some motivational strategies and complex interventions appear promising but we need more evidence on their effect through carefully designed randomised controlled trials to confirm these findings.
Eight studies, which included 805 women, were identified that compared combined hormonal contraceptives (mostly, the combined contraceptive pill) with either no treatment, placebo or other medical treatments. The studies assessed the effects of interventions on menstrual bleeding, satisfaction, quality of life, adverse events, and haemoglobin levels (protein in red blood cells that carries oxygen throughout the body). The evidence is current to September 2018. Two studies found that a type of COCP, containing estradiol valerate and dienogest, reduced HMB and improved quality of life and haemoglobin levels when compared with placebo, but at the expense of some minor side effects. There was insufficient evidence to compare contraceptives with other treatments, such as nonsteroidal anti-inflammatories or progestogens. Two studies found that the levonorgestrel-releasing intrauterine system (LNG IUS) was more effective than the COCP at reducing menstrual blood loss. Two trials found no evidence of different effects between the oral contraceptive pill or the hormonal vaginal ring. We found no studies that assessed the effects of the combined hormonal patch (transdermal patch). The quality of the evidence that compared the oral contraceptive pill with placebo was moderate, but the evidence for the other comparisons was either low or very low in quality. The LNG IUS is more effective than the COCP at reducing menstrual bleeding but evidence was insufficient for the other treatment comparisons. This means that, although it is likely that combined hormonal contraceptives can reduce HMB, we cannot be absolutely certain how they compare with other medical treatments for reducing HMB (although LNG IUS appears to be more effective).
The review included three studies on non-surgical treatments in 175 women with a bleeding disorder who were experiencing heavy menstrual bleeding. Twostudies compared desmopressin to placebo and one study compared desmopressin to tranexamic acid. The women included in the studies were selected for one treatment or the other randomly. The studies lasted from two to four months. Two studies of the three studies (with a total of 59 women) found no clear evidence of a difference in desmopressin (1-deamino-8-D-arginine vasopressin) in reducing menstrual blood loss when compared to placebo. One of these studies continued with an open non-randomised comparison of a combination of desmopressin with tranexamic acid versus placebo and found a significant reduction in menstrual blood loss. However, the non-randomised design of this comparison is an additional potential source of bias. The third study (116 women), which had more participants than the other two studies combined, found a greater reduction in menstrual blood loss with tranexamic acid use than with desmopressin. We were unable to present any data on quality of life from this study, since no differences in between the two intervention groups were reported. There was no clear evidence of difference in the risk of side effects with desmopressin as compared to tranexamic acid. None of the studies dealt with cost effectiveness. We were not able to adequately assess the studies in relation to how the women were allocated to the treatment groups and we judged the overall quality of the evidence as poor.
Three randomised controlled trials, involving 212 participants, met the inclusion criteria for this review. The evidence available does not demonstrate that FESS, as practised in the included trials, is superior to medical treatment with or without sinus irrigation in patients with chronic rhinosinusitis. There were no major complications in any of the included trials and FESS appears to be a safe procedure. More randomised controlled trials comparing FESS with medical and other treatments, with long-term follow up, are required.
This update, current to December 2014, uses a network of 137 studies of 8333 eyes to compare antiviral medicines and to find out if interferon or debridement would help. Between one and 28 studies were available to compare seven ophthalmic antiviral drugs, an antiviral taken by mouth, interferon, office procedures to remove the eye's infected surface, and other medicines. The first antivirals, idoxuridine and vidarabine, seem better than no treatment in healing HSV dendritic keratitis within two weeks. Topically applied trifluridine, acyclovir, or brivudine are better and safer than idoxuridine, cure about 90% of treated eyes within two weeks, and have no significant differences in effectiveness. The evidence is conflicting whether ganciclovir is as good as or better than acyclovir. Determining the role of antiviral pills is limited by few studies and inconsistent findings. Interferon, a natural part of the immune system that can be given as an eye drop, is active against HSV infection of the cornea. The integrated use of interferon and an antiviral drug might be slightly better than an antiviral drug by itself. Another treatment is to rub off the infected surface of the eye, but using a wiping method followed by an antiviral drug is not consistently better than just an antiviral medication. Comparisons of one ophthalmic antiviral drug to another have a moderate quality of evidence, except for the appraisal comparing ganciclovir and acyclovir where studies are inconsistent. The quality of the evidence is moderate to low when an ophthalmic antiviral drug was compared to combined antiviral and interferon treatments or to combined antiviral treatment and debridement. Evidence is scarce or poor for placebo-controlled comparisons, comparisons of antiviral treatment to interferon or to debridement, and evaluations of antiviral pills. Proper randomisation could not be assured in nearly a quarter of the studies. Patients or examiners could have known which treatment was assigned in at least half of the studies.
This review examines the effectiveness of speech and language therapy interventions for children with primary speech and language delay/disorder.The review concludes that whilst there may be some support for the effectiveness of speech and language therapy for children with expressive phonological and expressive vocabulary difficulties, the evidence concerning the effectiveness of interventions for expressive syntax is mixed, and no evidence is available concerning interventions for children with receptive language difficulties.
We searched for evidence (October 2017) and found three randomised controlled studies (1099 pregnant women) comparing metformin tablets with placebo (dummy) tablets taken by mouth from 10 to 20 weeks of pregnancy until birth. The studies involved women with obesity; we therefore could not assess the effect of metformin in women who are overweight. Women who were given metformin or placebo during pregnancy had a similar risk of a baby being born large-for-gestational age (measured in weeks since last period). Metformin probably makes little or no difference in the risk of women developing gestational diabetes. Metformin may also have little or no difference in the risk of women developing gestational hypertension (high blood pressure) or pre-eclampsia. Women who were given metformin may gain slightly less weight during pregnancy, but are more likely to experience diarrhoea. There were no other important differences identified for other maternal outcomes including, caesarean birth, giving birth before 37 weeks of pregnancy, shoulder dystocia (a birth complication where the baby’s shoulder gets stuck), perineal trauma (damage to the area between the woman’s vagina and the anus), or heavy bleeding after the baby has been born. Babies of women who were given metformin had similar birthweight to babies of women who were given placebo. We did not identify any other important differences for other infant outcomes of interest: hypoglycaemia (low blood sugar); hyperbilirubinaemia (jaundice); Apgar score at five minutes (a measure of newborn well-being); or death of the baby before or after being born. One study reported similar rates of admission to neonatal intensive care between groups. There is insufficient evidence to support the use of metformin for women with obesity in pregnancy for improving outcomes for the mother and her baby. Metform was associated with increased risk of adverse effects, particularly diarrhoea. A small number of studies are included in this review and no study included women categorised as 'overweight', or looked at metformin in combination with another treatment. More research is needed to evaluate the role of metformin in pregnant women with obesity or who are overweight, as a strategy for improving maternal and infant health, either alone or as an additional intervention.
We searched the literature up to September 2015 and identified 18 generally well-designed randomised controlled trials meeting the eligibility criteria. Nine of these studies focused on specific combinations of health conditions (comorbidity studies), for example diabetes and heart disease. The other nine studies included people with a broad range of conditions (multimorbidity studies) although they tended to focus on elderly people. The majority of studies examined interventions that involved changes to the organisation of care delivery although some studies had more patient-focused interventions. All studies had governmental or charitable sources of funding. Overall the results regarding the effectiveness of interventions were mixed. There were no clear positive improvements in clinical outcomes, health service use, medication adherence, patient-related health behaviours, health professional behaviours or costs. There were modest improvements in mental health outcomes from seven studies that targeted people with depression, and in functional outcomes from two studies targeting functional difficulties in participants. Overall the results indicate that it is difficult to improve outcomes for people with multiple conditions. The review suggests that interventions that are designed to target specific risk factors (for example treatment for depression) or interventions that focus on difficulties that people experience with daily functioning (for example, physiotherapy treatment to improve capacity for physical activity) may be more effective. There is a need for further studies on this topic, particularly involving people with multimorbidity in general across the age ranges. All of the included studies were randomised controlled trials. The overall quality of these studies was good though many studies did not fully report on all potential sources of bias. As definitions of multimorbidity vary among studies, the potential to reasonably combine study results and draw overall conclusions is limited. Overall, we judged that the certainty or confidence we can have in the results from this review is moderate but due to small numbers of studies and mixed results we acknowledge the uncertainty remaining and the potential that future studies could change our conclusions.
This review investigated whether having mental health workers on-site to work with physicians at their offices would change the care that physicians provide. Forty-two studies were reviewed in which on-site mental health workers, such as counsellors or psychiatrists, worked alongside physicians to provide therapy to patients. The review found that when there were mental health workers on-site, patients may reduce the number of visits to their doctors; doctors may reduce how often they refer patients to off-site mental health specialists; doctors may reduce the number of drugs they prescribe to the patients who see the mental health workers; and the costs related to those drugs may be lower. However, these reductions were small and not found consistently in all the studies.   The review also found that there may be little or no difference in how the doctors prescribe drugs or refer patients who have mental health problems but are not seeing the on-site mental health workers. It is also not known what the effect of on-site mental health workers had on how well physicians recognised and diagnosed mental health problems.
Study characteristics: Our search (August 2015) identified 21 eligible trial reports (in 18 primary publications). In total, 3089 infants participated. Eight trials (2086 infants) examined the effect of topical ointments or creams. Most participants were very preterm infants cared for in health-care facilities in high-income countries. Eleven trials (1184 infants) assessed the effect of sunflower, sunflower seed, and other vegetable oils. Nine of these trials were undertaken in low- or middle-income countries and all were based in health-care facilities rather than home or community settings. Results: Analyses of these trial data provided low quality evidence and did not show that emollients prevent infection or death in preterm infants. Conclusions: These analyses do not provide evidence that the use of emollient therapy prevents invasive infection or death in preterm infants in high-, middle- or low-income countries. Since these interventions are low cost, readily accessible and generally acceptable, further randomised controlled trials, particularly in both community- and health care facility-based settings in low-income countries, may be justified.
This review includes evidence from three randomised controlled trials with a total of 251 participants. All three trials were at some risk of bias, which means that their results may not be reliable. Two trials compared radial head replacement with ORIF for treating highly fragmented radial head fractures. These trials showed that after radial head replacement, patients had significantly better elbow function and fewer adverse events than those treated with ORIF at between one and three years follow-up. One trial compared biodegradable pins with standard metal screws in treating displaced radial head fractures. It found similar results for the two types of materials in terms of elbow function and adverse events. Overall, there is some evidence to support radial head replacement for treating highly fragmented radial head fractures instead of attempting to fix the fractured bone back in place. However, the evidence is low quality and it is unknown whether these results would apply in the longer term or more generally. Using biodegradable implants may be as good as metallic implants for fixing some usually more stable fractures but more evidence is needed to confirm this.
We searched electronic databases until March 2011 and found 16 randomised controlled trials with a total of 616 participants. We grouped these studies by type of treatment into eight groups: Eight studies were on brain stimulation, of which five used electronic and three magnetic stimulation. Three studies were on exercise programmes, two on acupuncture and one each on self-hypnosis, transcutaneous electrical nerve stimulation (TENS) and a cognitive behavioural programme. The included studies used a range of different methods to measure pain and other outcomes. Comparison groups also varied and included sham interventions, waiting lists and other pain treatments. For any given type of intervention, only a few studies were found, and they included only small numbers of participants. Often the reported detail was insufficient. The overall quality of the studies was low. For instance, several studies used inappropriate comparison groups such as waiting lists. Consequently, the effectiveness of the treatments is uncertain. An additional search in November 2014 identified more recent studies that will be included in an update of this review. For one type of treatment—transcranial direct current stimulation (tDCS)—results from two studies could be combined. The pooled results suggest that tDCS reduced pain in the short term and in the mid term. Also, exercise programmes for chronic shoulder pain provided pain relief. We found no evidence to suggest that repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), acupuncture, self-hypnosis or TENS is better than the respective control interventions for reducing chronic pain. Regarding outcomes other than pain, such as anxiety, depression or quality of life, as well as long-lasting side effects, no overall conclusions were possible, given that data were sparse. The included studies do not permit firm conclusions regarding whether treatments other than medication for chronic SCI pain are effective and safe. Trials with greater numbers of participants and improved study quality are needed to determine the effectiveness and safety of such treatments.
This review investigated the best available evidence for interventions aimed at preventing postnatal psychosis. Unfortunately, no studies were found that could be included. Nevertheless, this review raises many unanswered questions and strongly suggests that future research on postnatal psychosis is much needed. Despite a growing interest in women’s mental health, knowledge and research on postnatal psychosis is still very limited. Future well-designed, well-conducted and well-reported studies are necessary to help improve prevention of symptoms and treatment for women with postnatal psychosis. This plain language summary has been written by a consumer Benjamin Gray; Service User and Service User Expert. Rethink Mental Illness.
Eight studies met the inclusion criteria of this Cochrane review, and seven studies provided information for the review. The non-surgical treatment was chemoradiotherapy only in five studies and radiotherapy only in three studies. We included a total of 1114 participants undergoing non-surgical treatment (510 participants) or surgical treatment (604 participants) in the various analysis in the seven studies that provided information. Methods similar to tossing a coin were used to decide whether a participant received non-surgical treatment or surgical treatment and ensure that the participants in the two groups were similar. Most trials included people who were healthy in aspects other than the condition requiring surgery. The evidence is current up to 4th March 2016. Most information was from trials that compared chemoradiotherapy with surgery. There was no difference in long-term deaths between chemoradiotherapy and surgery in people with oesophageal cancer who are fit for surgery. More people died in radiotherapy than surgery in people with oesophageal cancer who are fit for surgery in the long-term. There was no difference in long-term cancer recurrence between non-surgical treatment and surgery. The difference between non-surgical and surgical treatments were imprecise for short-term deaths, the percentage of participants with serious adverse in three months, and the percentage of participants who had recurrence of cancer in and around the food-pipe. The health-related quality of life (covering aspects such as activity, daily living, health, support of family and friends, and outlook) was higher in non-surgical treatment between four weeks and three months after treatment, although it is unclear what this difference means to the patient. The difference between non-surgical and surgical treatments were imprecise for medium-term health-related quality of life (three months to two years after treatment). Chemoradiotherapy only appears to be at least equivalent to surgery in terms of short-term and long-term survival in people with one type of oesophageal cancer called squamous cell cancer and who are fit for surgery. There is more uncertainty in the comparison of chemoradiotherapy only versus surgery for another type of oesophageal cancer called adenocarcinoma, and we cannot rule out significant benefits or harms of definitive chemoradiotherapy versus surgery in this type of oesophageal cancer. More people had difficulty in swallowing prior to their death after chemoradiotherapy treatment compared to surgical treatment. Radiotherapy only results in less long-term survival than surgery (about 40% increase risk of deaths). Further well-designed studies that measure outcomes that are important for patients are necessary. The quality of evidence was low or very low because the included studies were small and had errors in study design. As a result, there is a lot of uncertainty regarding the results.
Several trials have addressed the effects of anabolic-androgenic steroids for alcoholic liver disease. This systematic review could not demonstrate any significant effects of anabolic-androgenic steroids on mortality, liver-related mortality, liver complications, and histology of patients with alcoholic liver disease. Anabolic-androgenic steroid intervention is not associated with a significant increase in non-serious adverse events, but with the seldom occurrence of serious adverse events. Accordingly, there is no evidence supporting the use of anabolic-androgenic steroids for alcoholic liver disease, but further randomised clinical trials may be needed to settle the question.
We searched for randomised controlled trials testing varenicline, cytisine or dianicline. We found 39 studies of varenicline compared to placebo, bupropion or nicotine patches. We also found four trials of cytisine, one of which compared it to nicotine replacement therapy. We include one trial of dianicline, which is no longer in development, and so not available to use as a quitting aid. To be included, trials had to report quit rates at least six months from the start of treatment. We preferred the strictest available definition of quitting, and results which had been biochemically confirmed by testing blood or bodily fluids.We conducted full searches up to May 2015, although we have also included several key trials published after that date. From the information we found (27 trials, 12,625 people), varenicline at standard dose more than doubled the chances of quitting compared with placebo. Low-dose varenicline (four trials, 1266 people) roughly doubled the chances of quitting, and reduced the number and severity of side effects. The number of people stopping smoking with varenicline was higher than with bupropion (five trials, 5877 people) or with NRT (eight trials, 6264 people). Based on the evidence so far, we can calculate that varenicline delivers one extra successful quitter for every 11 people treated, compared with smokers trying to quit without varenicline. The most common side effect of varenicline is nausea, but this is mostly at mild or moderate levels and usually clears over time. People taking varenicline appear to have about a 25% increased chance of a serious adverse event, although these include many which are unrelated to the treatment. We also note that more people were lost from the control groups than from the varenicline groups by the end of the trials, which may mean that the count of events in the control groups is lower than it should be. After varenicline became available to use, there were concerns that it could be linked with an increase in depressed mood, agitation, or suicidal thinking and behaviour in some smokers. However, the latest evidence does not support a link between varenicline and these disorders, although people with past or current psychiatric illness may be at slightly higher risk. There have also been concerns that varenicline may slightly increase heart and circulatory problems in people already at increased risk of these illnesses. The evidence is currently unclear whether or not they are caused or made worse by varenicline, but we should have clearer answers to these questions when a further study is published later this year. The varenicline studies were generally of high quality, providing evidence that we consider to be reliable and robust. We rate the quality of the evidence comparing varenicline with NRT as moderate quality (we are reasonably confident of the stability of the evidence), since in some of them the participants knew which treatment they were receiving (i.e. non-blinded open-label trials). We judge the evidence from the cytsine trials to be of low quality (we have limited confidence in the evidence), as there are only two trials, with relatively low numbers included.
Some studies have suggested that medicines (such as statins and fibrates) taken to lower blood cholesterol may reduce the risk of melanoma skin cancer. Our review of 16 studies did not find any clear evidence to support such a suggestion, but we cannot exclude a useful effect of such drugs until more studies become available.
Eighty-one trials that evaluated the effects of educational meetings were included in this review. Based on these studies, we concluded that educational meetings alone or combined with other interventions can improve professional practice and the achievement of treatment goals by patients. The effect on professional practice tended to be small but varied between studies, and the effect on patient outcomes was generally less. It is not possible to explain the observed differences in effect with confidence but it appeared that higher attendance at the meetings was associated with greater effects, that mixed interactive and didactic education was more effective than either alone, and that the effects were less for more complex behaviours and less serious outcomes.
We identified 15 studies (1644 elderly women) comparing single dose, short-course (3 to 6 days) and long course (7 to 14 days) antibiotic treatment for uncomplicated symptomatic UTI in elderly women. Our review suggests that single dose treatments are less effective than short or long courses, but better accepted by the patients. On the other hand longer courses may have more side effects. On the basis of the evidence available at present, an antibiotic treatment of 3 to 6 days could be sufficient for treating uncomplicated UTIs in elderly women, although more studies on specific, commonly prescribed antibiotics are needed.
Atrial natriuretic peptide (ANP) has been shown to increase urine production and to reduce kidney inflammation. The aim of this review was to investigate the use of ANP in preventing AKI and treating established AKI. We identified 19 studies (11 prevention and 8 treatment) using low or high dose ANP, enrolling 1,861 patients. There was no difference in the number of deaths between ANP and control for studies preventing or treating AKI. The need for dialysis was significantly lower in both the low dose ANP treatment and prevention studies as well as for patients undergoing major surgery. The length of time spend in hospital and ICU was shorter for patients receiving low dose ANP. High dose ANP was associated with more hypotension and cardiac arrhythmias in patients with established AKI. ANP may be associated with improved outcomes when used in low doses for preventing AKI and in managing postsurgery AKI. There were no significant adverse events in the prevention studies, however in the high dose ANP treatment studies there were significant increases in hypotension and arrhythmias.
We did not find any completed randomised controlled trials that assessed melatonin given to the mother during pregnancy to help protect the baby's brain. One ongoing trial (planning to include 60 women) was identified. This trial is designed to determine what dose of melatonin can reduce brain injury for babies when given to their mothers before very preterm birth (before 28 weeks of pregnancy). Further studies are needed to establish whether melatonin given to the mother in pregnancy can protect the baby's brain against brain injury. The babies in these trials need to be followed up over a long period so that we can monitor the effects of melatonin on childhood development, including impairments or disabilities such as cerebral palsy.
In this review we investigated the use of TwHF as an immunosuppressive therapy for patients with primary NS. We only considered two standardised TwHF extracts which have lower toxicity profiles and fewer adverse effects than other non-standardised preparations. We reviewed the evidence from 10 randomised studies enrolling 630 Chinese patients with primary NS. Of these, four studies (293 patients) reported that when TwHF was used there was a significantly increased number of patients achieving complete, and complete or partial remission without increasing adverse events. There were no significant differences in complete, partial, or complete or partial remission when TwHF was compared with prednisone in four studies (223 patients). There were also no significant differences in complete, partial, or complete or partial remission when TwHF was compared with CPA in two studies (114 patients). One study reported TwHF significantly improved kidney function (decreased serum creatinine) when compared with CPA. TwHF was associated with a lower risk of psychosis than prednisone; and there was less likelihood of hair loss when compared to CPA. The quality of evidence was poor; there were only 10 studies, enrolling a total of 630 patients; follow-up was short; the maximum number of studies included in a comparison was four; and we had major concerns over the quality of the included studies. TwHF may have an add-on effect on remission in patients with primary NS; however there is insufficient evidence to assess if TwHF is as effective as prednisone or CPA.
Our searches found 546 trials, of which five were relevant. In total, 14,252 children were randomly assigned to receive either an intervention targeting autumn asthma attacks or usual care. Four small studies (approximately 200 to 1200 children in each) gave children extra asthma medication; these additional medications were omalizumab, leukotriene receptor antagonist tablets, or increased doses of inhaled steroids. One study sent a medication reminder letter over the summer holidays to parents of children with asthma. One trial gave children either omalizumab or placebo. Omalizumab is an antibody designed to alter the immune response. It was given by injection regularly over four to six weeks before school return (i.e. over the bulk of the summer holidays). The children in this study had known allergic asthma. The study showed that omalizumab might reduce autumn attacks. Eleven per cent of those receiving omalizumab had an asthma attack during the first 90 days compared to 21% of those receiving placebo. Three studies used leukotriene receptor antagonist tablets, either montelukast or pranlukast. Although the results of one study suggested that seasonal montelukast might reduce autumn attacks, there was no evidence of reduced attacks in the other two later trials, including a second larger trial of montelukast. There was no evidence that sending a reminder letter reduces the number of children requiring an unplanned healthcare contact. No study provided evidence that the total number of children experiencing adverse events was greater in the intervention than in the usual care group. Our findings were limited by the small numbers of studies identified and because these studies used different interventions and definitions of asthma exacerbations. Further research is needed to better understand how to prevent seasonal attacks, including interventions suitable for children with mild asthma, where expensive and painful treatments are not justified.
There have been few investigations of client feedback in psychological therapies for children and adolescents with mental health problems. Most of them were carried out in the USA with older children and adolescents (11 to 18 years old). There was no clear evidence supporting the effectiveness of client feedback in psychological therapy for children and adolescents. It cannot be ruled out that client feedback has positive effects on psychotherapy outcomes in children and adolescents. High-quality studies are needed to provide sufficient evidence. Future studies should also include younger children, and should take place in countries other than the USA.
Several drugs are available to treat anaemia for people who have kidney disease but whether these drugs are similar or different in their ability to improve symptoms of anaemia, such as tiredness and breathlessness, and whether they are equally safe based on their risks of causing a stroke or a heart attack, is not clear. This is because research studies that compare the effects of one drug directly with another are not common. We have found 56 studies that measure the safety and how these drugs help to improve how patients who have kidney disease feel, function and survive that have involved 15,596 people. Our last search of the literature was in February 2014. We are somewhat confident that four of the drugs (epoetin alfa, epoetin beta, darbepoetin beta and methoxy polyethylene glycol-epoetin beta) are better than a placebo injection to prevent patients needing to have a blood transfusion. We are less certain that biosimilar drugs are better than placebo to help patients avoid a blood transfusion. All erythropoiesis-stimulating agents cause high blood pressure, but we cannot be very sure if biosimilar products have effects on blood pressure. We cannot be confident in the other important effects of these drugs - we are not sure whether the drugs are similar or different in their effects on the chances of death, a heart attack or stroke; the risk of having a clot in a fistula or vascular catheter needed for dialysis; or the chances of needing dialysis for people who have milder kidney disease. We are unsure whether the different drugs are better at improving symptoms such as tiredness or breathlessness than others as the available research studies generally do not measure these aspects of treatment very well. Overall, whether different drugs are safer or better at treating symptoms of anaemia for people with kidney disease is poorly known. It is likely that most if not all the drugs prevent the need for a patient to require a blood transfusion. The choice of which drug to use to treat anaemia when a patient has kidney disease can be decided between patients and health professionals based on shared preferences for how frequently the drug is given and considering drug costs and availability.
In this updated review there were few randomized controlled trials which evaluated the efficacy and safety of psychostimulants in myotonic dystrophy. One randomized controlled trial of selegiline involving 11 participants did not demonstrate any benefit. Four studies of another drug modafinil suggested inconsistent and slight benefits. Only two of these studies used the gold standard test, a sleepiness scale, to evaluate hypersomnia and found non significant improvement. In these four studies modafinil seemed well tolerated. Further randomized trials are needed to determine the utility of psychostimulants for myotonic dystrophy.
We searched scientific databases for randomised trials (clinical studies that randomly put people into different treatment groups) that systematically provided CVD risk scores or usual care to adults without a history of heart disease or stroke. The evidence is current to March 2016. Funding for the majority of trials came from government sources or pharmaceutical companies. We identified 41 trials that included 194,035 participants. Many of the studies had limitations. Low-quality evidence suggests that providing CVD risk scores had little or no effect on the number of people who develop heart disease or stroke. Providing CVD risk scores may reduce CVD risk factor levels (like cholesterol, blood pressure, and multivariable CVD risk) by a small amount and may increase cholesterol-lowering and blood pressure-lowering medication prescribing in higher risk people. Providing CVD risk scores may reduce harms, but the results were imprecise. There is low-quality evidence to guide the use of CVD risk scores in clinical practice. Studies had multiple limitations and used different methods to provide CVD risk scores. It is likely that further research will influence these results.
We identified 38 studies involving 9445 participants examining several types of interventions for enhancing adherence to dietary advice for preventing and managing many chronic diseases. The main chronic diseases involved were cardiovascular diseases, diabetes, hypertension, and renal diseases. Interventions shown to improve at least one diet adherence outcome are: telephone follow-up, video, contract, feedback, nutritional tools and more complex interventions including multiple interventions. However, these interventions also showed no difference in some diet adherence outcomes compared to a control/usual care group making the results inconclusive about the most effective intervention to enhance dietary advice. Interestingly, all studies including clients with renal diseases reported at least one diet adherence outcome showing a statistically significant difference favouring the intervention group, no matter which intervention was provided. The majority of studies reporting a diet adherence outcome favouring the intervention group compared to the control/usual care group in the short-term also reported no significant effect at later time points. Studies investigating interventions such as a group session, individual session, reminders, restriction and behaviour change techniques reported no diet adherence outcome showing a statistically significant difference favouring the intervention group. Finally, interventions were generally of short duration, studies used different methods for measuring adherence and the quality of the studies was generally low.
We searched for randomised or quasi-randomised controlled trials which compared psychological treatments to each other or to no treatment in sickle cell disease. We included seven studies in the review, of which five, with 260 people, had data we could enter into the review. One study showed that cognitive behaviour therapy reduced the affective part of pain (feelings about pain), but not the sensory part (pain intensity). Another study of this therapy had inconclusive results for coping strategies and showed no difference on how different groups used the health service. A study using cognitive behavioural therapy with teenagers and their families at home did not show any difference when compared with education about sickle cell disease. One education study did not show a reduction in depression. Furthermore, one study in patient education helped improve attitudes to healthcare workers and medication use in adolescents and young adults. The authors believe that some patient education seems relevant for children, adolescents and young adults, while methods to improve the ability to cope in both children and adults are important. Nonetheless, these results may not apply to across all ages, clinical severity, types of pain (acute or chronic) that people with sickle cell disease have, or which country they live in. More research needs to be done in this area.
We found 18 randomised controlled trials, all comparing different timing methods in one treatment cycle for IUI, with a total of 2279 couples. The evidence was current to October 2013. We found no evidence of a difference in live birth rates between timing methods. We also found no evidence of a difference between any of the groups in rates of pregnancy or adverse events (multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS)). Most of the evidence was of low or very low quality. The main limitations were poor reporting of study methods, imprecision and losses to follow up. More research is needed.
We identified two randomised studies evaluating two different drugs in two different types of patients. One of these drugs, an angiotensin-converting enzyme (ACE) inhibitor (enalapril), had a short-term beneficial effect on heart function in survivors of childhood cancer with asymptomatic cardiac problems caused by anthracyclines compared with placebo. However, the drug had no significant beneficial effect on other important outcomes and was associated with side effects such as dizziness and fatigue. This study was of reasonable/good quality. The other study was of low quality and found no effect of a short treatment with phosphocreatine in childhood leukaemia patients with symptomatic or asymptomatic cardiac problems compared with a control treatment with vitamin C, adenosine triphosphate, vitamin E, and oral coenzyme Q10. We could make no definitive conclusions about treatment options for anthracycline-induced cardiac problems in childhood cancer patients and survivors. High-quality studies are needed to determine if there are drugs that improve heart function in these patients.
We conducted a systematic search of the literature on preventing occupational injuries among construction workers. We included 17 studies in this updated review, rating the evidence as very low quality. Multifaceted interventions and company incentives for upgrading equipment may be effective in reducing injury. However, an evidence base is still needed for the vast majority of safety measures that safety manuals, consultants and safety courses routinely recommend. What was studied in the review? We looked at different types of workplace interventions, including the introduction of new regulations, safety campaigns, training, inspections, occupational health services, and company subsidies. We evaluated the quality of the studies and the effectiveness of interventions, rating the evidence as very low quality. What are the main results of the review? Introducing regulations alone may or may not be effective for preventing non-fatal and fatal injuries in construction workers. Regionally oriented interventions such as a safety campaigns, training, inspections or occupational health services may not be effective for reducing non-fatal injuries in construction workers. However, a multifaceted safety campaign and a multifaceted drug-free workplace programme at the company level, along with subsidies for replacement of scaffoldings, may be effective in reducing non-fatal injuries. Additional strategies are needed to increase the employers' and workers' adherence to the safety measures that are prescribed by regulation. How up-to-date is this review? We searched for studies that had been published up to 1 April 2017.
We found two small studies demonstrating an improvement of muscle strength with pinacidil and acetazolamide. There was only one trial considering treatment of paralytic attacks, demonstrating a decrease in the severity and frequency of the attacks using diclorophenamide. We did not find other randomised or quasi-randomised studies, but only case reports and anecdotal articles using other drugs to reduce paralyses attacks. Further research is needed to determine the best treatment for reducing the frequency and severity of attacks and to treat or prevent permanent muscle weakness.
A total of 28 randomised controlled trials were included, with a total of 1273 menopausal women. Over 95% of the study populations were postmenopausal women. Women's ages ranged from 36 to 80 years. Treatment duration varied from one week to one year. In more than 80% of the trials DHEA was administered orally with the daily doses varying between 10 mg and 1600 mg. We found no evidence that DHEA improves quality of life. There was some evidence that it was associated with androgenic side effects (for example acne, unwanted hair growth (hirsutism)). It was uncertain whether DHEA decreased menopausal symptoms, but DHEA may have slightly improved sexual function. The quality of the evidence was moderate for both quality of life and side effects. We downgraded the quality of evidence based on the lack of data on randomisation, allocation, or blinding; small study sizes overall; and limited data available.
We included 41 randomised controlled studies (clinical studies where people are randomly put into one of two or more treatment groups) with a total of 10,681 people in our review. There were five different interventions which we call 'supportive interventions': changes to the organisation of nutritional care (13 studies, 3456 people), changes to the feeding environment (5 studies, 351 people), modification of the meal profile or pattern (12 studies, 649 people), additional supplementation of meals (10 studies, 6022 people) and home meal delivery systems (1 study, 203 people). Monitoring participants over time (follow-up) ranged from ‘duration of hospital stay’ to 12 months. The comparator groups received 'usual' care. More than half of all participants took part in studies investigating the additional supplementation of meals (for example a protein-energy oral nutritional supplement in addition to the usual diet). It is possible that supportive interventions for enhancing dietary intake in nutritionally vulnerable groups reduce death from any cause (approximately 23 fewer cases of death per 1000 participants in favour of supportive interventions). However, this has to be confirmed by more evidence from high-quality randomised controlled studies. The number of participants experiencing any medical complication did not differ substantially between the supportive interventions and the comparator groups. The same was found for health-related quality of life (which is physical, mental, emotional and social health attributed to health), patient satisfaction, nutritional or energy intake and days spent in hospital. Economic costs were not well investigated. Only three studies reported on side effects, describing intolerance to the nutritional supplement (such as diarrhoea or vomiting in 5 of 34 participants) and discontinuation of oral nutritional supplements because of refusal or dislike of taste (567 of 2017 participants). After analysing 15 studies in 1945 participants we found a beneficial effect of supportive interventions compared with comparators on weight: on average people in the supportive interventions groups increased their weight 0.6 kg more than people in the comparator groups. This evidence is up to date as of September 2016. The overall quality of evidence ranged between moderate to very low, mainly because for most of our outcomes there was only a small number of studies and participants to achieve reliable information, or because risk of bias made results uncertain. However, if some randomised controlled studies with low risk of bias for our patient-important outcomes and a good number of participants were performed, this review could quickly provide good guidance for better health care.
However, the review of trials found that drinking clear fluids up to a few hours before surgery did not increase the risk of regurgitation during or after surgery. Indeed there is an added benefit of a more comfortable preoperative experience in terms of thirst and hunger. Some children are considered more likely to regurgitate under anaesthetic, including those who are obese or have stomach disorders. More research is needed to determine whether these children can also safely drink up to a few hours before surgery.
We found 14 studies with a total of 747 participants (260 adults; 487 children). The volume of saline used in the studies varied: five studies used 'very low' volumes (nasal sprays providing less than 5 mL saline per nostril per application), two studies used low-volume (between 5 and 59 mL saline per nostril per application introduced with a syringe) and four studies used high-volume solutions (more than 60 mL per nostril per application). Eight studies used hypertonic saline, five used isotonic saline and three studies did not provide this information. Two studies used two different types of saline solutions. Seven studies did not say how they were funded. The other seven were funded either by the investigators' department or research grants from regional or national government. No studies were funded by pharmaceutical companies. Nasal saline irrigation compared with no saline irrigation Nasal saline irrigation may have benefits in both adults and children in relieving the symptoms of allergic rhinitis compared to no saline irrigation and it is unlikely to be associated with adverse effects. It is not possible to tell from this review whether there is a difference between the different volumes and concentrations of saline solution. Adding nasal saline irrigation onto 'pharmacological' allergic rhinitis treatment It is uncertain whether adding nasal saline irrigation to pharmacological treatment (intranasal steroids or oral antihistamines) helps to improve the symptoms of allergic rhinitis compared to using pharmacological treatments alone. The use of nasal saline irrigation is unlikely to be associated with adverse effects. Nasal saline irrigation compared to 'pharmacological' allergic rhinitis treatment There is not enough evidence to know whether nasal saline irrigation is better, worse or the same as using intranasal steroids. No studies reporting the outcomes we were interested in compared nasal saline irrigation with oral antihistamines. The overall quality of evidence for nasal saline irrigation compared with no saline treatment was eitherlow quality (our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect) or very low quality (we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect). This was because the studies were mostly very small and used different methods to measure the same outcome. Since saline irrigation could provide a cheap, safe and acceptable alternative to intranasal steroids and antihistamines further high-quality studies are needed.
In this review prevention with antioxidant supplements of oesophageal, gastric, small intestinal, colorectal, pancreatic, liver, and biliary tract cancers is assessed. The review includes 20 randomised clinical trials. In total, 211,818 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo. Trial quality was exceptionally good. Based on properly designed and conducted randomised clinical trials, convincing evidence that beta-carotene, vitamin A, vitamin C, and vitamin E or their combinations may prevent gastrointestinal cancers is not found. A total of 2057 of 95084 participants (2.2%) randomised to antioxidant supplements and 1548 of 78935 participants (2.0%) randomised to placebo developed gastrointestinal cancers. These antioxidant supplements even seem to increase mortality. A total of 17114 of 122,501 participants (14.0%) randomised to antioxidant supplements and 8799 of 78693 participants (11.2%) randomised to placebo died. Selenium alone may have preventive effects on gastrointestinal cancers. This finding, however, is based on trials with flaws in their design and needs confirmation in properly conducted randomised clinical trials.
We included 11 randomised controlled trials conducted in the United States, Europe, Asia and Africa in this review. In total, 687 eyes of 679 participants underwent routine trabeculectomy for glaucoma control. Some participants were at a higher risk of failure than others, for example if they had had previous glaucoma surgery, were of African origin, or if they had secondary glaucoma. Five studies enrolled participants at low risk of trabeculectomy failure, five studies enrolled participants at high risk of failure, and one study enrolled people with both high and low risk of failure. None of the included trials enrolled participants with combined trabeculectomy/cataract surgery. Our review showed that the risk of failure of trabeculectomy at one year after surgery was slightly less in those participants treated with MMC compared to 5-FU. All of the included randomised controlled trials contributed to this result, with a mixed study population of high- and low-risk participants and varied methodology of antimetabolite application. We did not detect any significant differences between the subgroups of participants at low and high risk of failure, but the power of this analysis was low. We identified no difference between the visual outcomes of the group that received MMC and the group that received 5-FU at one year postoperatively nor in the number of drops used postoperatively. However, we found evidence to suggest that MMC was more effective at lowering intraocular pressure than 5-FU in both high- and low-risk participants, achieving a lower mean intraocular pressure postoperatively than in those who were treated with 5-FU at one year. This effect seemed to be greater in the high-risk populations. Evaluating the overall complications across all studies revealed a slight favour toward using MMC, particularly with the incidence of epitheliopathy and hyphaema. There was a trend towards bleb leaks, wound leaks, late hypotony and cataract formation in the MMC-treated group. None of the studies reported quality of life. We graded the quality of the evidence as low, mostly due to the risk of bias in the included studies. One bias we commonly encountered came from the different techniques of antimetabolite administration, making it difficult to conceal which medicine was being used. Furthermore, most studies only had a few complications to report, which meant that there were low numbers overall to include in the analysis of complications.
In one of the only randomised trials of antipsychotic medications for treating amphetamine psychosis, Leelahanaj (2005) reported that olanzapine and haloperidol delivered at clinically relevant doses both showed similar efficacy in resolving psychotic symptoms (93% and 79%, respectively), with olanzapine showing significantly greater safety and tolerability than haloperidol as measured by frequency and severity of extrapyramidal symptoms. These outcomes are consistent with treatments for schizophrenia indicating equivalent efficacy between atypical anti-psychotics and conventional anti-psychotics, mostly haloperidol with older drugs causing more severe side effects (Leucht 1999).While anti-psychotic medications demonstrate efficacy in providing short-term relief when a heavy user of amphetamines experiences psychosis, there is no evidence to guide decisions regarding long-term clinical care using these medications for preventing relapse to psychosis.
We searched for evidence on 15 May 2017. We did not find any trials for inclusion in this review. We excluded five trials because they were not randomised controlled trials. There is no evidence available to guide how best to investigate the causes of stillbirth. Seeking to determine the causes of a baby's death is an essential component of quality maternity care in any setting. Future trials on this topic would be helpful, but such trials would need to be designed in a way that ensures all parents in the trial still receive the minimum standard of care in their local setting. Future trials would need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should be considered in any future trials.
The review authors searched the medical literature and found two small randomised controlled trials (98 infants) measuring/investigating the benefit of either infusion of base or of a fluid injection (bolus) in the treatment of preterm infants with metabolic acidosis. Infants were given an infusion of sodium bicarbonate on the first day of postnatal life, compared with no treatment or a fluid bolus with albumin. There was no clear evidence that the base infusion corrected metabolic acidosis more effectively. One of the studies (62 newborns) reported no difference in early deaths at one week or in the incidence of bleeding in the brain. Neither study assessed longer-term neurological disabilities.
We included seven randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) in our review. These involved 500 adults undergoing eye surgery under local anaesthesia. We looked at any additional effect of adding hyaluronidase to local anaesthetic on the pain experienced during eye surgery. We also looked at participant and surgical satisfaction scores and if any harms were reported after using hyaluronidase in the injection solution. None of the studies reported on costs. Of the seven included trials, we pooled the results of four trials (289 participants) as the results were reported in a similar manner. They found that addition of hyaluronidase did not significantly reduce pain during surgery. Among the three remaining trials (211 participants) lack of data reporting in two trials made it difficult to pool the results. The overall result of looking at all these trials together suggests there was no significant reduction of pain with using hyaluronidase in eye nerve blocks. We found moderate quality evidence from two trials (122 participants) to suggest that addition of hyaluronidase increased participant satisfaction scores. Three studies involving 141 participants looked at surgical satisfaction, which was reported as superior with hyaluronidase in the two larger studies and not significantly different in one small study (19 participants). None of the included studies reported any harmful effects of hyaluronidase. The included trials that reported on pain during surgery were at low risk for bias. The overall quality of evidence was low because of variations in the effect on pain reduction. We contacted all trial authors to request more information on the trials, but the data were not available. Moderate quality studies reported greater participant and surgical satisfaction with hyaluronidase. Analgesia alone does not take into account the full spectrum of the beneficial effects of hyaluronidase. Patient comfort with the eye surgery is also likely to be improved by a speedy onset and reduced eye movements due to hyaluronidase.
This review, which included searches of databases from January 1990 through March 31, 2014, found 58 community coalition-driven studies, which addressed a wide array of health outcomes and risk behaviors. Only studies of community coalitions with at least one racial or ethnic minority group representing the target population and at least two community-based public or private organizations were included. This review examined the effects of four types of strategies or interventions used by community coalitions. Community system-level change strategies (such as initiatives targeting physical environments like housing, green spaces, neighborhood safety, or regulatory processes and policies) have produced small inconsistent effects; broad health and social care system-level strategies (such as programs targeting behavior of staff in a health or social care system, accessibility of services, or policies, procedures, and technologies designed to improve quality of care) have had consistently positive small effects; interventions that used lay community health outreach workers or group-based health education led by professional staff have produced fairly consistent positive effects; and group-based health education led by peers has had inconsistent effects. This review shows that interventions led by community coalitions may connect health and human service providers with ethnic and racial minority communities in ways that benefit individual health outcomes and behaviors, as well as care delivery systems. However, to achieve the same levels of health across communities, regardless of race or ethnicity, we need to know specifically how a program does or does not work. This will require better information on how some programs described in this review brought about beneficial change and theresources needed, so they can be replicated. Furthermore, we need better scientific tools to improve our ability to identify effects of programs on whole community systems and to understand the leverage points that, when employed appropriately, shift the distribution of health toward equity.
We included 15 studies. The studies covered 3520 people. Although most studies were small with fewer than 120 participants, there were two larger studies with 2012 and 671 participants included. There was a great variation in many of the important elements among the studies, including the type of anaesthetics used and the levels of nitrous oxide used. No study was designed to measure accidental awareness, but rather they measured it as a secondary outcome. Although there were 3520 participants included in the studies, there were only three reports of a participant becoming aware. These were reported in two studies, and one was thought to be due to an error in the anaesthetic procedure. Nine studies reported where the funds for the research were obtained. Two were funded by pharmaceutical companies, suggesting a potential bias, whereas five were funded through Universities or Government health research grants or a charity, limiting the risk of bias. The remaining two studies reported that there was no conflict of interest, also reducing the risk of bias in these studies. Due to safety issues, all of the anaesthetists had to know what anaesthesia was being used. However, this means that the study results may have been biased. Other indicators suggested a low risk of bias, or an unclear risk because of missing information. The quality of the evidence is also low due to the lack of reports of a participant becoming aware. It is not possible to draw any conclusions from this review. The included studies were mainly too small, and only two studies reported any events. The review question is inadequately supported by the lack of strong evidence. The effect of nitrous oxide is hardly observed due to the small sample size.
This review found that cervical preparation decreased the length of time necessary for an abortion procedure, but did not seem to decrease rates of uncommon abortion complications. The medication called misoprostol worked better with less side-effects than other similar medications. Misoprostol is most effective with the least side-effects when placed in the vagina, but when placed under the tongue it is equally effective. Another drug called mifepristone worked better than misoprostol; however, it is more expensive to use. All methods of preparation take at least 2-3 hours or more to work. The review could not determine whether women preferred one method best.
Results from recent clinical trials showed that surgery reduced the risk of death. However, survivors were left with moderate to severe disability requiring help in their daily life activities. These results only apply to people 60 years of age or younger.
We systematically searched various medical databases to determine whether veno-venous bypass is required routinely during liver transplantation. We identified a total of three randomised clinical trials with high risk of systematic error and high risk of random errors which compared veno-venous bypass (n = 65) with no veno-venous bypass (n = 66). None of the trials reported patient or graft survival. There were no differences regarding kidney failure or blood transfusion requirements between the two groups. None of the trials reported on the complications related to veno-venous bypass or the requirement of veno-venous bypass in the control group. We also identified one trial with high risk of systematic error and high risk of random errors which compared needle technique (percutaneous approach) (n = 20) with open technique (n =19) of veno-venous bypass. The patient or graft survival was not reported in this trial. There was no difference in veno-venous bypass related complications between the two groups. The operating time was shorter in the percutaneous technique group. There is currently no evidence to support the routine use of veno-venous bypass in liver transplantation.
There were nine studies with 1520 participants. There was moderate quality evidence that post-treatment exercises can reduce both the rate and the number of recurrences of back pain. However, the results of exercise treatment studies were conflicting. Adverse (side) effects of exercising were not mentioned in any of the studies. Limitations of this review include the difference in exercises across studies, thus making it difficult to specify the content of such a programme to prevent back pain recurrences.
This review found some evidence from five randomized controlled trials, involving a total of 687 patients that suggested local infusion of a drug into the affected artery is more effective than infusion into a vein, and is also associated with a lower risk of unwanted bleeding. No particular drug was more effective in preventing limb loss or death than another. The drugs investigated were streptokinase, urokinase, recombinant tissue plasminogen activator and pro-urokinase. More research is needed to confirm these findings. All of the findings of this review came from small studies that involved people with peripheral arterial ischaemia of differing severity.
This review asks whether the risk of developing asthma, which is a disease caused by many factors, can be decreased by reducing single allergen levels in children with genetic susceptibility, or whether the reduction of more than one type of allergen exposure simultaneously will lead to a better outcome. As a direct comparison could not be made using current research we made indirect comparisons using trials that had compared single or multiple interventions with a control. In children who are at risk of developing childhood asthma 'multifaceted' interventions, which involve both dietary allergen reduction and environmental change to reduce exposure to inhaled allergens, reduce the odds of a doctor diagnosing asthma later in childhood by half. However, the effect of these multifaceted interventions on wheeze reported by parents was inconsistent and there was no beneficial effect on night-time coughing or breathlessness. Single ('monofaceted') interventions were not significantly more effective than controls in the reduction of all outcomes, but there remains uncertainty as to whether multiple interventions are more effective than single component interventions.
The review of 15 trials found that it was better than no treatment or minimal treatment, but not as effective as psychological therapies like cognitive-behaviour therapy. Relaxation techniques have potential as a simple first-line psychological treatment for depression. Those who do not respond within a set time could be offered more complex psychological treatment such as cognitive-behaviour therapy.
We performed a thorough literature search to identify studies published up to 15 May 2016. We identified 16 studies reporting information on 1146 people with pancreatic or periampullary cancers which were considered to be eligible for potentially curative surgery based on CT scan staging. These studies evaluated diagnostic laparoscopy and compared results of the procedure with the eventual diagnosis by the surgeon that the cancer was not resectable during major abdominal operation or examination under microscope. All of the studies were of unclear or low methodological quality in one or more aspects, which may undermine the validity of our findings. Of those people with what CT suggests seems to be a potentially surgically curable cancer, the percentage in whom more extensive cancer was found on further staging with diagnostic laparoscopy or laparotomy ranged between 17% and 82% across studies. The median percentage of people in whom cancer spread was not detected by CT scan was 41%. Adding staging laparoscopy to CT scan might decrease the number of people with unremovable disease undergoing unnecessary major operations to 20% compared to those who undergo unnecessary major operation after CT scan alone (41%). This means that using diagnostic laparoscopy could halve the rate of unnecessary major open operations in people undergoing major surgery for potentially surgically curable pancreatic cancer.
This review of randomised controlled trials included 30 studies involving more than 6000 participants. Most of the trials were poorly reported and had flaws in their methods that could have affected their results. Few trials tested the same comparison. Most of the results for the 25 separate comparisons, frequently tested within one trial only, failed to show that one implant was better than the other under comparison. There was a consistent finding of one serious complication (avascular necrosis) with the sliding hip screw in comparison with five different types of cancellous screws. However, this was not reflected in a decrease in re-operations for this group. Additionally, the sliding hip screw was found to take longer to insert and to have an increased operative blood loss compared with multiple screws or pins. This review found no evidence from trials undertaken so far that there were any major differences between different implants in patient survival or complications related to the operation.
In this review, we examined if involvement of an indigenous healthcare worker (IHW) (when compared to absence of an IHW) in asthma education programs improves asthma related outcomes in Indigenous children and adults with asthma. There was only one study involving 113 people eligible for inclusion in this review. The participants showed improvement in the patient's asthma knowledge score, the parent's asthma skill score and a reduction in the number of days missed from school in children who were cared for by an indigenous healthcare worker. However as exacerbation frequency was not reduced and there was only a single, small study, we cannot be confident of the results although we think it is likely that the involvement of IHW is beneficial. Nevertheless, given the complexity of health outcomes and culture as well as the importance of self-determination for indigenous peoples, the practice of including IHW in asthma education programs for indigenous children and adults with asthma is justified, but should be subject to further randomised controlled trials
We searched for randomised controlled trials that compared early movement with delayed movement of the elbow after elbow fracture. We included one trial reporting results at times ranging from two to 47 months for 81 people who had had an elbow fracture that involved the head of the radius. The evidence from this trial is of very low quality. The trial found no important differences between early and delayed mobilisation in the numbers of participants with pain or limitations in their range of elbow motion. All participants were reported as being able to use their arms for full activities of daily living and none had changed their occupation or lifestyle. There was no mention of fracture complications. We concluded that there was a lack of reliable evidence to answer the question of whether early mobilisation improved function without increasing complications in adults with elbow fractures.
We identified 27 trials with a total of 10,187 participants in searches conducted up to November 2013. Most data come from trials testing one drug (recombinant tissue Plasminogen Activator, rt-PA) given into a vein up to six hours after acute ischaemic stroke, but several other drugs were also tested and at different times to treatment after stroke and given into an artery in the brain rather than into a vein in the arm. All trials compared a clot-dissolving drug with a placebo (control) group. Most trials included participants with moderate to severe stroke. All trials took place in hospitals that were used to treating people with stroke. Differences between trials mean that not all trials contribute information to all outcomes, but we have used all available data. Most trials included participants after a computed tomography (CT) brain scan had excluded a brain haemorrhage as the cause of symptoms (a few trials used magnetic resonance brain scanning instead). There is general agreement between the earlier trials and the one recent trial added in this update (IST-3) for all main outcomes, and between the 12 trials that tested rt-PA and the 15 trials that tested other clot-dissolving drugs. The main difference between IST-3 and earlier trials was that IST-3 had many participants above 80 years. Clot-dissolving treatment can reduce the risk of long-term dependency on others for daily activities, in spite of there being an increased risk of bleeding in the brain which also increased the risk of early death. Once the early bleeding risk had passed, at three or six months after stroke, people given clot-dissolving drugs were more likely to have recovered from their stroke and to be independent, especially if they had been treated within the first three hours after stroke. Older people benefited as much as younger people. Giving aspirin at the same time as clot-busting drugs increased the risk of bleeding and should be avoided. Further analyses of individual patient data factors such as findings on brain scanning before treatment, and of different ways of giving the treatment, may give more information than the summary data that we used here. Meantime, people who think that they are experiencing a stroke should get to hospital quickly, be assessed by a stroke doctor, have a brain scan and receive clot-dissolving treatment as fast as possible. They should not hesitate by thinking that they will be 'too old' for treatment. The treatment is very effective if started within three hours of stroke and definitely improves outcome if given up to 4.5 hours after stroke, but later than that the effects are less clear and are still being tested in trials. More information is needed from trials in people with mild stroke to see if the benefit of clot-dissolving drugs outweighs the risk of haemorrhage. The evidence comes mostly from well-conducted randomised trials run by stroke experts. Some trials (8/27) were run by companies that make the clot-dissolving drugs, but most trials (19/27, including most participants) were funded by Government or charity sources independently of drug companies. These results apply to a wide range of people with a wide range of severities of stroke and other medical conditions.
We included 47 trials with 3581 participants of 18 TCHMs in this review. All were conducted in mainland China between 1997 and 2013 with participant numbers ranging from 26 to 240 and an average study duration of 12 weeks. There were significant problems with the methods in many of the trials, particularly with how participants were allocated to treatments, how outcomes were measured and how thoroughly harmful effects were monitored. For these and other reasons, we rated the overall quality of the evidence as variable, ranging from moderate to very low. This means that we are uncertain, and often very uncertain, about the accuracy of the results. Despite these reservations, we found seven TCHMs which each had potentially large benefits in studies comparing TCHMs to no treatment or Western Medicine. Three of these – Nao XinTong, NaoMaiTai and TongXinLuo – had the strongest evidence to justify further research. We found that the risk of harmful effects was at least 5% higher than the risk for participants in the control group for NaoMaiTai and TongXinLuo, but the quality of this evidence was poor. We think further research of some TCHMs for vascular dementia is justified, but it is important that the quality of trial conduct and reporting be improved by adhering to published best-practice standards.
Seven studies with 837 participants, aged from one to 63 years old were included in this review update. This review was limited by few studies and the quality of evidence was very low to low. In adults, we found that culture-specific programmes did not improve any of our primary outcomes, but were better in improving quality of life (although the mean difference was less that the minimum important difference for the score) (secondary outcome). In children however, when data were combined from studies, culture-specific programmes reduced severe exacerbations requiring hospitalisation (primary outcome), while single studies showed improved asthma control, asthma knowledge and adherence outcomes for our secondary outcomes. The available evidence showed that culture-specific education programmes for adults and children from minority groups are likely effective in improving asthma-related outcomes. Although more robust evidence is required, asthma education programmes should be as culturally specific as possible in the context of chronic disease management and the complexity of health outcomes and culture, In the absence of any economic data, cost-effectiveness studies are also required The quality of the evidence was very low to low for all outcomes.
This review aimed to determine the efficacy of early interventions, including psychological, social and pharmacological interventions to prevent relapse or recurrence of depressive disorders in children and adolescents.The review included nine studies that assessed the efficacy of antidepressant medication and psychological therapies in reducing the risk of a future depressive episode in children and adolescents. Trials varied in their quality and methodological design, limiting conclusions that could be drawn from the result. Overall, the review found that antidepressant medication reduces the chance that children and adolescents will experience another episode of depression, compared with a pill placebo. Psychological therapies also look promising as a treatment to prevent future depressive episodes, however given the aforementioned issues concerning trial quality and design, along with the small number of trials included in the review, it is unclear how effective these therapies are at present.
We searched multiple databases to find studies that examined pharmaceutical chelating agents as treatment for ASD symptoms. We found only one randomised controlled trial that evaluated oral dimercaptosuccinic acid (DMSA) for ASD, but this trial did not use ideal methods for answering our question. The evidence is current to November 2014. The trial that we found was conducted in two phases. During the first phase, 77 children with ASD were assigned randomly to receive seven days of glutathione lotion or placebo lotion, followed by three days of oral DMSA. Forty-nine children who excreted high levels of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off, with the cycle repeated up to six times. Results from the included study show that multiple rounds of oral DMSA did not have an effect on any of the ASD symptoms measured in children found to be high excreters who had already received three doses of a pharmaceutical chelating agent. Currently no clinical trial evidence suggests that pharmaceutical chelation is an effective intervention for ASD. Given prior reports of serious adverse events, such as changes to calcium levels in blood, kidney impairment and reported death, risks of using pharmaceutical chelating agents for ASD currently outweigh proven benefits. The quality of the evidence is poor, with only one study, which had methodological shortcomings, included in this review. These factors, when combined, preclude confidence in the findings. However, before further trials are conducted, more evidence is needed to show that heavy metals cause or worsen the severity of autism, and the safety of pharmaceutical chelating agents for participants must be established.
We identified two trials up to the 19th September 2016. Both of them evaluated the use of tranexamic acid, one for haemoptysis caused by tuberculosis and the other for haemoptysis from a variety of causes. Tranexamic acid significantly reduced the bleeding time, but it did not make any difference to the number of patients who were still suffering from haemoptysis when it was evaluated at seven days after the start of treatment. Severe adverse effects were not reported and mild side effects were not different between patients receiving tranexamic acid and those not receiving tranexamic acid. There is too little evidence to judge whether any antifibrinolytics should be used to treat haemoptysis.
After searching Cochrane Schizophrenia's database in March 2018 and assessing the search results, we included one randomised controlled trial (clinical studies where people are randomly put into one of two or more treatment groups) from the Netherlands (70 participants) and one from Iran (60 participants). Both trials used aspirin as an add-on treatment to standard antipsychotic medication and compared it with placebo (a dummy treatment), also as an add-on to standard treatment. Participants receiving aspirin had slightly better results for their mental state, which was measured with the Positive and Negative Symptom Scale (PANSS). For side effects related to stomach problems, there seemed to be no clear difference between the groups. The same applied to changes in hospital status and leaving the study early. However, all these results were based on analyses of very poor data and graded as very low-quality evidence. No trial gave usable information on cognitive functioning or quality of life. This review was based on results from only two small trials, which made it impossible to say whether aspirin would be a good treatment option for people with schizophrenia. More information from the trials that are underway could strengthen the results of this analysis.
We included six trials involving 510 patients for this review. The number of patients included in the trials varied from 40 to 202. All trials had a high risk of bias, that is, the trials may overestimate benefits and underestimate harms. There was no significant difference in risk of death between the two groups. The rate of serious complications was higher in the patients who underwent biliary drainage prior to operation compared with those who underwent surgery directly. The quality of life was not reported in any trial. There was no significant difference in the length of hospital stay between the two groups. The costs were not reported in any of the trials. Based on the currently available best evidence, there is no justification for the use of routine drainage of bile before a major operation in patients with obstruction to the flow of bile. Routine biliary drainage should not be funded and may result in litigations. Furthermore, well designed trials with low risk of systematic errors and low risk of random errors (low risk of play of chance) may be necessary.
Therefore, we looked at all the research in children with central lines who received, or not, LMWH and only found one study with a total of 186 participants. This study did not have enough participants to show if this medication protects children with central lines from getting blood clots. The study also did not show that children on LMWH, at the doses given, experience too much bleeding because of its use. The included study did not report any additional adverse events. There were two deaths within the study in the standard care arm, and neither were due to a blood clot. Future studies looking at the role of this medication (LMWH) and if it protects children with central venous lines from getting blood clots are needed.
This review is based on a search for trials carried out in July 2012, and includes 10 studies with 686 participants. The aim was to determine the effects of trifluoperazine for schizophrenia when compared with placebo (a ‘dummy’ treatment). As expected, people given trifluoperazine showed a significant improvement compared to placebo in both the short and medium term, reinforcing the use of this well-established typical antipsychotic for people with schizophrenia. However, trifluoperazine can cause side effects such as confusion, agitation, having a dry mouth and blurred vision, but causes less sedation and dizzy spells, so is generally well tolerated by people with schizophrenia. The authors of the review conclude that trifluoperazine has similar effectiveness to other common antipsychotic drugs, although it may cause more side effects. Evidence used in the review was also graded as low or very low quality. In the light of this, use of other antipsychotic drugs should be considered before starting on trifluoperazine. Most of the included studies were conducted roughly 40 years ago so new, large, comprehensive and independent research trials are needed. This plain language summary has been written by a consumer Ben Gray from RETHINK.
We conducted the literature search up until 26 November 2016. We identified 8 studies involving a total of 263 participants with PD. All trials aimed to improve either gait or balance function. Most of the studies compared VR with physiotherapy. VR interventions may lead to greater improvements in step and stride length compared with physiotherapy interventions. We found limited evidence that improvements in gait, balance, and quality of life were similar to those found in active control interventions. No adverse events were reported. Fewer studies compared VR with passive control interventions, and evidence was insufficient to determine how VR compares with no active intervention. At present, only a few studies have been done, making generalisation of the findings difficult. Further study is needed to confirm and expand the evidence base for VR in PD. In general, the quality of the evidence was low or very low. This was the result of small sample sizes and a large amount of heterogeneity between trials with regard to study design and outcome measures used.
This Cochrane review examined which antibiotics are best for treating late onset neonatal sepsis, in terms of effectiveness and side effects. The authors searched the medical literature and found only one study that met all the criteria the authors were looking for. This study, from 1988, enrolled 28 newborn infants. Some of the newborns received a beta lactam antibiotic by itself while others got the beta lactam plus another antibiotic, an aminoglycoside. There were no significant differences between the two kinds of antibiotic treatment in this study. The Cochrane review authors concluded that there is not enough research to recommend one kind of antibiotic treatment over another for late onset neonatal sepsis.
This summary of an updated Cochrane review presents what we know from research about the benefits and harms of manual therapy and exercise in people with frozen shoulder. After searching for all relevant studies published up to May 2013, we included 32 trials (1836 participants). Among the included participants, 54% were women, average age was 55 years and average duration of the condition was six months. The average duration of manual therapy and exercise interventions was four weeks. —manual therapy and exercise compared with glucocorticoid (a steroid that reduces inflammation) injection into the shoulder Pain (higher scores mean worse pain) People who had manual therapy and exercise for six weeks did not improve as much as people who had glucocorticoid injection—improvement in pain was 26 points less (ranging from 15 to 37 points less) at seven weeks (26% absolute less improvement). • People who had manual therapy and exercise rated their change in pain score as 32 points on a scale of 0 to 100 points. • People who had glucocorticoid injection rated their change in pain score as 58 points on a scale of 0 to 100 points. Function (lower scores mean better function) People who had manual therapy and exercise for six weeks did not improve as much as people who had glucocorticoid injection—improvement in function was 25 points less (ranging from 15 to 35 points less) at seven weeks (25% absolute less improvement). • People who had manual therapy and exercise rated their change in function as 14 points on a scale of 0 to 100 points. • People who had glucocorticoid injection rated their change in function as 39 points on a scale of 0 to 100 points. Treatment success 31 fewer people out of 100 rated their treatment as successful with manual therapy and exercise for six weeks compared with glucocorticoid injection—31% absolute less improvement (ranging from 13% to 48% less improvement). • 46 out of 100 people reported treatment success with manual therapy and exercise. • 77 out of 100 people reported treatment success with glucocorticoid injection. Side effects Out of 100 people, three had minor side effects such as temporary pain after treatment with manual therapy and exercise for six weeks compared with glucocorticoid injection. • 56 out of 100 people reported side effects with manual therapy and exercise. • 53 out of 100 people reported side effects with glucocorticoid injection. Evidence of moderate quality shows that the combination of manual therapy and exercise probably improves pain and function less than glucocorticoid injection up to seven weeks, and probably does not result in more adverse events. Further research may change the estimate. Low-quality evidence suggests that (1) the combination of manual therapy, exercise and electrotherapy (such as therapeutic ultrasound) may not improve pain or function more than glucocorticoid injection or placebo injection into the shoulder, (2) the combination of manual therapy, exercise, electrotherapy and glucocorticoid injection may not improve pain or function more than glucocorticoid injection alone and (3) the combination of manual therapy, exercise, electrotherapy and oral non-steroidal anti-inflammatory drug (NSAID) may not improve function more than oral NSAID alone. Further research is likely to change the estimate. High-quality evidence shows that following arthrographic joint distension, the combination of manual therapy and exercise does not improve pain or function more than sham ultrasound, but may provide greater patient-reported treatment success and active range of motion. Further research is very unlikely to change our confidence in the estimate of effect. No trial compared the combination of manual therapy and exercise versus placebo or no intervention.
We included data from two trials, which included 87 participants. The trials compared surgical with non-surgical treatment for these fractures in the thoracolumbar region of the spine. Both trials had limitations in their methods that could reduce the reliability of their results. They reported contrasting results for patient pain and function at a minimum of two years after treatment. One study found patients had less pain and better function after surgery compared with patients who did not have surgery. The other trial found the opposite. Both trials found there were more early complications in the surgical group and only participants of this group had subsequent additional surgery. This involved the removal of the implant either to resolve a complication or routinely. One trial reported that surgery was over four times more costly than non-surgical treatment. Our review concluded that the weak evidence from these two trials was insufficient to say whether surgery or non-surgical treatment was better for these fractures. However, surgery is likely to be associated with more early complications and the need for subsequent surgery, as well as greater initial healthcare costs.
Offering personally tailored activities to people with dementia living in care homes may slightly improve challenging behaviour when compared with usual care, although we did not find evidence that it was any better than offering activities which were not personally tailored. In one study, staff members reported that people in the group receiving personally tailored activities had a slightly worse quality of life than the control group. Personally tailored activities may have little or no effect on the negative emotions expressed by the participants. Because the quality of some of the evidence was very low, we could not draw any conclusions about effects on the participants' positive emotions, mood, engagement (being involved in what is happening around them) or quality of sleep. Only two studies mentioned looking for harmful effects; none were reported. None of the studies measured effects on the amount of medication participants were given, or effects on carers. We concluded that offering activity sessions to people with moderate or severe dementia living in care homes may help to manage challenging behaviour. However, we did not find any evidence to support the idea that activities were more effective if they were tailored to people's individual interests. More research of better quality is needed before we can be certain about the effects of personally tailored activities.
We identified 27 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups), involving 3048 opioid-dependent participants. For 21 studies the average age of participants was in the range 25 to 40 years − in one study the average age was 47 years, while in two studies involving adolescents, the average age of participants was in the range 17 to 20 years (3 studies did not report the average age of participants). In four studies, all or nearly all participants were male, while in three studies less than half the participants were male. In most studies males comprised between one half and three-quarters of participants, a balance that is typical of the population of people who are opioid dependent. Fourteen of the studies took place in the USA, while the remaining studies were in eight other countries. The studies compared buprenorphine with methadone (6 studies), clonidine or lofexidine (14 studies), or different rates of buprenorphine dose reduction (7 studies). Fourteen studies reported funding from sources other than industry; in seven studies funding or medications were provided by a pharmaceutical company. The funding source was unclear for seven studies. Compared to clonidine or lofexidine, people receiving buprenorphine for opioid withdrawal will have less severe signs and symptoms, be likely to stay in treatment longer, experience fewer side effects, and be more likely to complete the scheduled period of treatment. The effectiveness of buprenorphine is probably similar to tapered doses of methadone, but we are uncertain whether withdrawal symptoms resolve more quickly with buprenorphine. We are also uncertain whether rapid reduction in the dose of buprenorphine is more effective than slow reduction and whether this depends on the context of withdrawal. We assessed the quality of the evidence to be very low to moderate for the comparison of buprenorphine versus clonidine or lofexidine, low to moderate for the comparison of buprenorphine versus methadone, and very low to low for the comparison of different rates of dose reduction. Further evidence could change the findings, particularly for buprenorphine compared to methadone and for different rates of reduction of buprenorphine dose.
This review, which is an update of one published in 2002, includes nine studies that involved 946 teenagers, almost all males. The studies were conducted in different parts of the USA and involved young people of different races whose average age ranged from 15 to 17 years. Results indicate that not only do these programs fail to deter crime, but they actually lead to more offending behavior. The intervention increases the odds of offending by between 1.6 to 1 and 1.7 to 1. Government officials permitting this program need to adopt rigorous evaluation efforts to ensure that they are not causing more harm to the very citizens they pledge to protect.
This review looks at whether having an advance statement leads to less hospitalisation (either voluntary or involuntary), less contact with mental health services and whether there is an improvement in general functioning. Two studies were found, involving 321 people. Both took place in England. One trial involved the person concerned making a joint crisis plan in collaboration with the psychiatrist, care coordinator and project worker (high intensity), while the other required filling in a booklet called ‘preferences for care’ (low intensity). Both studies were compared to the usual care in the area concerned. Since the interventions were quite different, and not all outcomes were measured by both studies, it is quite difficult to compare the trials. Those who filled in the booklet showed no decrease in admission to hospital (voluntary or involuntary) or contact with out-patient services, when compared to usual care. The high intensity group showed no differences in voluntary admissions compared to those in usual care, but were less likely to be hospitalised involuntarily, or assessed under the Mental Health Act. They were also less likely to be violent. There was no difference in use of psychiatric out-patient services by those in the intervention groups. These are small studies and more research is needed, but it is suggested that using an advance treatment directive could be an alternative to community treatment orders.   (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org)
During pregnancy, a woman's blood pressure falls in the first few weeks then rises again slowly from around the middle of pregnancy, reaching pre-pregnancy levels at term. Pregnant women with very high blood pressure (systolic over 160 mmHg, diastolic 110 mmHg or more) are at risk of developing pre-eclampsia with associated kidney failure and premature delivery, or of having a stroke. The review of 35 randomised controlled trials including 3573 women (in the mid to late stages of pregnancy, where stated) found that while antihypertensive drugs are effective in lowering blood pressure, there is not enough evidence to show which drug is the most effective. Fifteen different comparisons of antihypertensive treatments were included in these 35 trials, which meant that some comparisons were made by single trials. Only one trial had a large number of participants. This trial compared nimodipine with magnesium sulphate and showed that high blood pressure persisted in 47% and 65% of women, respectively. Calcium channel blockers were associated with less persistent hypertension than with hydralazine and possibly less side-effects compared to labetalol. There is some evidence that diazoxide may result in a woman's blood pressure falling too quickly, and that ketanserin may not be as effective as hydralazine. Further research into the effects of antihypertensive drugs during pregnancy is needed.
Only two trials (60 participants, three months treatment) could be included. Both studies suggested that metformin plus insulin treatment lowered HbA1c somewhat more than placebo plus insulin. Improvement in insulin sensitivity, body weight or serum lipids were not seen in either study. However, one study showed a small decrease in insulin dosage by 10%. Side effects were mainly gastrointestinal upset in both studies and hypoglycaemia (low blood sugar) in one study. There was no information on health-related quality of life, costs, morbidity or mortality in either study.
The evidence on which this review is based is up to date as of 22 July 2013. The only study included was based in rural areas of the city of Trivandrum in Kerala, India. The study included 191,873 apparently healthy adults aged 35 years or older living in 13 clusters with an average of 14,759 participants in each cluster. Screening took place in seven clusters (96,517 participants) and six clusters acted as a control (95,356 participants). Participants were excluded if they were bedridden, if they had open tuberculosis, other debilitating diseases or were already suffering from oral cancer. Healthcare workers trained in the detection of oral lesions undertook the screening of participants and the social history of participants including use of paan, tobacco, alcohol and dietary supplements was recorded. The review found that overall there is not enough evidence to decide whether screening by visual inspection reduces the death rate for oral cancer and there is no evidence for other screening methods. However, there is some evidence that it might help reduce death rates in patients who use tobacco and alcohol although the only included study may be affected by bias. The evidence presented is of low quality and limited to one study assessed as at high risk of bias.
In June 2016 we searched for randomised controlled trials (RCTs) involving the use of drains after leg artery surgery. We identified three eligible trials involving 333 wounds in 222 patients, mainly aged over 65, who had leg artery surgery. Both men and women were included and all of the wounds were in the groin area as part of bypass and endarterectomy operations to improve blood flow. The studies involved small numbers of patients and were not clearly described. All three studies had serious weaknesses in the way they were designed and performed. The results of the individual studies do not provide reliable information because of weaknesses in study design. It is unclear whether wound drains are beneficial or harmful because we did not find any useful information. None of the studies gave information on whether drains shortened or lengthened the number of days that patients had to spend in hospital. None of the studies gave information about how drains affect patients' quality of life. Overall, we found that the quality of the evidence about the effects of drains after leg artery surgery was very low and we were not able to tell whether drains lead to benefits or harms for patients. Better quality research is needed if patients and healthcare providers think that this is an important topic. This plain language summary is up to date as of 8 June 2016.
We included 11 studies with a total of 674 participants. The participants in the studies were aged from 8 to 79. The studies were conducted in a number of countries (six from Pakistan, two from the USA, one from Taiwan and two from South Africa). All but one of the 11 studies reported the difference in recurrence rate between needle aspiration and incision and drainage. Four studies compared symptom scores associated with the procedure and two studies compared time to resumption of normal diet. Three studies reported adverse effects/events associated with the intervention. Two studies reported complications of the disease process itself. The evidence is current to August 2016. Ten studies reported on the recurrence of peritonsillar abscess (our main outcome). Most of them did not clearly define 'recurrence' and they varied in the timing of its assessment, however we were able to combine (pool) the data from these studies. When we pooled the data the recurrence rate was higher in the needle aspiration group compared with incision and drainage. It is important to note that the evidence for this outcome was of very low quality. Some studies found that patients had more pain when they had incision and drainage. We identified problems or potential problems in all of the included studies. The most important of these was that the studies did not all assess recurrence in the same way, at the same time, using the same criteria. The quality of the evidence for all of the outcomes that we looked at was very low.
The evidence is current to February 2017. We looked for studies that randomly allocated people with APS to different treatments, including anticoagulants, antiplatelets, or both. We identified five studies involving 419 participants. The average age of the participants was between 41 and 50 years, and the studies included people with previous stroke or previous blood clots in large veins or arteries. Studies took place in eight different countries and had a variety of funding sources. One trial compared a novel anticoagulant (rivaroxaban) with the standard anticoagulant (warfarin). Two studies compared a high dose versus standard dose of warfarin , and two studies compared combinations of antiplatelets, anticoagulants, or both. Interventions lasted from 180 days to an average of 3.9 years (SD 2.0). In one study with an anticoagulant (rivaroxaban), participants had no episodes of blood clotting, and there was no difference in the risk of bleeding (moderate-quality evidence). In the two studies comparing higher and lower doses of anticoagulant (warfarin), similar proportions of participants had blood clotting and major bleeding problems (low-quality evidence), but the higher dose warfarin group had a greater risk of minor bleeding problems and any bleeding problems (low-quality evidence). The two studies comparing combinations of antiplatelets and anticoagulants were both small, not well reported, and their results were inconclusive (very low-quality evidence). One study was well designed, and we judged it to be at low risk of bias; we judged a second study to be at low risk of bias for the main results. We considered all other studies to be at unclear or high risk of bias because of concerns about their methods or reporting of results. All the results were imprecise and did not clearly indicate benefit or harm. We did not find enough evidence in our review to judge the benefit or harm of using anticoagulant (rivaroxaban) versus anticoagulant (warfarin) for preventing blood clots or stroke in people with APS. Treatment with high doses of the anticoagulant warfarin was associated with a higher risk of minor and any bleeding than treatment with standard doses, but we found no difference in terms of benefit. There was not enough evidence to show benefit or harm of any combination of anticoagulants and/or antiplatelets. Five ongoing studies will likely provide additional evidence in the near future.
We included six randomised clinical trials (where people are randomly allocated to one of two groups) with 173 participants. All participants had cirrhosis. Interventions consisted of different types of exercise including bicycling, treadmill walking, and weight lifting. Programmes were home-based or supervised and lasted between eight and 14 weeks. Physical exercise did not seem to affect mortality (death), side effects or quality of life. Overall, the evidence for the effect of physical exercise was of low or very low quality. Factors that downgraded the quality of the evidence included lack of trials with a low risk of bias, small trials, and not similar results across trials.
In the present Cochrane systematic review, we assessed the benefits and harms of prothrombin complex concentrate in vitamin K antagonist-treated bleeding and non-bleeding patients who are undertaking acute surgical intervention. We searched the databases until 1 May 2013. We identified four randomized trials (453 participants) involving neurological and cardiac surgical settings, as well as medical reversal of vitamin K-intoxication among participants. We found six ongoing trials but were unable to retrieve these data. We reran the search in October 2014 and found one new study of potential interest. We added this study to a list of ‘Studies awaiting classification', and we will incorporate this study into the formal review findings at the time of the review update. We could not identify any beneficial effects of prothrombin complex concentrate on death. In our predefined outcomes, we identified a decreased volume of fresh frozen plasma transfused for reversal of vitamin K antagonist treatment. We could not identify statistical differences in reduced blood loss, harm or numbers of adverse events in the group treated with PCC. However, all trials were of low quality and small, and all were characterized by a high level of heterogeneity. Therefore, evidence in support of PCC in vitamin K antagonist-treated bleeding and non-bleeding patients receiving acute surgical intervention remains weak.
We analysed 32 studies that involved a total of 2601 participants. Most trials involved people with diabetic gastroparesis, who received short-term treatment (often four weeks). Non-profit funding bodies (the Chinese government and a university) funded six out of the 32 studies and the others did not report the funding source. One study compared real acupuncture with sham acupuncture (needling on non-acupuncture points). Twenty-eight trials compared acupuncture to a drug, or acupuncture with a drug or to the drug alone. A small number of trials compared acupuncture plus a non-drug treatment to the same treatment alone. The drugs in the trials were mostly gastrokinetic agents (such as domperidone, mosapride, and cisapride), which promote stomach emptying. Despite there being a small reported effect, we are uncertain about any benefit of acupuncture for symptomatic gastroparesis in the short term, when used alone or added to other treatments for gastroparesis (gastrokinetics, other medicines, or 'routine care'), due to the evidence being of very low certainty. There is no information to help understand any long-term benefits of acupuncture. The effects of acupuncture on symptoms of gastroparesis are probably little different from those of sham acupuncture in the short term. It is unclear whether acupuncture helps in gastroparesis after surgery or when the cause of gastroparesis is unknown, because there is not enough information. No trial studied the effects of acupuncture on quality of life or delayed emptying of the stomach. We do not know whether acupuncture is safe for people with diabetes who have delayed emptying of the stomach, because safety was incompletely reported in most trials. Overall, the certainty of evidence is very low. Most studies had design issues. We suspected the existence of unpublished studies and it was not possible to be sure whether those we identified fully reported their findings. There was no consistent definition of improvement across studies. Any reported benefit may not be accurate and should be interpreted with caution. Future trials should focus on valid measures of treatment effects reported directly by patients, and assessment of stomach emptying. Trials should meet quality standards for design and transparent reporting. The evidence is current to March 2018.
We searched the literature up to December 2017 and found 12 studies (743 individuals) that met our inclusion criteria. Flexibility interventions were compared with control (treatment as usual), aerobic training interventions (e.g. treadmill walking), resistance-training interventions (e.g. using weight machines that provide resistance to movement), and other interventions (e.g. Pilates). The average age of participants was 48.6 years. Trials were conducted in seven countries, and most studies (58.3%) included only female participants. Exercise trials ranged from 4 to 20 weeks. The stretching exercise programs ranged from 40 to 60 minutes, 1 to 3 times a day. The intensity of the stretches (e.g. how far the stretch was taken in the available range of motion) was not reported in most cases. The time each stretch was held ranged from 6 to 60 seconds. The targeted muscles were usually of both the upper and lower extremities, neck, and back. The flexibility training was either supervised or done at home. Our main comparison was flexibility exercise versus land-based aerobic training. Key results at the end of treatment for our main comparison Compared with land-based aerobic exercise training, flexibility exercise resulted in little benefit at 8 to 20 weeks' follow-up. Each measure below was measured on a scale from 0 to 100, with lower scores better. Health-related quality of life: People who received flexibility exercise training were 4% worse (ranging from 6% better to 14% worse). • People who had flexibility training rated their quality of life as 46 points. • People who had aerobic training rated their quality of life as 42 points. Pain intensity: People who received flexibility exercise training were 5% worse (ranging from 1% better to 11% worse). • People who had flexibility training rated their pain as 57 points. • People who had aerobic training rated their pain as 52 points. Fatigue: People who received flexibility exercise training were 4% better (ranging from 13% better to 5% worse). • People who had flexibility training rated their fatigue as 67 points. • People who had aerobic training rated their fatigue as 71 points. Stiffness: People who received flexibility exercise training were 30% better (ranging from 8% better to 51% better). • People who had flexibility training rated their stiffness as 49 points. • People who had aerobic training rated their stiffness as 79 points. Physical function: People who received flexibility exercise training were 6% worse (ranging from 4% better to 16% worse). • People who had flexibility training rated their physical function as 23 points. • People who had aerobic training rated their physical function as 17 points. Withdrawal from treatment A total of 18 per 100 people dropped out of the flexibility exercise training group for any reason compared to 19 per 100 people from the aerobic training group. Harms We found no clear information on harms. One study reported that one participant had swelling (tendinitis) of an ankle tendon (Achilles), but it is unclear if this was related to participation in the flexibility exercise. Quality of evidence The evidence does not show that flexibility exercise significantly improves health-related quality of life, pain, fatigue, or physical function. The number of people dropping out from each group was similar. Although the evidence suggests that flexibility exercise improves stiffness, caution is advised in interpretation of these results, as this improvement was seen in only one study with very few participants. We considered the overall certainty of the evidence to be low to very low due to study design issues, the small number of participants, and low certainty of results.
We searched for studies using multiple research databases, conference research abstracts, and by contacting experts in the field. The evidence is current to August 2016. We only considered studies with participants being sedated for procedures in the emergency department. We only included studies that compared capnography and standard monitoring to standard monitoring only. The main outcomes involved events of low blood oxygen content, low blood pressure, and vomiting. We also recorded how many times the healthcare providers had to help the patient breathe easier. This could mean simple actions such as opening of the mouth to more serious manoeuvres such as mechanically breathing for the patient. Three studies with 1272 people, containing moderate evidence, were included in our study. There was no difference in heart, lung, or airway complications with the addition of capnography. When only adults were studied, healthcare providers performed more manoeuvres to help the patient breathe when capnography was used. This could be due to false alarms. The level of evidence was determined to be moderate.
Authors from Cochrane Oral Health carried out this review and the evidence is up to date to 27 February 2018. We included 38 studies and a total of 1042 infrabony defects. We considered four different types of surgical treatments and compared each technique with the same one when APC was added. Overall we considered these comparisons: open flap debridement with APC versus without APC; open flap debridement and bone graft with APC versus without APC; guided tissue regeneration with APC versus without APC; and enamel matrix derivative with APC versus without APC. There is very low-quality evidence that the addition of APC to two types of treatment: open flap debridement and open flap debridement with bone graft, may bring some advantages in the treatment of infrabony defects. However, for the other two types of treatment, guided tissue regeneration and enamel matrix derivative, there is insufficient evidence of a benefit. We judged the quality of the evidence to be very low due to problems with the design of the studies.
The evidence is current to July 2015. We conducted a review to compare short- and long-term surgical complications (such as scar tissue forming around the implant and squeezing it - referred to as 'capsular contracture', and 'implant rupture'), cosmetic outcomes, women's postoperative quality of life and satisfaction with different types of breast implants used in breast reconstruction. We found five randomised studies involving 202 women that provided data for five different comparisons: rough versus smooth surface, implant filler materials compared to each other (silicone versus saline, and hydrogel versus saline), anatomical versus round shape, and variable- versus fixed-volume. Four studies included women who received a mastectomy for breast cancer and one study included women who had bilateral mastectomies for preventive purposes. The authors of two studies reported that they did not have competing interests; the authors of three studies did not report this information. Three studies reported that their studies received financial support from research foundations; the other studies did not report any information regarding the source of their funding. Only two studies reported differences between types of implants for some of the outcomes we considered. One study on 65 women compared silicone-filled implants with saline-filled implants and showed that saline implants resulted in fewer cases of capsular contracture and a higher number of women who were satisfied with the reconstructed breast. However more women in the saline-filled implant group required further operations on the reconstructed breast than in the silicone-filled implant group. Another study on 40 women compared variable-volume implants (inserted in a single surgical procedure) with fixed-volume implants (inserted in the second of two separate surgical procedures) and showed that there were significantly higher satisfaction levels and significantly lower reoperation rates with the fixed-volume implants. The remaining three studies reported on the following comparisons: rough versus smooth silicone-filled implants (20 women), PVP-hydrogel versus saline-filled implants (41 women) and anatomically shaped versus round implants (36 women). These studies reported no differences between implant types for outcomes such as capsular contracture, other short-term complications or reoperation rates. There were no studies that compared recent generation silicone implants with earlier versions or implants from different manufacturing companies. The evidence we found was limited: only a negligible, tiny fraction of women who undergo breast reconstruction have been studied in randomised controlled trials. The quality of evidence is very low, as the studies we identified suffered from major methodological limitations. Despite the fact that several million women have had their breasts reconstructed over the last 20 years, the small number of studies and the low numbers of women included in these studies does not allow us to draw any definitive conclusions about the which is the best type of breast implant. This lack of evidence should be discussed when informing women about the risks and complications of different implant-based breast reconstruction options. There is a need for further studies, which include a larger number of women and compare different types of implants, to free women from decisions made on the basis of surgical opinion alone.
This review looked for evidence of MD rehabilitation in adults with multiple sclerosis. The authors concluded there was strong evidence that inpatient or outpatient rehabilitation can lead to improvement in activity (disability) and in overall ability to participate in society, even though there is no reduction in actual impairment. There was limited evidence for short-term improvements in symptoms and disability, and in participation and quality of life with the high intensity outpatient and home-based rehabilitation programmes. For low intensity programmes conducted over a longer period there were longer term gains in quality of life; and for benefits to carers in terms of general health and engagement in social activities. The evidence available for other aspects of MD rehabilitation, including outpatient and home based therapy is not yet sufficient to allow many conclusions to be drawn.
This review is based on five studies involving 1065 women undergoing CS. The studies were of moderate quality. The included studies did not use this review's criteria for diagnosis for UTI, so there are no data for this primary outcome. When considering UTI, as defined by the trial authors, there were no clear differences between groups. There were no data relating to bladder injury during the CS (the review's other primary outcome). Our analysis showed that the use of urinary catheter was associated with less retention of urine after CS. On the other hand, pain/discomfort due to catheterisation or at first voiding after CS, time to ambulate and hospital stay favoured non-use of urinary catheter. There was no difference in the incidence of uterine bleeding due to uterine atony (relaxation of the uterus) after the delivery. The limited evidence in this review is based five trials of moderate quality and results should be considered in this context. There is not enough evidence to assess the routine use of indwelling bladder catheters in women undergoing CS. There is a need for more rigorous research on this topic and future trials should use a standardised criteria for the diagnosis of UTI and other common outcomes.
The review includes 50 randomised controlled trials that compare antioxidants with placebo or with no treatment/standard treatment, or with another antioxidant, in a total of 6510 women. Funding sources were reported by only 14 of the 50 included trials. Very low-quality evidence suggests that antioxidants may be associated with an increased live birth and clinical pregnancy rate. Based on these results, we would expect that out of 100 subfertile women not taking antioxidants, 20 would have a baby, compared with between 26 and 43 women per 100 who would have a baby if taking antioxidants. There was insufficient evidence to draw any conclusions about the adverse effects of miscarriage, multiple births or gastrointestinal effects. Very low-quality evidence suggests that pentoxifylline may also be associated with increased rates of clinical pregnancy, but there were only three trials in this analysis. In this case we would expect that out of 100 subfertile women not taking pentoxifylline, 25 would become pregnant, compared with between 28 and 53 women per 100 who would become pregnant if taking pentoxifylline to improve their chances of getting pregnant. There was also insufficient evidence to draw any conclusions about the adverse effects of pentoxifylline. Only one trial measured one antioxidant against another,so there was no evidence available to draw any conclusion from this comparison. The overall quality of evidence was limited by serious risk of bias associated with poor reporting of methods, imprecision and inconsistency.
No randomized controlled trials (RCTs) can be found comparing the effect of SCUs against traditional nursing units in managing agitated behaviours in people suffering from dementia. This review has examined the results of non-RCTs. The findings about the outcomes of this review arise just from one study except for the outcome of "physical restraint use" at 6 months, which includes data from two studies. Selection bias is a major problem in non-RCTs, and confounds the limited evidence that favoured SCU care with regard to a decrease in agitated behaviour and in the use of physical restraints. A convincing case for the benefits of SCU care cannot be made and further studies are necessary.
This review looks at vaccines targeted at the 'pre-erythrocytic' phase of the parasite's life, the phase before the parasites first enter the bloodstream from the liver. Trials of four types of vaccine against P. falciparum, the most important human malaria species, were available for this review. One of these (the RTS,S vaccine) significantly reduced the number of episodes of clinical malaria and severe malaria in children, while the other three vaccines were not effective under the conditions of the trials. No severe adverse events observed following the RTS,S vaccination were judged to be related to vaccination, though minor adverse events like headache, swelling, and malaise were.
We searched various sources up to 29 August 2017 and included 13 studies that involved 67,688 people with atrial fibrillation who received either a factor Xa inhibitor or a vitamin K antagonist. All included people were adults and on average aged between 65 and 74 years. Approximately one-third were women. We found that factor Xa inhibitors when compared with warfarin, which was used as comparator in all trials, reduced the number of strokes in people with atrial fibrillation. This reduction was, however, rather small. Factor Xa inhibitors also appeared to reduce the number of serious bleedings (including those into the brain) and the number of people dying from any cause compared with warfarin. We considered the quality of evidence in our review as moderate to high. The studies that we included were generally large to very large. We found that the results from the larger studies were generally similar and this strengthened our findings. Finally, we are confident that we included all relevant studies in our review and did not miss any important studies.
We searched for randomised controlled trials (RCTs), in which participants were randomly assigned to a treatment group or a control group. In most settings these studies provide the highest quality evidence. We were interested in studies that compared a sodium channel blocker with placebo, or used it as an add-on to any approved treatments for MS. We found only one study including a total of 120 participants. No data were found on disability progression and people who experienced relapses. No significant difference between two groups was found in measurements of cerebral atrophy, expanded disability score changes, or MS functional composite score changes. Treatment with lamotrigine was associated with more rashes (20% versus 5%) and transient, dose-related deterioration of mobility. There is a lack of evidence to address the review question on the efficacy of sodium channel blockers for people with MS. This review will be updated when the three ongoing studies we identified are completed. The quality of evidence was judged as very low due to the low number of available studies and included population. There is a lack of evidence to address the review question on the efficacy of sodium channel blockers for people with MS. Assessment of the three ongoing trials might change this conclusion. Further high-quality large-scale studies are needed.
The evidence is current to June 2015. It includes the results from 27 studies of 73,557 children. It included boys and girls aged four to 18. The studies compared injury prevention education with either the usual curriculum or an alternative programme unrelated to injuries. The studies we included were aimed at preventing a range of injuries. We excluded programmes that focused on just one cause of injury. The review measured the effects of the educational programmes on the occurrence of injuries in children, their safety skills, behaviour and knowledge. The review also looked at whether school-based approaches are good value for money. Only a few studies reported the effect on injury occurrence in children and so these effects were inconclusive. This does not mean that school-based programmes are ineffective but rather that more evidence is needed. The review did find evidence that school-based injury prevention education programmes can improve children's safety skills, safety behaviours and safety knowledge. However, the evidence was inconsistent, with some studies showing a positive effect and others showing no effect. Only one study reported on how cost-effective school-based programmes were and so again it is difficult to draw conclusions from this evidence alone. The studies were generally of poor quality for all the measurements of effectiveness of the programmes but particularly for behaviour and knowledge. This is because information about how the study was conducted was not usually reported very clearly in the study reports or there were major flaws in the way that the studies were undertaken. More research is needed that is of higher quality.
Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 10 May 2017. It includes 35 studies (published between 1993 and 2017) with 3102 participants, all patients being treated for cancer, aged from 1 to 87 years old. Review authors included studies comparing cytokines and growth factors for the prevention of oral mucositis. The studies were carried out all over the world and often featured multiple sites, although most took place in high-income countries. The main findings were regarding keratinocyte growth factor (KGF). KGF is likely to reduce the risk of oral mucositis in adults who are receiving either radiotherapy to the head and neck with chemotherapy (cisplatin or fluorouracil), or chemotherapy alone for mixed solid and blood cancers. KGF may also reduce the risk of oral mucositis in adults receiving bone marrow/stem cell transplant after conditioning therapy for blood cancers, but these results are less clear because of multiple complicating factors. KGF appears to be a relatively safe intervention. There did not appear to be any serious adverse effects of any of the interventions assessed in this review. Due to limited research, review authors are uncertain of any beneficial effects of other cytokines and growth factors. There is currently insufficient evidence to draw any conclusions about the use of cytokines and growth factors in children. For reducing oral mucositis in adults receiving radiotherapy to the head and neck with chemotherapy, review authors rated the evidence for KGF as moderate to high quality. For reducing oral mucositis in adults receiving chemotherapy alone for mixed solid and blood cancers, they rated the evidence for KGF as low to moderate quality. This evidence was downgraded due to there not being enough data and because some results have not yet been published. For reducing oral mucositis in adults receiving bone marrow/stem cell transplant after conditioning therapy for blood cancers, they rated the evidence for KGF as low quality because results were not similar across the studies and some results have not yet been published. Evidence on side effects of KGF was poorly reported and inconsistent.
We included 12 studies. Six studies evaluated the effectiveness of educational materials alone; one study evaluated the effectiveness of educational meetings; and four studies evaluated a combination of the two in increasing the reporting of occupational diseases by physicians. A further study evaluated the effectiveness of a complex educational campaign acting at society level. We searched for studies until January 2015. We found that the use of educational materials did not considerably increase the number of physicians reporting occupational diseases, but a legal obligation reminder message did. Furthermore, we found that the use of educational materials did not considerably increase the rate of reporting occupational diseases. Similarly, we found that the use of both educational materials and meetings did not considerably increase the number of physicians reporting occupational diseases or the rate of reporting. The same holds for the use of educational meetings alone. The use of an educational campaign appeared to increase the number of physicians reporting occupational diseases, although this was based on very low-quality evidence. We need high-quality studies to clarify the effectiveness of these interventions. This review was unable to determine the effectiveness of interventions other than education like the use of financial incentives, which could be an important form of motivation in changing physicians' behaviour. Such small-scale interventions could be investigated using larger randomised controlled trials, while the evaluation of large-scale interventions like legislation should use an interrupted time-series design.
We searched several medical databases and trial registries up to January 2013 and contacted researchers. We found one study that looked at the comparison we were interested in. This study was potentially biased, mainly because the care providers, parents and children were aware of the type of pain relief the children received. The study was small, involving 55 children aged 16 months to 15 years, and showed that the children who received one of the two main types of nerve block tended to have less pain after 30 minutes than those who received intravenous morphine for initial pain control. The nerve blocks led to some pain and redness at the injection site in a few cases, while intravenous morphine caused more serious problems such as depressed breathing (lack of oxygen), excessive sleepiness and vomiting in a small number of children. Moreover, children who had nerve blocks continued to have lower pain scores over a six-hour period with less need for additional pain relief. There was insufficient evidence to determine whether children or parents were more satisfied with one method of pain relief than the other. Use of resources (e.g. nursing time, cost of medications) was not measured. The quality of the study included in this review was low and so these conclusions are not certain. Further well designed studies investigating whether nerve blocks are more effective and safer than other means of pain relief are needed.
We included 26 randomised controlled trials (RCTs) trials with 2084 participants that looked at treatments for first-episode genital herpes versus placebo or another treatment. The trials all included people who were having their first episode of genital herpes and were conducted in various countries around the world. Three of the trials included only women, and in all the trials the participants had had symptoms for eight days or less. Fifteen of the 26 trials were funded by a pharmaceutical company.Key resultsThe evidence is current to April 2016. The evidence shows that oral and intravenous acyclovir may be effective in reducing the number of days of symptoms in someone with first-episode genital herpes. Oral valaciclovir showed a similar length of symptom duration as acyclovir. We did not find enough evidence to support the use of topical treatments. There was also no evidence that any of the treatments reduced the time between episodes for people with genital herpes. The evidence presented here is mostly of low quality. The studies included were mainly conducted in the 1980s and at this time the brief way studies were reported does not allow us to adequately judge the quality of the included studies.Quality of the evidenceThe evidence provided by this review is of low quality. Although there are 26 included studies, the meta-analyses created in this review at the most, had three included studies. This was mainly due to the low number of studies that looked at each different type of antiviral. It was also unclear as to how well the included studies were conducted, as the methods for each of the individual studies did not report enough detail to judge each study's quality, inconsistence and this also affected the overall quality of the review.
Cochrane Oral Health provided the search strategies and carried out the search in several electronic databases. We selected nine randomised trials for inclusion in this review that were conducted between 1998 and 2014. The evidence in the review is up to date as of 22 June 2016. The trials involved a total of 662 participants, with 1498 teeth treated. Three studies were conducted in the USA, one in Taiwan, one in China, one in Bulgaria, one in Germany, one in Turkey and one in the UK. The population consisted of both children and adolescents in four trials, only adults in four trials, and both children/adolescents and adults in one trial. Despite the number of included studies, only a few trials adequately and completely reported information on the primary outcomes. Two trials reported on removal of decay, and there was not enough evidence to conclude that either lasers or drills were better at decay removal. Only five trials reported on episodes of pain, which was significantly reduced in people treated with lasers. There was no difference in terms of side effects, such as inflammation or death of dental pulp, between the two interventions. The overall quality of the evidence for the nine studies was low. Only one study adequately randomised participants, and none of the included studies was at low risk of bias. This review highlights the need for high-quality studies comparing laser therapy and mechanical drills in the treatment of dental decay.
The review found that patients treated within a care pathway may be less likely to suffer some complications (e.g. urine infections), and more likely to have certain tests (e.g. brain scans). However, the use of care pathways may also reduce the patient's likelihood of functioning independently when discharged from hospital, their quality of life, and their satisfaction with hospital care. Currently, there is not enough evidence to justify introducing care pathways for the routine care of all patients with stroke. Further research is needed to find out if care pathways for stroke do more good than harm.
The results of this systematic review show that driver education in schools leads to early licensing. They provide no evidence that driver education reduces road crash involvement, and suggest that it may lead to a modest but potentially important increase in the proportion of teenagers involved in traffic crashes.
Our search strategy is up to date as of July 2017. We found four trials looking at three different types of tools to help improve the amount of tumour that is removed. The tumour being evaluated was high-grade glioma. Imaging interventions used during surgery included: • magnetic resonance imaging (iMRI) during surgery to assess the amount of remaining tumour; • fluorescent dye (5-aminolevulinic acid) to mark out the tumour; or • imaging before surgery to map out the location of a tumour, which was then used at the time of surgery to guide the surgery (neuronavigation). All the studies had compromised methods, which could mean their conclusions were biased. Other studies were funded by the manufacturers of the image guidance technology being evaluated. We found low- to very low-quality evidence that use of image-guided surgery may result in more of the tumour being removed surgically in some people. The short- and long-term neurological effects are uncertain. We did not have the data to determined whether any of the evaluated technologies affect overall survival, time until disease progression, or quality of life. There was very low-quality evidence for neuronavigation, and we identified no trials for ultrasound guidance. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly than conventional surgery. Evidence for intraoperative imaging technology for use in removing brain tumours is sparse and of low to very low quality. Further research is needed to assess three main questions. 1. Is removing more of the tumour better for the patient in the long term? 2. What are the risks of causing a patient to have worse symptoms by taking out more of the tumour? 3. How does resection affect a patient's quality of life?
The purpose of this review was to assess which of these two medications was the best for initial treatment for people living with HIV, and through our search we identified two randomised controlled trials. We did not find any critical difference between the two medications in regards to serious adverse events or virologic response, but did find that TDF is superior to AZT in terms of immunologic response and adherence and more frequent emergence of resistance. However, these two studies are not directly comparable because they used two related different drugs in addition to TDF and AZT. Future studies and recommendations should focus on specific toxicities and tolerability when comparing these two medications.
This is a review of the clinical trials that compared patients initially prescribed one of the two anti-rejection drugs after liver transplantation. Sixteen trials (3813 participants) were included. The review shows that tacrolimus is marginally better than cyclosporin at preventing patient death and graft loss. Tacrolimus is substantially better than cyclosporin at preventing rejection. No differences were seen between the drugs with respect to adverse events (renal failure, lymphoproliferative disorder) except for diabetes mellitus, which was more common with tacrolimus. After liver transplantation more patients stayed on tacrolimus than on cyclosporin. Tacrolimus is more beneficial than cyclosporine and should be considered the treatment of choice after liver transplantation. This review does not evaluate the benefit or harm of switching from one anti-rejection drug to another.
We included four randomised controlled trials with a total of 1305 participants. A total of 543 participants were randomised to total or near-total thyroidectomy and 762 participants to subtotal thyroidectomy. Two trials had a duration of follow-up between 12 and 39 months and two trials a follow-up of 5 and 10 years, respectively. Most participants were women and the average age was around 50 years. In the short-term period after surgery no deaths were reported for both total thyroidectomy and subtotal thyroidectomy groups, however longer-term data on all-cause mortality were not reported. Goitre recurrence was lower for total thyroidectomy compared to subtotal thyroidectomy: the risk for goitre recurrence was 84 per 1000 trial participants for subtotal thyroidectomy and 5 per 1000 participants (with a possible range of 1 to 19) for total thyroidectomy. There was no clear benefit or harm of either surgical technique for re-operations because of goitre recurrence, side effects like permanent recurrent laryngeal nerve palsy or development of thyroid cancer. No data on health-related quality of life or socioeconomic effects were reported in the included trials. The overall quality was low to moderate, mainly because of the small number of studies and participants as well as low rates of events which makes distinction between harms and benefits of the two surgical techniques difficult. This evidence is up to date as of June 2015.
We searched for studies that had included people with alcohol or drug problems and that had divided them by chance into MI or a control group that either received nothing or some other treatment. We included only studies that had checked video or sound recordings of the therapies in order to be certain that what was given really was MI. The results in this review are based on 59 studies. The results show that people who have received MI have reduced their use of substances more than people who have not received any treatment. However, it seems that other active treatments, treatment as usual and being assessed and receiving feedback can be as effective as motivational interviewing. There was not enough data to conclude about the effects of MI on retention in treatment, readiness to change, or repeat convictions.The quality of the research forces us to be careful about our conclusions, and new research may change them.
Two studies were included in this review. Both were of moderate methodological quality and evaluated the effectiveness of educating children on preventing dog bite injuries. Both studies involved a 30-minute lesson. One study additionally compared the effect of educating the children's parents through a leaflet. One study videotaped the way children behaved when exposed to an unknown dog, and their behaviour was observed. The main outcome reported in both studies was a change in behaviour. It is unclear from this review whether educating children can reduce dog bite injuries as dog bite rates were not reported as an outcome in either of the included studies. The effect of educating children and adolescents in settings other than schools has not been evaluated. There is a general lack of evidence about the impact of education to prevent dog bites in children and adolescents, therefore further studies that look at dog bite rates after an intervention are recommended. Education of children and adolescents should not be the only public health strategy to reduce dog bites and their dramatic consequences.
We included 4745 participants from 21 trials who received iron injections, iron tablets or no treatment. Clinical settings of these trials included loss of blood, cancer, anaemia before surgery for various reasons and heart failure, among others. Most trials included participants with mild to moderate anaemia and excluded participants who were allergic to iron therapy. Comparisons between iron tablets and no treatment revealed no evidence of clinical benefit in terms of a decrease in death or in quality of life. However, a reduction in the proportion of participants who required blood transfusion was noted among those who received iron tablets versus no treatment. Haemoglobin levels were higher in participants receiving iron tablets versus no treatment. With regards to iron injections, haemoglobin levels were higher after iron injections compared with levels reported after iron tablets or no treatment, but no evidence showed clinical benefit in terms of a decrease in death, in the number of participants requiring blood transfusion or in quality of life of participants. Although the average amount of blood transfused was less in the iron injection group than in the iron tablet group, only one trial reported this outcome, introducing significant doubt about this finding. Differences in serious complications between people who received iron versus no treatment were imprecise. No trials reported severe allergic reactions due to iron injections, suggesting that these are rare. Most of the adverse events related to iron tablet treatment were mild; effects such as nausea, diarrhoea and constipation were reported. Comparisons of the clinical benefit of one iron preparation over another were imprecise. We were unable to determine whether iron is useful in specific clinical situations because available information was not clearly presented. In summary, no evidence is currently available to support the routine use of iron injections in adult anaemic men and or in adult non-pregnant anaemic women who have not just given birth to a baby. Iron tablets might be useful in anaemic adult men and adult women who can tolerate the side effects. No evidence suggests any advantage of one iron preparation over another. Additional randomised controlled trials are required to determine whether iron treatment decreases death and blood transfusion requirements and improves quality of life. Such trials should be appropriately designed and should include a sufficiently large number of participants, to decrease the chance of erroneous conclusions.
We searched and identified 17 randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method), published before October 2018. All were conducted in Europe, and collectively included 3488 children. Twelve trials included children who were not prone to acute middle ear infections, whilst five trials included children who were prone to such infections. One-third fewer children not prone to acute middle ear infection who took probiotics experienced acute middle ear infections compared to children not taking probiotics. However, probiotics may not benefit children prone to acute middle ear infection. Taking probiotics did not impact on the number of days of school that children missed. None of the studies reported on the impact of probiotics on the severity of acute middle ear infection. There was no difference between the group taking probiotics and the group not taking probiotics in the number of children experiencing adverse events (harms). The quality (or certainty) of the evidence was generally moderate (meaning that further research may change our estimates) or high (further research is unlikely to change our estimates). However, the trials differed in terms of types of probiotics evaluated, how often and for how long they were taken, and how the trial results were reported.
We included 18 trials that compared HS to IS in people undergoing surgery. The trials included 1087 participants. Five hundred and forty-five (545) participants received HS and 542 received IS during their operations. The participants were randomly assigned to their groups. The studies took place in 11 countries. Study participants were over the age of 18. All studies excluded people with serious health risks from participating. All studies monitored fluid levels during the operation and up to three days after. There were seven deaths in total, three (less than 1%) from the IS group and four (less than 1%) from the HS group. The risk of death was very low in these studies. The studies did not report the occurrence of serious adverse events. Thirteen studies reported the amount of fluid given. The IS group received a mean of 2.4 L and the HS group received 0.91 L less (1.49 L). The highest amount of sodium in the blood over the course of the study was reported by 16 studies. The IS group had a median of 139 meq/L and the HS group was 7.73 meq/L higher. The normal acceptable range is 136 to 146 meq/L. For deaths and adverse events the trials lacked sufficient size and duration to adequately assess differences. We assessed the quality of evidence for deaths to be very low, and future studies are likely to change the result reported here. The reporting of the highest amount of sodium is of moderate quality. The measuring of blood sodium during an operation is a common measurement that is unlikely to be misrepresented.
This review is up-to-date as of September 2016. We included five trials involving 4197 people; all trials assessed glyceryl trinitrate, a drug that is given as a skin patch and which releases nitric oxide. One study was international, whilst the remainder were studies performed at single centres. Not all trials contributed data to all outcomes. We used both unpublished and published information, where available. We did not find any trials assessing other nitrate drugs, L-arginine, or nitric oxide synthase inhibitors. Overall, glyceryl trinitrate did not improve the rate of death or dependency compared with those who did not receive glyceryl trinitrate after acute stroke. Glyceryl trinitrate did not improve other outcomes including death and quality of life. Glyceryl trinitrate lowers blood pressure, and increases heart rate and headache in people with acute stroke. The key results are based on high-quality evidence. There is currently insufficient evidence to recommend the use of drugs affecting nitric oxide production in acute stroke. Overall, glyceryl trinitrate is inexpensive, lowers blood pressure, increases heart rate and headache, but does not change clinical outcomes in people who have suffered a stroke.
Epidemiological or observational studies were used to see if taking a blood pressure lowering drug reduces the risk of developing PD in the general population. Only six studies were found. Three studies of the same design looked at the same classes of blood pressure lowering drugs but used different methods so the results could not be combined. Clinical trials were used to see if taking a blood pressure lowering drug when you already have PD reduces symptoms or slows disease progression. Only two completed trials were found, all reporting the effects of different classes of drugs. One trial of a drug belonging to the group called calcium channel blockers is still underway and the results, which are due in 2012, will help inform further studies. Very little information was found for either primary or secondary prevention. More studies are needed to look at different blood pressure lowering drugs and their effects on the risk of developing PD. From these studies, particular potential drugs will be identified to go forward for clinical trials in patients who have PD, to see if they improve symptoms or slow down the disease. It is important that we have more information about the side effects for people with PD who are taking these drugs and that any benefits far outweigh any harms.
Our review found 15 studies that compared a combination of ICS/LABA with ICS alone. We found that on the whole, combination inhalers reduced the frequency of flare-ups (not including hospitalisations) compared with ICS alone. The studies showed that on average, the number of exacerbations per participant was reduced, as was the probability of death, during treatment. Quality of life and lung function showed improvement with combination treatment compared with ICS, but no difference between them was noted in terms of adverse effects, or the likelihood of having no flare-ups at all. Future research should assess the efficacy of BDF and MF/F because most evidence gathered to date, including for mortality, has been drawn from FPS studies.
This is a systematic review of clinical research testing whether taking the antibiotic can prevent infection from a water-borne bacteria called Leptospira. Data from different trials had conflicting results, and these trials targeted different kinds of people - travellers and people who live in at risk areas, encompassing soldiers, farmers, and students. Taken together, the data does not support the practice in all cases, though short term travellers with a potential for high risk exposure may be helped. People who took doxycycline were more likely to have stomach pain, nausea, and vomiting but the medication had to be stopped in only a few participants.
Cochrane review authors searched medical databases for clinical trials. They found two completed RCTs that assessed the effects of cell-based therapy over a six-month follow-up period. One study was not fully published and did not provide numerical data. Both studies were funded by stem cell companies. One study, which included 64 people with ALS/MND, provided data. The people taking part in the trial had an average time since symptom onset of about two years. They had mild to moderate problems with motor function (ability to perform physical tasks) at the start of the trial (with an average of 35 on the ALS Functional Rating Scale-revised, on which a score of 0 indicates greatest impairment and 48 is normal function). The study provided low-quality evidence that stem cells obtained from people's own bone marrow (the cells in the centre of bone) did not result in significant side effects. The cell implantation procedure was well tolerated. Based on evidence from this trial, stem cell treatment may slightly reduce decline in motor function at six months, but may not improve breathing or quality of life at four months, or overall survival at six months. Based on the very limited evidence available, any benefit is uncertain due to there being only one poorly conducted study and results within the study varies. We urgently need large, well-designed clinical trials to establish whether or not cell-based therapies have a clear clinical benefit in ALS/MND. Major goals of future research are to identify the right type and amount of cells to use, and how best to administer them. The evidence is up to date as of July 2019.
Several trials have studied the effects of milk thistle for patients with liver diseases. This systematic review could not demonstrate significant effects of milk thistle on mortality or complications of liver diseases in patients with alcoholic and/or hepatitis B or C liver diseases combining all trials or high-quality trials. Low-quality trials suggested beneficial effects. High-quality randomised clinical trials on milk thistle versus placebo are needed.
The evidence is current to September 2015. We found and included 57 studies involving 3002 people with aphasia in our review. We reviewed all SLT types, regimens, and methods of delivery. Based on 27 studies (and 1620 people with aphasia), speech and language therapy benefits functional use of language, language comprehension (for example listening or reading), and language production (speaking or writing), when compared with no access to therapy, but it was unclear how long these benefits may last. There was little information available to compare SLT with social support. Information from nine trials (447 people with aphasia) suggests there may be little difference in measures of language ability. However, more people stopped taking part in social support compared with those that attended SLT. Thirty-eight studies compared two different types of SLT (involving 1242 people with aphasia). Studies compared SLT that differed in therapy regimen (intensity, dosage and duration), delivery models (group, one-to-one, volunteer, computer-facilitated), and approach. We need more information on these comparisons. Many hours of therapy over a short period of time (high intensity) appeared to help participants' language use in daily life and reduced the severity of their aphasia problems. However, more people stopped attending these highly intensive treatments (up to 15 hours a week) than those that had a less intensive therapy schedule. Generally, the quality of the studies conducted and reported could be improved. Key quality features were only reported by half of the latest trials. Thus, it is unclear whether this was the result of poorly conducted studies or poorly reported studies. Most comparisons we made would benefit from the availability of more studies involving more people with aphasia.
The evidence on which this review is based was up-to-date as of 1 July 2013. One small study carried out at a head and neck cancer clinic based at a university in the Netherlands was found. The study included 26 adults who had been treated for head and neck cancer either with radiotherapy or a combination of radiotherapy and surgery. All participants were missing all their teeth in the lower jaw and were experienced problems retaining a denture. The participants were split into two groups, 13 of them were treated with HBO and the other 13 were not. Only one small trial that was at high risk of bias compared treatment with HBO with treatment without HBO. The results failed to determine a benefit for HBO therapy in preventing failure of dental implants or other serious complications such as the death of bone in the jaw caused by radiotherapy treatment. More reliable studies are needed to provide the final answer to this question. The quality of evidence was very low as it was based on one small trial at high risk of bias.
The evidence is current to 26 March 2019. We found 52 studies with 41,331 participants. Six studies are awaiting classification (because we did not have sufficient information to assess them), and two studies are ongoing. All studies included people having surgery under general anaesthesia. Three studies included only people who were at high risk of intraoperative awareness, and two studies included only people who were not selected according to high risk of intraoperative awareness. Forty-eight studies compared BIS-guided anaesthesia with anaesthesia guided by clinical signs, and six studies compared BIS-guided anaesthesia with ETAG-guided anaesthesia. We found low-certainty evidence that BIS-guided anaesthesia may reduce the risk of intraoperative awareness. However, events were rare and only five of 27 studies reported incidences. When BIS-guided anaesthesia was used, we found three per 1000 fewer incidences of intraoperative awareness compared to nine per 1000 incidences when anaesthesia was guided by clinical signs. In addition, we found low-certainty evidence that BIS may improve recovery - the time for people to open their eyes was less, as was the time for orientation, and the time to be discharged from the post-anaesthesia care unit. We found no evidence of a difference in incidences of intraoperative awareness according to whether anaesthesia was guided by BIS or by ETAG, although, again, there were few incidences of awareness (1 per 1000 in each group). Only one study that compared BIS with ETAG-guided anaesthesia measured recovery times; this low-certainty evidence showed that discharge from the postanaesthesia care unit was earlier if anaesthesia was BIS-guided. No studies that compared BIS with ETAG-guided anaesthesia measured the time to eye opening or the time to orientation. We used GRADE to downgrade the evidence for all outcomes to low certainty. The incidence of intraoperative awareness is so rare and, even though we found some large studies, we concluded that the evidence was still imprecise. In addition, we judged many studies to have limitations because of high or unclear risks of bias. For example, all of the anaesthetists were aware of using an additional BIS monitor and we could not be certain how this affected the anaesthetists' standard practice. In addition, we noted that some studies did not report a clear definition of intraoperative awareness. Time points of measurement differed, and the methods used to identify intraoperative awareness also differed and we expected that some assessment tools were more comprehensive than others. Intraoperative awareness is rare, and despite finding a large number of eligible studies, evidence for the effectiveness of using BIS to guide anaesthetic depth is imprecise. We found low-certainty evidence that BIS-guided anaesthesia compared to anaesthesia guided by clinical signs may reduce the risk of intraoperative awareness and improve early recovery times in people having surgery under general anaesthesia. We found no evidence of a difference between BIS-guided anaesthesia and ETAG-guided anaesthesia, and we also judged this evidence to be low certainty.
This review sought to identify and review the randomised evidence comparing courses of chemotherapy containing antitumour antibiotics against courses not containing antitumour antibiotics. This review identified 34 eligible trials involving 5605 women. This review found that for women with advanced breast cancer, taking antitumour antibiotics did not result in better survival than women who took other types of chemotherapy drugs. Despite the lack of evidence of survival benefit, this review demonstrated that women taking these drugs had an advantage in time to progression (the length of time it takes for the cancer to progress after taking the drug) and tumour response (shrinking of the tumour) compared to women who did not take the antitumour antibiotic drugs. In addition however, the risks of side effects including cardiotoxicity, leukopenia and nausea/vomiting were all significantly increased in the women taking the antitumour antibiotics. Given that this review failed to show a benefit in survival for women taking this group of drugs but a higher rate of side effects, the use of these drugs in the management of metastatic breast cancer must be carefully weighed against the risk of these side effects.
We found one study with 186 participants (infants with cystic fibrosis up to two years of age) which was run across 40 centres in the USA. One infant (out of 92) who received palivizumab and one infant (out of 94) who received placebo were admitted to hospital due to infection from respiratory syncytial virus. No infants died. Overall, the number of adverse events in the palivizumab group was similar to that in the placebo group. No serious adverse events were reported to be related to the vaccine. Over the longer term (12 months), weight gain and the number of infections with Pseudomonas aeruginosa (a common bacterial infection in cystic fibrosis) were similar between groups. The limitation of all these findings is that we only identified one study. More research is needed on the use of the palivizumab vaccination in children with cystic fibrosis. We thought there was a low risk that it would be know which treatment group the next participant would be put into, although it was not clear how this order was generated. We also thought that participants and study personnel were sufficiently blinded to the treatment to avoid bias and that any missing data were unlikely to bias the study results. However, we did have concerns about bias from selective reporting (summary statements were presented but without any data) and the fact that this industry-supported study has not been published as a full report in a peer-reviewed journal.
This Cochrane Review is current to January 2019. We found nine trials with 1007 participants. Participants mean age was 56 to 68 years, and females comprised 29% to 56% of the participants. The participants had symptoms for several months or years and were diagnosed with a full-thickness tear with magnetic resonance imaging or ultrasound examination. Studies were conducted in Finland, Norway, Canada, USA, France, the Netherlands, Italy and South Korea. Our primary analysis included three trials with 339 participants who received either surgery (tendon repair and removal of bone from undersurface of acromion) or non-operative therapy (exercises with or without glucocorticoid injection). Three studies received funding however none of them reported using the funds directly for these trials. Compared with non-operative treatment, surgery resulted in little or no benefit in people with rotator cuff tears for up to one year. Pain (lower scores mean less pain) Improved by 9% (4% better to 13% better) or 0.9 points on a zero to 10 scale • People who had non-operative treatment rated their pain as 1.6 points • People who had surgery rated their pain as 0.7 points.  Function (0 to 100; higher scores mean better function)Improved by 6% (2% better to 10% better) or 6 points on a zero to 100 scale • People who had non-operative treatment scored 72 points • People who had surgery scored 78 points Participant-rate global treatment success (participants satisfied with the outcome) 7% more people rated their treatment a success (4% fewer to 13% more), or seven more people out of 100. • 48/55 (873/1000) of people considered treatment as successful with non-operative treatment • 51/54 (943/1000) of people considered treatment as successful with surgery Overall quality of life (higher scores mean better quality of life)Worsened 1% (4% worse to 2% better) or 1.3 points on a zero to 100 scale • People who had non-operative treatment rated their quality of life 58 • People who had surgery (subacromial decompression) rated their quality of life 57 Adverse events • One adverse event (frozen shoulder) was reported in the trials in exercise group. Thus, we are unable to estimate comparative risk. Serious adverse events • No serious adverse events were reported in the trials. As compared with non-operative treatment, moderate-certainty evidence (downgraded due to risk of bias) indicates that surgery (rotator cuff repair with or without subacromial decompression) probably provides little or no benefit in pain and low-certainty evidence indicates that it may provide little or no improvement in function, participant-rated global treatment success or overall quality of life (downgraded due to bias and imprecision) in people with rotator cuff tears. Due to only one reported adverse event across the trials, we cannot estimate if there is higher risk for adverse events after either treatment (very low-certainty evidence).
We identified six studies that compared cognitive rehabilitation with a control group who received their usual care (but not cognitive rehabilitation) for people with attention problems following stroke. We did not consider listening to music, meditation, yoga, or mindfulness to be a form of cognitive rehabilitation. The six studies involved 223 participants who demonstrated attentional problems or reported having such problems following stroke. The evidence is current to February 2019. We found no evidence that cognitive rehabilitation improved general (global) measures of attention. The group that received cognitive rehabilitation performed better than the control group on tasks that required people to divide attention. However, this benefit was only seen immediately after the rehabilitation period with no suggestion that the benefits persist for longer. There was no evidence to suggest that cognitive rehabilitation was beneficial for other types of attention problems, or daily life activities, mood, or quality of life. More research is needed. The very low to moderate methodological quality of the studies identified, and the lack of studies means that we cannot draw firm conclusions about the effect of cognitive rehabilitation for attention following stroke.
Nine studies of medium to high quality, enrolling 1614 institutionalised participants or outpatients, assigned to antibiotics or placebo/no treatment for treating asymptomatic bacteriuria for different durations of treatment and follow-up were included in this review. The evidence is current to February 2015. No clinical benefit was found for antibiotic treatment. Antibiotics eradicated the growth of bacteria in more participants but at the cost of more adverse events than in the no treatment groups.
To answer this question twelve studies of six to 14 months duration involving 350 people were analysed. Thyroid hormone therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity (for example less heart attacks or strokes). Data on health-related quality of life and symptoms did not demonstrate significant differences between placebo and thyroid hormone therapy. Some evidence indicated that thyroid hormone had some effects on blood lipids and technical measurements of heart function. Adverse effects were inadequately addressed in most of the included studies and have to be urgently investigated in future studies, especially in older patients.
The herb black cohosh was traditionally used by Native Americans to treat menstrual irregularity, with many experimental studies indicating a possible use for black cohosh in menopause. This review set out to evaluate the effectiveness of black cohosh for controlling the symptoms of menopause. The review of 16 studies (involving 2027 women) found insufficient evidence to support the use of black cohosh for menopausal symptoms. Given the uncertain quality of most studies included in the review, further research investigating the effectiveness of black cohosh for menopausal symptoms is warranted. Such trials need to give greater consideration to the use of other important outcomes (such as quality of life, bone health, night sweats and cost-effectiveness), stringent study design and the quality reporting of study methods.
Our search for eligible studies conducted on 31 January 2016 revealed five studies, all comparing cup and bottle feeding in newborn infants, which we were able to include in this review. These studies were conducted in neonatal and maternity units in hospitals in Australia, the United Kingdom, Brazil and Turkey. The mean gestational age of the infants in most of the studies were similar at the time of entry into the study. In four of the studies the intervention (cup or bottle) commenced from the time of enrolment into the study, when the infants first needed a supplemental feed and were as young as 30 weeks' gestation. In the study conducted in Turkey, supplemental feeding was not commenced on enrolment into the study and at the time of first supplemental feed but delayed until infants were at least 35 weeks of age. For some of the outcomes, the results of the different studies could not be combined. This included not breastfeeding at hospital discharge; not exclusively breastfeeding at three months and at six months; the average time taken for a feed; and the number of days spent in hospital. For each of these outcomes, the results from some studies favoured cup feeding, while the results from other studies favoured bottle feeding. For some of the outcomes, the results of the different studies could be combined: there was no difference in weight gain or gestational age at discharge between those infants who recieved supplemental feeds by cup compared to bottle. However those infants who received supplemental feeds by cup were more likely to be exclusively breastfeeding at hospital discharge and were more likely to be receiving some breastfeeds at three and six months of age. As the studies mostly included preterm infants and few term infants, no recommendations can be made for cup feeding term infants. The quality of evidence for weight gain, length of stay, not breastfeeding at hospital discharge and at six months of age and exclusively breastfeeding at hospital discharge and at six months of age is graded very low to low. In the studies included in this review, it is reported that many infants who were to receive supplemental feeds by cup received supplemental feeds by other means as either the parents or nurses did not like cup feeding.
All of the identified randomised clinical trials comparing emergency sclerotherapy with vasopressin (+/- intravenous or transdermal nitroglycerin), terlipressin, somatostatin, or octreotide have been reviewed. A total of 17 randomised trials including 1817 patients were included. Sclerotherapy did not appear to be superior to the vasoactive drugs in terms of control of bleeding, number of transfusions, 42-day rebleeding and mortality, or rebleeding and mortality before other elective treatments. However, adverse events were significantly more frequent and severe with sclerotherapy than with vasoactive drugs.
This review of three studies did not show any difference in effectiveness between sargramostim and placebo (fake drug) for induction of remission or clinical improvement in patients with active Crohn's disease. Side effects associated with sargramostim treatment included bone pain, musculoskeletal chest pain, and dyspnea (shortness of breath). Due to the fact that there were only a small number of trials in this area and some of them give opposite results, the authors concluded that while sargramostim does not appear to be more effective than placebo more research is needed to determine if this drug provides a benefit for the treatment of active Crohn's disease.
We looked at studies where people had general anaesthesia for surgery, and received larger or smaller amounts of intravenous fluid, and were later checked to see if they developed nausea and vomiting after their surgeries were done. We found 41 studies, with 4224 participants analysed in our review. Our review suggests that giving people extra intravenous fluid during surgery under general anaesthesia probably decreases the risk of having either nausea or vomiting after surgery, and probably reduces the need for medication to treat nausea. It is unclear how giving extra intravenous fluid affects the risk of unexpectedly needing hospital admission after minor surgery. No studies looked at whether extra intravenous fluid makes other complications worse. There are two reasons why the conclusions of this review may not be exactly correct. First, many of the studies were not designed perfectly. Second, the studies did not agree on exactly how helpful the extra intravenous fluids were for preventing nausea and vomiting. Most studies did find it at least somewhat helpful.
This review set out to assess any benefit or harm in using fish oil to reduce the risk of kidney damage and heart disease in people who have had a kidney transplant and are receiving standard drugs to prevent rejection. Information from 15 studies was used and showed that fish oils provide a slight improvement in HDL cholesterol and diastolic blood pressure. These studies did not provide enough information on the differences in the risk of death, heart disease, kidney transplant rejection or kidney function between patients receiving fish oils and those receiving placebo. There appeared to be no harmful effects of taking fish oil. The benefits of taking fish oil after a kidney transplant are a mild improvement in some heart disease risk factors. There was not enough information to show any benefit in preventing heart disease or reduction in kidney function. Larger, better studies are needed before regular use of fish oil can be recommended.
Nineteen studies fulfilled our predetermined criteria but only six could be combined (in meta-analysis). We obtained additional data from trialists. We were not able to combine results in children due to limited data. Thickened feeds had an inconsistent effect. Proton pump inhibitors (PPI) did not reduce cough and should not be used for cough in young children. In adults with cough and GORD, no significant difference was found in clinical cure using proton pump inhibitors (PPI) for cough and GORD. Using other outcomes, there was also no significant difference between PPI and placebo. This review also highlights a large placebo and time period effect (natural resolution with time) of treatment for chronic cough. In adults treatment with PPI for cough associated with GORD is inconsistent and its benefit variable. There was insufficient data to draw any conclusion from other therapies for cough associated with GORD.
This review looked at the benefits and harms of IgG, anti CMV vaccines and interferon to prevent CMV disease in solid organ transplant recipients. Thirty seven studies (2185 participants) were identified. This review shows that IgG did not reduce the risk of CMV disease or all-cause mortality compared with placebo or no treatment. The combination of IgG with antiviral medications (aciclovir or ganciclovir) were not more effective than antiviral medications alone in reducing the risk of CMV disease or all-cause mortality. Anti CMV vaccines and interferon did not reduce the risk of CMV disease compared with placebo or no treatment. Currently there are no indications for IgG in the prevention of CMV disease in recipients of solid organ transplants.
We searched databases in August 2013 for randomised controlled trials (clinical trials where people are randomly allocated to one of two or more treatment groups) conducted in adults (aged 18 years or over) who did not have gastric cancer at the start of the trial. Treatment had to be with PPI for six months or more and be compared with no treatment, surgery/endoscopic treatment (where a tube is passed down the food pipe and into the stomach), or any other antacid treatment. We found seven randomised controlled trials with 1789 participants. Some trials only partially reported gastric pre-cancerous lesions, and there was a substantial proportion of participants with missing data. We concluded that there was no clear evidence to support the notion that the long-term use of PPIs could promote the development of pre-cancerous lesions. However, there was a potentially elevated risk of developing a thickening of the stomach lining (hyperplasia) among participants with long-term PPI use, which is considered as a possible pre-condition of gastric carcinoid (a relatively benign (non-cancerous) tumour that develops within the stomach lining). Currently, available evidence was of low or very low quality, due to their study design and the large proportion of missing data. We therefore suggest future well-designed clinical trials should be performed for providing better understandings regarding this question.
This review investigated whether this intervention is safe and whether it is more effective than the traditional treatment. In order to answer this question, 4 randomised trials were found, comparing these two interventions. We found that ERAS can be viewed as safe, i.e. not resulting in more complications or deaths, and at the same time decreases the days spent in hospital following major bowel surgery. However, the data are of low quality and therefore does not justify implementation of ERAS as the standard method of care yet. More research on other outcome parameters like economical evaluation and quality of life parameters are necessary.
The objective of this review was to evaluate the benefits and harms of phyllanthus species for patients with chronic HBV infection. Phyllanthus species appear to be safe and may potentially have effects on the clearance of viral markers in patients with HBV infection. However, all of the trials evaluated in this review were of low methodology quality, ie, have high risk of bias, and there was a risk of random errors in the majority of comparisons. Furthermore, all analyses showed substantial heterogeneity. Accordingly, randomised clinical trials with low risk of bias and large sample size should be conducted to confirm the effects of phyllanthus species before clinical use is considered.
One of these drugs is bevacizumab (Avastin) which has been studied in clinical trials in metastatic breast cancer. Trials with other drugs are ongoing. Data are available from seven randomised trials, which evaluated the effect of bevacizumab on the primary endpoint in a total of 4032 patients with metastatic breast cancer. These patients were either-hormone receptor negative or had progressed on hormonal treatment. The primary end point was progression-free survival and secondary end points included overall survival, response rate measuring the change in size of the tumour, quality of life and toxicity of the treatment. Progression-free survival is considered a surrogate end point, i.e. a substitute for overall survival as an end point. The addition of bevacizumab to chemotherapy significantly prolongs progression-free survival and response rates in patients who have had previous chemotherapy and those who have not had previous chemotherapy for metastatic disease. The magnitude of this benefit is dependent on the type of chemotherapy used. Best results have been observed for the combination of weekly paclitaxel and bevacizumab in patients without prior chemotherapy for metastatic disease. Although progression-free survival was significantly longer with bevacizumab, there was no significant effect observed on either overall survival or quality of life. Quality of life is a direct measure of benefit to the patient. Adverse effects of bevacizumab in breast cancer are generally manageable, but may be serious and include increased frequencies of high blood pressure, blood clots in arteries and bowel perforations. However, overall rates of treatment-related deaths were lower in patients treated with bevacizumab. Because of the lack of effect on overall survival and quality of life, it is regarded as controversial whether bevacizumab is associated with a true patient benefit in spite of the increase in progression-free survival.
We included eight randomized controlled trials in the review, and we based our analysis on seven of these: two cross-over trials that included 125 participants, and five parallel trials involving 492 participants. The mean age of participants varied from 71.5 years to 83.5 years. Oral sedation was used for two trials only. No trial used oral analgesics before the operation, and no trials mentioned their source of funding. This review showed that sub-Tenon’s anaesthesia provided slightly better pain relief than topical anaesthesia during cataract surgery. The difference was equal to 1.1 on a scale from 0 to 10. Pain on the day after surgery was slightly lower for participants who received topical anaesthesia, and the difference was equivalent to 0.2 on a scale from 0 to 10. Both surgeons and participants preferred sub-Tenon’s anaesthesia. However, all trials were performed at a time when surgeons were only starting to use topical anaesthesia. There was not enough evidence from included trials to say whether one anaesthetic technique would be associated with a lower or higher incidence of important surgical complications during surgery (posterior capsular tear, iris prolapse) that may lead to postoperative complications and eventually to poorer vision. Topical anaesthesia and sub-Tenon’s anaesthesia therefore are accepted and safe methods of providing anaesthesia for cataract surgery.
There was moderate quality evidence from one study which showed that pregnant women who received supportive, informative text messages experienced higher satisfaction and confidence, and lower anxiety levels in the antenatal period than women who did not receive these. There was low quality evidence that there was no difference in pregnancy outcomes. We found one trial that provided high quality evidence that regular support messages sent by text message can help people to quit smoking, at least in the short-term. One study assessing whether mobile phone messaging promoted use of preventive medication reported moderate quality evidence of higher self-reported adherence by people receiving the messages. A fourth study on healthy behaviours in children found very low quality evidence showing that the interventions had no effect. There was very low quality evidence from one study that people's evaluation of the intervention was similar between groups. There was moderate quality evidence from one study of no difference in harms of the intervention, measured as rates of pain in the thumb or finger joints, and car crash rates. There were no studies reporting outcomes related to health service utilisation or costs. Although we find that, overall, mobile phone messaging can be helpful for some aspects of preventive health care, much is not yet known about the long-term effects or potential negative consequences.
This review aimed to compare the effectiveness and complications between ESWL and stones removing using the nephroscopy through the skin at kidney level (PCNL) or ureteroscope through the bladder and ureter to the kidney (RIRS). Five small randomised studies (338 patients) were included. Four studies compared ESWL with PCNL and one study compared ESWL with RIRS. Patients with kidney stones who undergo PCNL have a higher success rate than ESWL whereas RIRS was not significantly different from ESWL. However, ESWL patients spent less time in hospital, duration of treatment was shorter and there were fewer complications.
We found 20 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) comparing diet, physical activity and behavioural (where habits are changed or improved) treatments (interventions) to a variety of control groups (who did not receive treatment) delivered to parents only of 3057 children aged 5 to 11 years. There were few similarities between the trials in the nature and types of interventions used. We grouped the trials by the type of comparisons. Our systematic review reported on the effects of the parent-only interventions compared with parent and child interventions, waiting list controls (where the intervention was delayed until the end of the trial), other interventions with only minimal information or contact and other types of parent-only interventions. The children in the included trials were monitored (called follow-up) for between six months and two years. This evidence is up to date as of March 2015. The most reported outcome was the body mass index (BMI). This is a measure of body fat and is calculated by dividing weight (in kilograms) by the square of the body height measured in metres (kg/m2). The studies measured BMI in ways that took account of gender, weight and height as the children grew older (such as the BMI z score and the BMI percentile). When compared with a waiting list control, there was limited evidence that parental interventions helped to reduce BMI. In looking at the longest follow-up periods of the included trials, we did not find firm evidence of an advantage or disadvantage of parent-only interventions when compared with either parent and child interventions, or when compared with limited information. Our review found very little information about how different types of parental interventions compared. No trial reported on death from any cause, illness or socioeconomic effects (such as whether parent-only interventions are lower in costs compared with parent and child interventions). Two trials reported no serious side effects and the rest of the trials did not report whether side effects occurred or not. Information on parent-child relationships and health-related quality of life was rarely reported. The overall quality of the evidence was low, mainly because there were just a few trials per measurement or the number of the included children was small. In addition, many children left the trials before they had finished.
We found 15 studies that assessed the effect of diaphragm-triggered non-invasive respiratory support in infants through searches of medical databases up to 10 May 2019. Of these 15, two studies (involving a total of 23 preterm infants) were eligible for inclusion in the review. Ten studies were either awaiting publication or are ongoing. There is limited data from randomised controlled trials to determine the effect of diaphragm-triggered non-invasive respiratory support on important outcomes. We were able to include only two small randomised controlled trials in the review. Both studies involved infants switching from one type of support to the other and were focused on short-term changes in breathing patterns. We were not able to make any meaningful conclusions in this review due to limited data and very low quality evidence. Large, high-quality studies are needed to determine whether diaphragm-triggered non-invasive respiratory support can prevent respiratory failure.
We found nine studies with 727 participants testing antipsychotics for delirium treatment; four trials compared an antipsychotic to another drug class or placebo and seven of the nine trials compared a typical antipsychotic to an atypical antipsychotic. We found no evidence to support or refute the suggestion that antipsychotics shorten the course of delirium in hospitalised patients. Based on the available studies, antipsychotics do not reduce the severity of delirium or resolve symptoms compared to nonantipsychotic drugs or placebo or lower the risk of dying. We found no evidence to support or refute the suggestion that antipsychotics shorten hospital length of stay or improve health-related quality of life. Side effects were rarely reported in the studies. It is important to note many clinically relevant outcomes were not reported in the studies and the overall quality of the available evidence was poor. Canadian Fraility Network (previously Technology Evaluation in the Elderly Network [TVN]) (www.cfn-nce.ca/), Canada
The evidence is current to May 2014. We found 27 trials (with a total of 2485 participants) examining whether exercise can help reduce neck pain and disability; improve function, global perceived effect, patient satisfaction and/or quality of life. In these trials, exercise was compared to either a placebo treatment, or no treatment (waiting list), or exercise combined with another intervention was compared with that same intervention (which could include manipulation, education/advice, acupuncture, massage, heat or medications). Twenty-four of 27 trials evaluating neck pain reported on the duration of the disorder: 1 acute; 1 acute to chronic; 1 subacute; 4 subacute/chronic; and 16 chronic. One study reported on neck disorder with acute radiculopathy; two trials investigated subacute to chronic cervicogenic headache. Results showed that exercise is safe, with temporary and benign side effects, although more than half of the trials did not report on adverse effects. An exercise classification system was used to ensure similarity between protocols when looking at the effects of different types of exercises. Some types of exercise did show an advantage over the other comparison groups. There appears to be a role for strengthening exercises in the treatment of chronic neck pain, cervicogenic headache and cervical radiculopathy if these exercises are focused on the neck, shoulder and shoulder blade region. Furthermore, the use of strengthening exercises, combined with endurance or stretching exercises has also been shown to be beneficial. There is some evidence to suggest the beneficial effects of specific exercises (e.g. sustained natural apophyseal glides) with cervicogenic headaches and mindfulness exercises (e.g. Qigong) for chronic mechanical neck pain. There appears to be minimal effect on neck pain and function when only stretching or endurance type exercises are used for the neck, shoulder and shoulder blade region. No high quality evidence was found, indicating that there is still uncertainty about the effectiveness of exercise for neck pain. Future research is likely to have an important impact on the effect estimate.There were a number of challenges with this review; for example, the number of participants in most trials was small, more than half of the included studies were either of low or very low quality and there was limited evidence on optimum dosage requirements.
We identified 20 randomised controlled trials (studies in which participants are assigned to a treatment group using a random method) (2853 analytic units consisting of 1681 individual patients and 1172 individual legs) in our most recent search on 12 June 2018. Nine trials compared wearing stockings to no stockings, and 11 compared stockings plus another method with that method alone. The other methods used were dextran 70, aspirin, heparin, and mechanical sequential compression. Of the 20 trials, 10 included patients undergoing general surgery; six included patients undergoing orthopaedic surgery; three individual trials included patients undergoing neurosurgery, cardiac surgery, and gynaecological surgery, respectively; and only one trial included medical patients (patients who were admitted to the hospital for reasons other than surgery). The compression stockings were applied on the day before surgery or on the day of surgery and were worn up until discharge or until the patients were fully mobile. Thigh-length stockings were used in the vast majority of included studies. The included studies were of good quality overall. We found that wearing GCS reduced the overall risk of developing DVT, and probably also DVT in the thighs. We found that GCS may also reduce the risk of PE amongst patients undergoing surgery. As only one trial included medical patients, results for this population are limited. The occurrence of problems associated with wearing GCS was poorly reported in the included studies. Our review confirmed that GCS are effective in reducing the risk of DVT in hospitalised surgical patients (high-quality evidence). It also demonstrated that GCS probably reduce the risk of developing DVT in the thighs (proximal DVT, moderate-quality evidence) and PE (low-quality evidence). Reasons for downgrading the quality of the evidence included low event rate (i.e. small number of participants who developed DVT) and uncertainty due to only a small number of patients being routinely screened for proximal DVT or PE. Limited evidence was available for hospitalised medical patients, with only one study suggesting that GCS may prevent DVT in such patients.
This review looked at the evidence from 26 clinical trials with a total of 2736 adult cancer patients. Many of the trials were small and of moderate quality. Only three studies were less than 10 years old. Thymosin α1 is a synthetic peptide that shows some promise as a treatment option for patients with metastatic melanoma when used in addition to chemotherapy. Severe problems occur during chemotherapy and radiotherapy due to low white blood cell counts and infections. These were reduced by using purified thymus extracts. However, the use of purified thymus extracts should be investigated more thoroughly before the extracts are used routinely in patients. The findings were not conclusive and caution is advised. Overall, thymic peptides seem to be well tolerated.
This review included six trials and investigated the efficacy and tolerability of risperidone, an atypical antipsychotic, as treatment for mania compared to placebo or other medicines. High withdrawal rates from the trials limit the confidence that can be placed on the results. Risperidone, both as monotherapy and combined with lithium, or an anticonvulsant, was more effective at reducing manic symptoms than placebo but caused more weight gain, sedation and elevation of prolactin levels. The efficacy of risperidone was comparable to that of haloperidol both as monotherapy and as adjunctive treatments to lithium, or an anticonvulsant. Risperidone caused less movement disorders than haloperidol but there was some evidence for greater weight gain.
We included three studies from the 2013 review and an additional five new studies from the current review, for a total of eight studies with 450 participants (180 women). The number of participants in the included studies ranged between 17 and 131; the mean age of participants was between 63 and 71 years. Six studies explored the effects of combined aerobic and strengthening exercises; one explored the effects of combined aerobic exercise and inspiratory muscle training; and one explored the effects of combined aerobic exercise, strengthening exercise inspiratory muscle training and balance training. The length of the exercise programmes ranged from four to 20 weeks, with exercises performed twice to five days a week. Our results showed that people with NSCLC who exercised after lung surgery had better fitness level (measured using both a cycling test and the six-minute walk test) and strength in their leg muscles compared to those that did not exercise. We also showed initial evidence for better quality of life and less breathlessness in those who exercised. One adverse event (hip fracture) related to the intervention was reported in one study. The effect of exercise training after lung surgery on grip strength, fatigue, and lung function was uncertain. We found insufficient evidence for improvements in the strength of breathing muscles or feelings of anxiety and depression. Overall the quality (certainty) of evidence for the outcomes was moderate, ranging between very low (for breathlessness) and high (for fitness level measured via the six-minute walk test).
Ten studies (994 participants) provided information for the review. These ten studies compared outpatient antibiotic therapy (491 participants) versus inpatient therapy (503 participants) in people with cancer who developed febrile neutropaenia. Six studies were conducted in adults (628 participants) and four studies were in children (366 participants). These ten trials compared effectiveness in terms of the disappearance of signs of infection (mainly fever) and nine studies assessed the effect on mortality (death). Eight studies recorded the number of treatment days for the fever to resolve. Five studies compared the duration of neutropaenia between out- and inpatients. Five studies analysed duration of antibiotics usage and six looked at the duration of hospitalisation.Two studies assessed quality of life for patients. In eight of the 10 studies, outpatient antibiotic therapy was part of an early discharge programme, i.e. antibiotics were given for a few days in the hospital and then the participants was discharged home. In the other two studies, the antibiotics were started at home. Outpatient antibiotic therapy is probably as effective as inpatient therapy in people (both in adults and children) with cancer who develop febrile neutropaenia for improving the signs of infection, including reducing fever. There was probably little or no difference in mortality between the outpatient therapy and inpatient therapy, as well as in the duration of treatment with antibiotics, or frequency of adverse events related to the use of antibiotics. Treatment as an outpatient may reduce the number of days patients need to be treated in hospital. In general, the studies were of moderate certainty.
a total of 11 studies were identified with 1296 women; most studies were conducted in the USA. Four studies evaluated the use of antibiotics before the birth (antepartum); six studies evaluated the use of antibiotics after birth (postpartum); and one compared antibiotic administration both before and after birth. the quality of the evidence was ranked low to very low, mainly because many studies had methodological limitations with outcome results based on limited numbers of trials and included participants that could be pooled. based on the findings of one study, treatment during labor was found to be more effective than treatment after labor; however this finding relates only to maternal and neonatal length of hospital stay and to neonatal severe infection. No evidence indicated that a higher dose of antibiotics before birth was superior to a lower dose. Immediately following birth, no evidence showed that different types of antibiotics or longer or shorter treatment duration improved the health of the mother and her newborn. All women who participated in the postpartum trials received antibiotics before the time of birth. Therefore insufficient information was available from randomized controlled trials to reveal the most appropriate regimen of antibiotics for the treatment of patients with intra-amniotic infection, whether antibiotics should be continued during the postpartum period, and which antibiotic regimen should be used and for what duration. None of the included studies reported information related to adverse effects of the intervention.
This review of 49 trials found that treating children with a short course (less than seven days) of antibiotics, compared to treatment with a long course (seven days or greater) of antibiotics, increases the likelihood of treatment failure in the short term. No differences are seen one month later. The amount of gastrointestinal adverse events decreased with a shorter course of antibiotics.
We found eight randomised controlled trials (RCTs), which investigated four different types of vitamin or mineral pills by comparing them to a placebo (a dummy pill). The vitamins tested were B vitamins (vitamin B6, vitamin B12 and folic acid), vitamin E, and vitamin E and C given together. The only mineral tested was chromium. Vitamin B combination versus placebo Five trials with a total of 879 participants compared B vitamins with placebo. Four used combinations of vitamin B6, vitamin B12, and folic acid; one small study tested folic acid on its own. None of these studies reported whether or not participants developed dementia. These studies did not find that memory or thinking skills differed between the group of people who took vitamin B supplements and those who took placebo after treatment lasting six months to two years. Our confidence in the results on different tests used in the studies varied from moderate to very low. Two years of vitamin B supplements did seem to help memory in a small subgroup of participants in one study who could be identified by a particular blood test at the start of the trial. One study found that there was probably no effect on participants' quality of life. One study scanned the brains of some participants and reported that B vitamins may slow the rate of brain shrinkage. Harmful effects and deaths were reported in very few participants and we cannot conclude whether or not there are harms from taking these or similar combinations of B vitamins. Vitamin E versus placebo. One study with 516 participants compared a relatively high dose of vitamin E (2000 IU a day) to placebo in people who were also taking a multivitamin containing 15 IU of vitamin E (the daily requirement for vitamin E is approximately 30 IU). The risk of developing dementia due to Alzheimer’s disease (the commonest form of dementia) is probably not affected by three years of treatment with high-dose vitamin E. The quality of the evidence for other outcomes was lower, but there may also be no effect of this dose of vitamin E on specific memory or thinking skills or on how well people could manage their daily activities. Vitamin E and C versus placebo One study with 256 participants compared a combination of vitamins C and E with placebo. It found no effect on overall memory and thinking skills, but we had little confidence in this result because of the quality of the evidence. Chromium picolinate versus placebo Only one very small study with 26 participants investigated the effect of chromium supplements. This study was too small for us to be able to draw any conclusions. The amount and quality of research evidence about vitamin and mineral supplements for treating MCI in people without nutritional deficiency is limited. At the moment, it is not possible to identify any supplements which can reduce the risk of people with MCI developing dementia or which can effectively treat their symptoms. More research is needed before we can answer our review question.
The review found that there is insufficient evidence from studies to show that such changes reduce the number of injuries in the home but does not conclude that these interventions are ineffective. Home alterations need to be evaluated by larger and better designed studies which include injuries in their outcomes.
This review included 29 studies involving 23019 participants. When we compared the effects of dipyridamole (alone or together with aspirin) with aspirin alone there was no evidence of an effect on death from vascular causes. When we compared the effects on the occurrence of vascular events (strokes, heart attacks, and deaths from vascular diseases) the combination of aspirin and dipyridamole had an advantage over aspirin alone. This result holds particularly true for patients with ischaemic stroke.
This review examines the effects of different surgical techniques. It found insufficient evidence from randomised trials to assess the effects of compression or of impaction of the fracture during surgery. It found limited evidence that open reduction (surgically exposed) as compared with closed reduction (under X-ray control) resulted in a greater length of surgery. The lack of evidence showing benefit of open reduction supports the use of closed reduction of these fractures.
This review compared any type of respiratory muscle training with standard care or sham treatments. We reviewed 11 studies (including 212 people with cervical spinal cord injury) and suggested that for people with cervical spinal cord injury there is a small beneficial effect of respiratory muscle training on lung volume and on the strength of the muscles used to take a breath in and to breathe air out and cough. No effect was seen on the maximum amount of air that can be pushed out in one breath, or shortness of breath. An insufficient number of studies had examined the effect of respiratory muscle training on the frequency of lung infections or quality of life, so we could not assess these outcomes in the review. We identified no adverse effects of training the breathing muscles for people with a cervical spinal cord injury.
The review included three studies with 524 people with sickle cell disease aged between 12 and 65 years of age. The intervention in one study was zinc sulphate and in two studies was senicapoc. Each study was compared to a placebo group (a substance which contains no medication). For each study people were selected for one treatment or the other randomly. The studies lasted from three months to 18 months. The study with zinc sulphate showed that this drug may be able to reduce the number of sickle cell crises without causing toxic effects (low-quality evidence). There were 145 participants in this study and results showed a significant reduction in the total number of serious sickle-related crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (moderate-quality evidence). However, our analysis was limited since not all data were reported. Changes to red blood cell measurements and blood counts were not consistent (very low-quality evidence). No serious adverse events were noted in the study. The two studies with senicapoc demonstrated that this drug increases the red blood survival and has a role in preventing red blood cell dehydration in people with sickle cell disease (very low-quality evidence). The higher dose of the drug was more effective compared to the lower dose. But these changes in the red blood cells did not translate into positive clinical outcomes in terms of reduction in the number of sickle cell crises (low-quality evidence). Senicapoc had a favourable safety profile. More longer-term research is needed on these drugs and others that might prevent water loss in red blood cells. Given this is no longer an active area of research, this review will no longer be regularly updated. The quality of the evidence was mixed across outcomes.
Systematic review of 86 randomised clinical trials including 10,716 patients and statistical analyses of the data showed that coronary artery bypass surgery performed on the beating heart results in an increased risk of death. No firm evidence for benefit or harm was found regarding the outcome measures myocardial infarction, stroke, atrial fibrillation, renal insufficiency, or coronary reintervention. Our data raises a warning regarding coronary artery bypass surgery on the beating heart and cardiac arrest and cardiopulmonary bypass seem less risky. In patients with contraindications for cannulation of the aorta and cardiopulmonary bypass coronary artery bypass surgery on the beating heart may be a solution but we need randomised clinical trials in these patients to identify the most beneficial approach.
We searched for articles from different sources including published research papers, unpublished reports, and through direct communication with experts and organisations working to address iodine and micronutrient deficiency. We last searched the databases in January 2018. Eleven studies, which captured data on 4317 participants (3636 children, 648 women of reproductive age, and 33 infants), met our inclusion criteria. The type of foods used as vehicle to deliver iodine differed between the studies, and included biscuits, milk, fish sauce, drinking water, yoghourt, fruit beverage, seasoning powder, and infant formula milk. The amount of iodine provided to participants ranged from 35 µg/day to 220 µg/day, and study duration ranged from 11 days to 48 weeks. Of the 11 studies included, five examined the effect of adding iodine alone to foods compared to either no intervention or the same foods without iodine; while six evaluated the effect of adding iodine plus other micronutrients to foods compared to the same foods without iodine, but with different levels of other micronutrients. No study evaluated the effect of adding iodine to foods on death, mental development, cognitive function, cretinism (a condition characterized by impaired control of physical movement and intellectual disability), hypothyroidism (underactive thyroid), thyroid-stimulating hormone concentration, or serum thyroglobulin concentration (these are biological markers that indicate the presence of iodine deficiency when concentration in the blood is high). Two studies reported on the effect of the intervention on goitre, one study assessed five physical development measures (weight, height, weight-for-age, height-for-age, and weight-for-height scores), and one examined adverse effects. All studies assessed urinary iodine concentration (the concentration of iodine secreted in the urine, which indicates the presence of iodine deficiency when concentration is low in a population group, rather than in an individual). We combined the data that met our requirements in these studies in a meta-analysis. We are uncertain of the effects of iodine fortification on the proportion of participants with goitre, or on any of the five physical development measures. One study reported narratively that no adverse effects were observed during the trial. We found a significant increase of 38.32 µg/L in urinary iodine concentration after adding iodine to foods, compared to the groups that did not have iodine added, from studies of higher quality. Using GRADE, we rated the quality of the evidence as very low for goitre and physical development measures, due to study limitations (risk of bias) and imprecise results, and low for adverse events due to indirectness and imprecise results. We rated the quality of the evidence for urinary iodine concentration, from studies in which participants were allocated to treatment groups at random (gold standard design for clinical research), as moderate. On the other hand, quality of the evidence for urinary iodine concentration from studies without this random element was rated as very low, due to study limitations and imprecise results. Overall, there is no clear evidence on the effect of the intervention on reducing the proportion of people with goitre, improving physical growth, or adverse events. However, our results show that adding iodine to foods likely increases urinary iodine concentration. Additional studies to better quantify the effect of the intervention on these outcomes, as well as other outcomes, are needed.
This review identified three small studies (68 participants) comparing: 1) intravenous plus oral steroid treatment versus oral sterids; 2) oral versus short-course intravenous steroid treatment; and 3) oral steroid treatment versus placebo. Only oral steroid treatment (compared to short-course intravenous steroid treatment) showed an increase in the number of patients who achieved complete remission. However, the lack of available studies leaves important treatment questions unanswered; what is the optimal dose and duration of steroid treatment in new-onset adult minimal change disease; how are relapses following steroid-induced remission prevented and treated; and what are the appropriate treatments for steroid-dependent or treatment-resistant minimal change disease?
While there is a great deal of information on the causes of NBD, there are few studies that focus on how to practically manage the problem. Currently the usual advice is to have a good fluid intake, a balanced diet, as much physical exercise as is practical and a regular planned bowel routine. A bowel routine may include use of oral laxative medicines, suppositories or enemas; abdominal massage; digital rectal stimulation and digital evacuation of stool. The steps used will depend on the needs of each individual and some degree of trial and error is usually needed to achieve a satisfactory routine. Only research studies where participants were allocated to either the control group (who received either no intervention or usual care) or the treatment group by chance (called randomisation) were included in this review as these studies provide the most reliable evidence. Fifteen new studies have been added in this update. Five have been removed because the drugs the studies reported on (cisapride and tegaserod) have been withdrawn from the market and are no longer available. Most of the 20 randomised studies in this review included very small numbers of participants and the study reports did not always give the information needed to be sure that the study findings were reliable. Some oral laxatives were found to improve bowel function including psyllium, a stool-bulking laxative (one study), and an isosmotic macrogol (one study), which were both studied in individuals with Parkinson's disease. Some suppositories and micro-enemas used to help the bowel to open produced faster results than others (three studies) and the timing of suppository use may affect the response of the bowel (one study). Digital evacuation of stool may be more effective than oral or rectal medication (one study). The use of transanal irrigation in individuals with spinal cord injury improved bowel control, constipation and quality of life measures (one study). Three studies found that abdominal massage was helpful in reducing constipation. One study found that patients may benefit from even one educational contact with a nurse. This review shows that there is still remarkably little research on this common problem which is so important to patients. The research evidence found by the review is generally very poor because the way the studies were carried out and reported means that the results are not reliable. It is not possible to make recommendations for care based on these studies. Managing NBD will continue to rely on trial and error until more high quality studies with larger numbers of participants and which examine the most important aspects of this problem are carried out.
The evidence is current to May 2014. This review includes 23 randomised controlled trials with a total of 1309 participants whose chronic low back pain was evaluated with nerve blocks or other diagnostic tests. Both men and women, with a mean age of 50.6 years, were included. Patients with a positive response to a diagnostic block or to discography were given radiofrequency denervation, a placebo or a comparison treatment. No high-quality evidence shows that radiofrequency denervation provides pain relief for patients with chronic low back pain. Similarly, no convincing evidence suggests that this treatment improves function. Moderate-quality evidence suggests that radiofrequency denervation might better relieve facet joint pain and improve function over the short term when compared with placebo. Evidence of very low to low quality shows that radiofrequency denervation might relieve facet joint pain as well as steroid injections. For patients with disc pain, only small long-term effects on pain relief and improved function are shown. For patients with SI joint pain, radiofrequency denervation had no effect over the short term and a smaller effect (based on one study) one to six months after treatment when compared with placebo. For low back pain suspected to arise from other sources, the results were inconclusive. Radiofrequency denervation is an invasive procedure that can cause a variety of complications. The studies in this review were not of adequate quality and size to document how often complications occur. Given the poor quality of the evidence, large, high-quality studies are urgently needed to determine whether radiofrequency denervation is safe and effective.
We searched published and unpublished studies up to January 2017. We found 33 clinical trials with a total of 4477 participants; most were published in the 1980s and 1990s and were carried out in European countries. Eleven out of 33 studies received funding from pharmaceutical companies. Most studies included patients over 60 years old who had severe blocking of arteries of the leg; many also had diabetes. Follow-up was usually less than 1 year. We found that, when compared with placebo, prostanoids provided a small beneficial effect by alleviating pain in the leg at rest and improving ulcer healing. Prostanoids did not reduce deaths or the need for an amputation. We found that no studies evaluated the quality of life of people with this condition. We found insufficient evidence to compare effects of prostanoids against those of other medications or other prostanoids. Our findings suggest that taking prostanoids does cause harm. When 1000 patients are treated with prostanoids, on average 674 (572 to 798) will experience adverse events, compared with 319 given placebo. Adverse events usually include nausea, vomiting, diarrhoea, headache, dizziness, and flushing. More severe adverse events include low blood pressure, chest pain, and abnormalities in heart rhythm. When evaluating effects of prostanoids on rest-pain, ulcer healing, and adverse events, researchers provided moderate-quality evidence; review authors downgraded this in most cases because of loss of participants to follow-up. Evaluating cardiovascular mortality yielded evidence of low quality related to loss of participants to follow-up and small numbers of reported events. On the other hand, the quality of evidence on risk of amputation was high.
We searched for evidence up to 30 November 2016. This review now includes data from 30 randomised controlled trials involving 9015 pregnant women who gave birth without epidural anaesthesia. Overall, evidence was not of good quality. When women gave birth in an upright position, as compared with lying on their backs, the length of time they were pushing (second stage of labour) was reduced by around six minutes (19 trials, 5811 women; very low-quality evidence). Fewer women had an assisted delivery, for example with forceps (21 trials, 6481 women; moderate-quality evidence). The number of women having a caesarean section did not differ (16 trials, 5439 women; low-quality evidence). Fewer women had an episiotomy (a surgical cut to the perineum to enlarge the opening for the baby to pass through) although there was a tendency for more women to have perineal tears (low-quality evidence). There was no difference in number of women with serious perineal tears (6 trials, 1840 women; very low-quality evidence) between those giving birth upright or supine. Women were more likely to have a blood loss of 500 mL or more (15 trials, 5615 women; moderate-quality evidence) in the upright position but this may be associated with more accurate ways of measuring the blood loss. Fewer babies had problems with fast or irregular heart beats that indicate distress (2 trials, 617 women) when women gave birth in an upright position although the number of admissions to the neonatal unit was no different (4 trials, 2565 infants; low-quality evidence). This review found that there could be benefits for women who choose to give birth in an upright position. The length of time they had to push may be reduced but the effect was very small and these women might lose more blood. The results should be interpreted with caution because of poorly conducted studies, variations between trials and in how the findings were analysed. More research into the benefits and risks of different birthing positions would help us to say with greater certainty which birth position is best for most women and their babies. Overall, women should be encouraged to give birth in whatever position they find comfortable.
In this review, we included 13 trials that compared a combination of pelvic floor muscle training and another active treatment in 585 women with the same active treatment alone in 579 women to treat all types of urine leakage. There was not enough evidence to say whether or not the addition of pelvic floor muscle training to another active treatment would result in more reports of a cure or improvement in urine leakage and better quality of life, when compared to the same active treatment alone. There was also insufficient evidence to evaluate the adverse events associated with the addition of PFMT to other active treatment as none of the included trials reported data on adverse events associated with the PFMT regimen. Most of the comparisons were investigated by single trials, which were small. None of the trials included in this systematic review were large enough to answer the questions they were designed to answer. The quality of the evidence was rated as either low or very low for the outcomes of interest. The main limitations of the evidence were poor reporting of study methods, and lack of precision in the findings for the outcome measures.
In this review 22 studies were included. These studies randomised 2883 patients with type 1 diabetes to receive a form of CGM or to use self measurement of blood glucose (SMBG) using fingerprick. The duration of follow-up varied between 3 and 18 months; most studies reported results for six months of CGM use. This review shows that CGM helps in lowering the glycosylated haemoglobin A1c (HbA1c) value (a measure of glycaemic control). In most studies the HbA1c value decreased (denoting improvement of glycaemic control) in both the CGM and the SMBG users, but more in the CGM group. The difference in change in HbA1c levels between the groups was on average 0.7% for patients starting on an insulin pump with integrated CGM and 0.2% for patients starting with CGM alone. The most important adverse events, severe hypoglycaemia and ketoacidosis did not occur frequently in the studies, and absolute numbers were low (9% of the patients, measured over six months). Diabetes complications, death from any cause and costs were not measured. There are no data on pregnant women with diabetes type 1 and patients with diabetes who are not aware of hypoglycaemia.
This review investigated whether giving misoprostol to women after birth to prevent or treat excessive bleeding reduces maternal deaths and severe complications other than blood loss (which is covered in separate reviews). We included 78 randomised controlled studies involving 59,216 women. The variety of study designs, populations studied, routes of administration and co-interventions, as well as the exceptionally high incidence of hyperpyrexia in Ecuador were limiting factors. Maternal deaths, and the combined outcome, death or severe illness resulting in major surgery, admission to intensive care or vital organ failure (excluding very high fever) were not reduced by misoprostol. The known side effects of misoprostol (fever and very high fever) were worse with dosages of 600 µg or more than with lower dosages. Therefore, the review supports the use of the lowest effective misoprostol dose to prevent or treat maternal bleeding after the birth of the baby, and calls for more research to find out the optimal dosage, with continued surveillance for serious side effects.
We identified six studies up to August 2013, for inclusion in the review. These studies included a total of 1270 participants. Three of the trials compared routine shunting with no shunting, one trial compared routine shunting versus selective shunting, and another two trials compared different methods of monitoring in selective shunting. We have not yet identified any trials that compared selective shunting with no shunting. All the included trials assessed the use of shunting in people undergoing endarterectomy under general anaesthetic. The age of the participants ranged from 40 to 89 years, and overall, there were more male than female participants. Where reported, participants were followed up for no longer than 30 days. There is still no evidence for the use of a carotid shunt during carotid endarterectomy. This review suggests a benefit from the use of a shunt, but the overall results were not statistically significant. More trials are needed. There were significant problems with the quality of the randomised trials and, overall, the reporting of study methodology was poor.
This review investigated the effectiveness of personal assistance versus any other form of care for older adults (65+). An exhaustive literature search identified 4 studies that met the inclusion criteria, which included 1642 participants. They suggested that personal assistance may be preferred over other services; however, some people prefer other models of care. This review indicates that personal assistance probably has some benefits for some recipients and their informal caregivers. Paid assistance might substitute for informal care and cost government more than alternative arrangements; however, the relative total costs to recipients and society are unknown.
We, a team of Cochrane researchers, searched widely through the medical literature and identified 42 relevant studies involving 1453 participants. The evidence is current to January 2015. The participants in these studies had some control of their affected arm and were generally able to open their affected hand by extending the wrist and fingers. CIMT treatments varied between studies in terms of the time for which the participants' unaffected arm was constrained each day, and the amount of active exercise that the affected arm was required to do. CIMT was compared mainly to active physiotherapy treatments, and sometimes to no treatment. The 42 studies assessed different aspects of recovery from stroke, and not all measured the same things. Eleven studies (with 344 participants) assessed the effect of CIMT on disability (the effective use of the arm in daily living) and found that the use of CIMT did not lead to improvement in ability to manage everyday activities such as bathing, dressing, eating, and toileting. Twenty-eight trials (with 858 participants) tested whether CIMT improved the ability to use the affected arm. CIMT appeared to be more effective at improving arm movement than active physiotherapy treatments or no treatment. The quality of the evidence for each outcome is limited due to small numbers of study participants and poor reporting of study details. We considered the quality of the evidence to be low for disability and very low for the ability to use the affected arm.
This review included 15 trials with a total of 718 participants. The findings suggested that cognitive stimulation has a beneficial effect on the memory and thinking test scores of people with dementia. Although based on a smaller number of studies, there was evidence that the people with dementia who took part reported improved quality of life. They were reported to communicate and interact better than previously. No evidence was found of improvements in the mood of participants or their ability to care for themselves or function independently, and there was no reduction in behaviour found difficult by staff or caregivers. Family caregivers, including those who were trained to deliver the intervention, did not report increased levels of strain or burden. The trials included people in the mild to moderate stages of dementia and the intervention does not appear to be appropriate for people with severe dementia. More research is needed to find out how long the effects of cognitive stimulation last and for how long it is beneficial to continue the stimulation. Involving family caregivers in the delivery of cognitive stimulation is an interesting development and merits further evaluation.
We included six randomised controlled trials (reported in nine publications), reporting data on a total of 576 adult participants, who underwent pancreaticoduodenectomy for any pancreatic disease. The evidence is current to September 2015. We did not identify significant differences in delayed gastric emptying; postoperative mortality; postoperative pancreatic fistula, or other complications; reoperations; or length of hospital stay. Quality of life, only reported for a subset of participants in one trial, did not differ between the two groups. Our results do not suggest any relevant differences between antecolic and retrocolic reconstruction of the gastro- or duodenojejunostomy after partial pancreaticoduodenectomy. The quality of the evidence was only low to moderate, due to clinical and statistical differences between individual trials, and risk of bias, due to shortcomings in the way the trials were conducted. Therefore, the results should be viewed with caution.
The review authors found 31 trials (involving 17,771 women) that looked at the impact of providing folic acid supplementation during pregnancy. The data showed that taking folate during pregnancy was not associated with reducing the chance of preterm births, stillbirths, neonatal deaths, low birthweight babies, pre-delivery anaemia in the mother or low pre-delivery red cell folate, although pre-delivery serum levels were improved. The review also did not show any impact of folate supplementation on improving mean birthweight and the mother’s mean haemoglobin levels during pregnancy compared with taking a placebo. However, the review showed some benefit in indicators of folate status in the mother. The evidence provided so far from these trials did not find conclusive results for any overall benefit of folic acid supplementation during pregnancy. Most of the studies were conducted over 30 to 45 years ago.
The studies in this review took place in 12 different countries. They evaluated either the effects of introducing user fees; removing fees; or increasing or decreasing fees. The studies varied according to the type of health services and the level and nature of payment. While some of the studies looked at the impact of large-scale national reforms, other studies looked at small-scale pilot projects. All of the evidence was of very low quality and the studies showed mixed results: When user fees were introduced or increased: - People’s use of preventive healthcare services decreased. - People’s use of curative services generally decreased. However, when quality improvements were made to the health services at the same time as fees were introduced, people’s use of curative services increased. In addition, poor parts of the population began to use health care services more. When user fees were removed: - There was usually no immediate impact on people’s use of preventive healthcare services. But in several cases, people’s use of these services did increase after some time. - There was some increase in the number of outpatient visits, but no increase in the number of inpatient visits. When user fees were decreased: - There was an increase in the use of preventive and curative healthcare services, ranging from a very small to a large increase. To summarise, results were mixed and the quality of the evidence was very low. We are therefore uncertain about the effects of user fees on health service use.
This systematic review was aimed at determining whether any medical treatment decreased blood loss and decreased allogeneic blood transfusion requirements in patients undergoing liver resections. This systematic review included six trials with 849 patients. All trials had high risk of bias ('systematic error') as well of play of chance ('random error'). The trials included comparison of medicines (such as aprotinin, desmopressin, recombinant factor VIIa, antithrombin III, and tranexamic acid) with controls (no medicines). There was no difference in the death or complications due to surgery or long-term survival in any of the comparisons. Fewer patients required transfusion of blood donated by others when aprotinin or tranexamic acid were compared to controls not receiving the interventions. The other comparisons did not decrease the transfusion requirements. However, there is a high risk of type I errors (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included and the small sample size in each trial as well as the inherent risk of bias (systematic errors). Aprotinin and tranexamic acid show promise in the reduction of blood transfusion requirements in liver resections. Further randomised clinical trials with low risk of bias (systematic errors) and low risk of play of chance (random errors) which assess clinically important outcomes (such as death and complications due to operation) are necessary to assess any pharmacological interventions aimed at decreasing blood transfusion and blood transfusion requirements in liver resections. Trials need to be designed to assess the effect of a combination of different interventions in liver resections.
We included seven trials involving 521 patients for this review. The number of patients included in the trials varied from 12 to 180. The comparisons performed included whether antibiotics are necessary routinely during the peri-operative period of liver resection, the duration of antibiotics, and the use of other agents to improve the general body resistance to infection. There was no difference in the risk of death or in the major complication rates between the compared groups in any of the comparisons. Quality of life was not reported in any of the trials. All the trials were of high risk of systematic errors (ie, there was a potential to arrive at wrong conclusions because of the way the trial was conducted) and random errors (there was a potential to arrive at wrong conclusions because of play of chance). We are unable to advocate or refute any method of decreasing infectious complications after liver resection. Further well designed trials with low risk of systematic error and low risk of random errors are necessary.
We identified five trials involving 836 participants who had open abdominal operations. Peritoneal closure was done in 410 participants and not done in 426. All trials had a high risk of bias. Only one trial reported the proportion of participants who died up to one year after the operation, and there was no significant difference between the closure and non-closure groups. Three trials reported major wound breakdown (burst abdomen), which requires emergency surgery. Overall, 10/663 participants (1.5%) developed burst abdomen, with no significant difference in proportions between the two groups. Three trials reported minor wound breakdown (incisional hernia), that may require surgery. Overall, 17/663 participants (2.5%) developed incisional hernia; again there was no significant difference between the two groups. None of the trials reported on important outcomes, such as quality of life; the occurrence of intestinal obstruction (caused by intestines sticking to themselves and the abdominal wall (adhesions)); or the proportion of participants who had surgery to fix incisional hernia or adhesions. Only one trial reported length of hospital stay, and showed no significant difference between the groups, but did not include readmissions in its calculations. There does not appear to be any evidence for a short-term or long-term advantage in peritoneal closure in operations not related to childbirth. However, the trials were at high risk of bias, which can lead to false conclusions. Interestingly, our findings are similar to those of another research group who performed a similar review for operations related to childbirth.
The review shows that treatment with artemisinin drugs may be better than quinine at preventing death in adults and children with severe and complicated malaria. There is no evidence so far against early treatment with suppositories in rural areas whilst patients are transferred to hospital. Few side effects have been reported with these drugs.
This review found five randomised controlled trials that involved a total of 960 women. They looked at a variety of preventive interventions including breastfeeding education, taking antibiotic medication, topical ointments and anti-secretory factor cereal. None of the therapies made any difference in reducing breast infections or the length of breastfeeding exclusivity and duration with this limited evidence. Generally studies were of low quality, with limited findings highlighting the need for better quality research in this area.
This methodology review identified five studies which investigated the effect of including trials found in the grey literature in systematic reviews of health care interventions. They showed that trials found in the published literature tend to be larger and show larger effects of a health care intervention than those trials found in the grey literature. There was limited evidence to show whether grey trials are of poorer methodological quality than published trials. This means that those carrying out systematic reviews need to search for trials in both the published and grey literature in order to help minimise the effects of publication bias in their review.
This review found 13 studies including 254 patients with type 1 and type 2 diabetes. Reducing salt intake by 8.5 g/day lowered BP by 7/3 mm Hg. Public health guidelines recommend reducing dietary salt intake to less than 5-6 g/day and people with diabetes would benefit from reducing salt in their diet to at least this level.
This evidence is current to May 2014. We identified five randomised controlled trials (1296 participants under two years of age) comparing montelukast (a leukotriene inhibitor) with placebo in infants and young children hospitalised with bronchiolitis. Our primary outcomes were length of hospital stay and all-cause mortality. Secondary outcomes included clinical severity score, percentage of symptom-free days, percentage of children requiring ventilation, recurrent wheezing, oxygen saturation, respiratory rate and clinical adverse effects. The effects of montelukast on length of hospital stay and clinical severity score were uncertain due to considerable heterogeneity (differences) between the study results and wide confidence intervals around the estimated effects. Data on symptom-free days and incidence of recurrent wheezing were from single studies only and individual analyses of these studies did not show significant differences between the intervention group and the control group. One study of 952 children reported two deaths in the leukotriene inhibitors group: neither was determined to be drug-related. No data were available on the percentage of children requiring ventilation, oxygen saturation and respiratory rate. Finally, three studies reported adverse events including diarrhoea, wheezing shortly after administration and rash. No differences were reported between the study groups. We assessed the quality of the evidence for length of hospital stay and clinical severity score as low due to inconsistency and imprecision arising from small sample sizes and wide confidence intervals, which did not rule out no effect or harm. Overall, the current evidence does not allow definitive conclusions to be made about the effect and safety of leukotriene inhibitors in infants and young children with bronchiolitis.
We searched the databases to September 2012, to find controlled trials that had randomly assigned obese participants (with body mass index (BMI) greater than 30 kg/m2) undergoing general anaesthesia to TT or SAD for airway management. We wanted to investigate the effect of airway type on risk of failed placement; serious complications and death; oxygenation of the blood during and after surgery; coughing, sore throat or hoarseness during or after placement; and time taken and number of attempts needed to fit the airway. We found two randomized studies with a total of 232 obese participants, both of which studied one model of SAD－the ProSeal laryngeal mask airway (PLMA). No relevant outcomes for death or other serious complications occurred in these studies.We found that in 3% to 5% of obese participants, it was not possible to fit a PLMA, and a change of device to a TT was required. The proportion of successful first attempts at airway placement did not differ between PLMA and TT, although it took approximately six seconds longer to place an SAD than a TT. We found significant postoperative reduction of almost 75% in episodes of low oxygen saturation and an improvement in mean oxygen saturation of 2.5% during recovery in the PLMA group. Postoperative cough was less common among participants in the PLMA group. Our findings are consistent with both increased and decreased risks of both sore throat and hoarseness in the PLMA group. Identifying optimal anaesthetic techniques for obese patients is a priority for research. We could not establish the safety of SAD use in obese patients. Large databases created from medical records may be needed to clarify this issue.
Surgery to bypass the blockage uses either a piece of vein from another part of the person’s body or a synthetic graft. The bypass may help improve blood supply to the leg but the graft can also become blocked, even in the first year. To help prevent this, people are given aspirin (an antiplatelet drug) or a vitamin K antagonist (anti-blood clotting or antithrombotic drug), or both, to try to stop loss of blood flow through the graft (patency). The review of trials found that patients undergoing venous grafts were more likely to benefit from treatment with vitamin K antagonists than platelet inhibitors. Patients receiving an artificial graft may benefit from platelet inhibitors (aspirin). However, the evidence is not conclusive. Although a total of 14 randomised, controlled trials involving 4970 patients were included in the review, trials with larger patient numbers are needed. This is because there was considerable variation between the included trials in whether patients received both types of drugs, anticoagulation levels and how they were measured, and the indications for surgery, intermittent claudication or critical limb ischaemia.
No studies reported the effect of meglitinides on mortality or diabetes related complications. In the eleven studies comparing meglitinides to placebo, both repaglinide and nateglinide resulted in an improved blood sugar control. Weight gain was generally greater in those treated with meglitinides compared with metformin (up to three kg in three months), another oral antidiabetic drug. Here, diarrhoea occurred less frequently and hypoglycaemia occurred more frequently but rarely severely enough as to require assistance.  Meglitinides may offer an alternative oral hypoglycaemic agent of similar potency to metformin, and may be indicated where side effects of metformin are intolerable (in particular persistent diarrhoea) or where metformin is contraindicated. However, there is no evidence available yet to indicate what effect meglitinides will have on important long-term outcomes, in particular, on mortality. As yet, the experience with meglitinides in terms of side effects is limited. Results from other Cochrane review groups may provide additional information about the potential role of meglitinides in the management of type 2 diabetes mellitus.
We included in our analysis six studies (1412 people overall), four of which (437 people) examined effects of cooling the body by conventional methods after successful resuscitation for cardiac arrest. One study that used haemofiltration (cooling the blood externally - similar to dialysis) as the cooling method and one study in which cooling to 33°C was compared with temperature management at 36°C were treated separately in the review. The study that used external cooling was supported by a dialysis-related company. Of the five studies included in the main analysis, two received funding from government or non-profit organizations; three studies did not provide information on funding. When we compared people whose bodies were cooled to 32°C to 34°C after resuscitation versus those whose bodies were not cooled at all, we found that 63% of those receiving cooling would suffer no, or only minor, brain damage, while only 33% of those not cooled would suffer no, or only minor, brain damage. Cooling had an important effect on simple survival, with or without brain damage: 57% would survive if their bodies were cooled compared with 42% if their bodies were not cooled at all. No serious side effects occurred, but cooling the body was associated with increased risk of pneumonia (49% vs 42% of those studied) and increased risk of low concentrations of potassium in the blood (18% vs 13%). Some studies had quality shortcomings including small numbers of participants and use of inadequate methods to balance participants between intervention and control groups. However, when differences between studies are acknowledged (heterogeneity), it is clear that these shortcomings had no major impact on the main results.
We found eight randomised controlled trials comparing long-term GnRH agonist therapy with no pretreatment including a total of 640 women with endometriosis prior to IVF/ICSI. The evidence is current to January 2019. Compared to no pretreatment, we are uncertain whether long-term GnRH agonist therapy prior to IVF/ICSI in women with endometriosis affects the live birth rate. The evidence suggests that if the chance of live birth rate is assumed to be 36% with no pretreatment, the chance following long-term GnRH agonist therapy would be between 9% and 31%. We are also uncertain whether this intervention affects complication rate, clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, mean number of oocytes and mean number of embryos. No studies compared long-term GnRH agonist therapy to long-term continuous COC therapy or surgery to remove endometriomas. The evidence was of very low quality. The main limitations in the evidence were lack of blinding (the process where the women participating in the trial, as well as the research staff, are not aware of the intervention used), inconsistency (differences between different studies) and imprecision (random error and small size of each study).
Fifteen studies which lasted between 4 to 24 weeks including a total of 1219 participants were analysed. Trials of chitosan to date have varied considerably in terms of quality. The review suggests that chitosan may have a small effect on body weight but results from high quality trials indicate that this effect is likely to be minimal.
The objective of this review was to assess whether any form of psychotherapy is effective in the management of people suffering from hypochondriasis. Six studies were included in the review. Analysis of data suggested that, compared to being on a waiting list, forms of cognitive and behaviour therapy, or a non-specific therapy called behavioural stress management all improve the symptoms of hypochondriasis. However, the numbers of people in the studies were small and it was not possible to tell how much of an improvement each therapy made. It is possible that the improvements seen were due to non-specific factors involved in regular contact with a therapist rather than specific properties of these forms of psychotherapy. It was also not possible to make comparisons between the different types of psychotherapy. A study of psychoeducation was not considered to be sufficient evidence that this form of psychotherapy is effective.
The evidence is current to April 2014. We found three studies (from four reports) involving a total of 22 children aged three to nine years who received a combination of NSOMTs and articulation or phonological therapy (intervention group), or articulation or phonological therapy alone (control group). One study was a randomised controlled trial in which four boys with speech sound disorders were randomly assigned to one of the two groups. In this study, each participant received 16 × 30-minute individual therapy sessions, twice per week over eight weeks, to treat the speech sound 's'. For the intervention group, NSOMT (oral placement therapy) was conducted in the first 10 minutes of each session, followed by 20-minute articulation therapy. The other two studies used randomisation, but the method used to generate the random sequence was not reported. In one of these studies, six boys and four girls, all with speech sound disorders due to tongue thrust, were randomly assigned to one of the two groups. Each participant received 22 × 30-minute individual sessions conducted weekly in the first six weeks, and twice a week in the following eight weeks, to treat 's' and 'z' sounds. The intervention group received NSOMT (Hanson's 1977 approach) in the first six weeks and alternating sessions of NSOMT and articulation therapy in the following eight weeks. The final study randomly assigned four boys and four girls with moderate to severe articulation disorder alone to either intervention group or control group. Each participant received 9 × 20-minute group therapy sessions (two participants in each group), conducted twice a week over five weeks. For the intervention group, NSOMT (oral motor exercises for speech clarity) was conducted during the first 10 minutes of each session. Speech errors associated with the 's' sound were treated for the intervention group; however, the speech sound(s) treated for the control group were not detailed. None of the studies reported funding support. Two studies (one that used oral placement therapy and one that used Hanson's 1977 approach) did not find NSOMT as an adjunctive treatment to be more effective than conventional speech intervention only, as both intervention and control groups had made similar improvements in articulation after treatment (i.e. fewer speech errors or increased percentage of correct articulation). The study that used oral motor exercises for speech clarity as the NSOMT reported a change in articulation test results after treatment, but used an inappropriate statistical test and did not report the results clearly. The three included studies were small in scale and had a number of serious methodological limitations. Moreover, these studies covered limited types of NSOMTs for treating just one class of speech sounds - 's' with or without 'z' - in children with speech sound disorders. Hence, the overall applicability of the evidence is limited, and the evidence is believed to be incomplete and of low quality. To conclude, currently no strong evidence indicates whether NSOMTs are effective as treatment or adjunctive treatment for children with developmental speech sound disorders.
This Cochrane review assessed the effects of six-month regimens for treating people with TBM compared with longer regimens. Cochrane researchers examined the available evidence up to 31 March 2016 and they included 18 studies. None of the included studies directly compared people with TBM treated for six months with people with TBM treated for longer. Two of the included studies analysed two groups of participants treated for six months and longer than six months. Therefore, the review authors included information from seven groups of people treated for six months (458 people), 12 groups of people treated for longer than 6 months (1423 people), and one ongoing study of 217 people which was analysed separately due to methodological concerns. Although the treatment regimens in the included studies varied, most participants received standard first-line antituberculous drugs, and were followed up for more than a year after the end of treatment. The studies included adults and children with TBM, but few participants were HIV-positive. Relapse was an uncommon event across both groups of studies, with only one death attributed to relapse in each group. Most deaths occurred during the first six months of treatment in both groups of studies, which showed that treatment duration did not have a direct impact on the risk of death in these studies. There was a higher death rate in participants treated for longer than six months, and this probably reflects the differences between the participants in the two groups of studies. Few participants defaulted from treatment, and adherence was not clearly documented. They found no evidence of high relapse rates in people treated for six months, and relapse was uncommon in all patients irrespective of regimen. There may be differences between the participants treated for six months and longer than six months that could have led to bias (confounding factors), so further research would help determine if shorter regimens are safe. Most of the data were in patients without HIV, and so these inferences do not apply to patients who are HIV-positive.
Fifteen trials met the inclusion criteria and are included in the review. Interpretation of the results was hindered by the small total sample size and by the low quality of reporting of the included trials. There was some evidence that haloperidol was more efficacious than placebo in terms of reduction of manic and psychotic symptom scores, when used both as monotherapy and as add-on treatment to lithium or valproate. There is no evidence of difference in efficacy between haloperidol and risperidone, olanzapine, valproate, carbamazepine, sultopride and zuclopentixol. There was a statistically significant difference with haloperidol being probably less effective than aripiprazole. No comparative efficacy data with quetiapine, lithium or chlorpromazine were reported. Haloperidol caused more extrapyramidal symptoms (EPS) than placebo and more movement disorders and EPS but less weight gain than olanzapine. Haloperidol caused more EPS than valproate but no difference was found between haloperidol and lithium, carbamazepine, sultopride and risperidone in terms of side effects profile.
In the present study haloperidol treatment was associated with a lower degree of aggression than was placebo. Adverse effects occurred more frequently in haloperidol treated patients than controls, but similar drop-out rates among treated and control patients suggested that for some patients adverse effects may have been tolerated because of better control of behaviour. Our findings indicated that there is little evidence to support a benefit of haloperidol on manifestations of agitation other than aggression, and that haloperidol should not be used routinely to treat patients with agitated dementia. Treatment of agitated dementia should be individualized, with careful monitoring of benefits and adverse effects.
This updated review included nine studies that evaluated integrated care or linkages in care. The studies made two types of comparison. 1) Integration of care, by adding a service to an existing service (tuberculosis (TB) or sexually transmitted infection (STI) patients were offered HIV testing and counselling; mothers attending an immunisation clinic were encouraged to have family planning services). 2) Integrated services versus single, special services (family planning, maternal and child health delivered as a special vertical programme or integrated into routine healthcare delivery). There was some evidence from the included studies that adding on services or creating linkages to an existing service improved its use and delivery of health care but little or no evidence that fuller integration of primary healthcare services improved people's health status in low- or middle-income countries. People should be aware that integration may not improve service delivery or health status.If policy makers and planners consider integrating healthcare services they should monitor and evaluate them using good study designs. A summary of this review for policy-makers is availablehere
We identified 16 randomised clinical trials (trials where participants are randomly allocated to treatment groups) including 827 participants. The included people had cirrhosis often due to alcoholic liver disease or viral hepatitis (liver infection due to a virus). The trials compared BCAA with placebo (a pretend treatment), no intervention, diets, lactulose (a liquid sugar often used to treat constipation), or neomycin (an antibiotic). The evidence is current to October 2014. The analyses found no effect on mortality, but that BCAA had a beneficial effect on symptoms and signs of hepatic encephalopathy. BCAA did not increase the risk of serious adverse events, but was associated with nausea and diarrhoea. When excluding trials on lactulose or neomycin, BCAA had a beneficial effect on hepatic encephalopathy. When analysing trials with a lactulose or neomycin control, we found no beneficial or detrimental effect of BCAA. We assessed the quality of the evidence to evaluate aspects that can lead to errors in the judgment of intervention effects. We concluded that we had high quality evidence in our analyses about the effect of BCAA on hepatic encephalopathy. We concluded that we had moderate or low quality evidence in the remaining analyses because the number of participants in the trials was too small and the risk of bias (systematic errors) was unclear or high.
We searched the literature until April 2015 and found no new trials for this update. We found four trials for the previous updates. We included four trials in our review and report that people receiving end-of-life care at home are more likely to die at home. It is unclear whether home-based end-of-life care increases or decreases the probability of being admitted to hospital. Admission to hospital while receiving home-based end-of-life care varied between trials. People who receive end-of-life care at home may be slightly more satisfied after one month and less satisfied after six months. It is unclear whether home-based end-of-life care reduces or increases caregiver burden. Healthcare costs are uncertain, and no data on costs to participants and their families were reported. People who receive end-of-life care at home are more likely to die at home. There were few data on the impact of home-based end-of-life services on family members and lay caregivers.
The available evidence from randomized controlled trials supports the use of subacromial corticosteroid injection for rotator cuff disease, although its effect may be small and short-lived, and it may be no better than non-steroidal anti-inflammatory drugs. Similarly, intra-articular steroid injection may be of limited, short-term benefit for adhesive capsulitis. Further trials investigating the efficacy of corticosteroid injections for shoulder pain are needed. Important issues that need clarification include whether the accuracy of needle placement, anatomical site, frequency, dose and type of corticosteroid influences efficacy.
This is an update of previous reviews. We searched for studies published up to April 2018, and found three new studies that we could include, giving a total of 14 studies with 3370 participants. Studies had to be randomised controlled trials that recruited smokers trying to quit, and measured whether participants had quit smoking at least six months after the beginning of the study. The study had to include at least one group who were part of a stop-smoking programme to increase partner support, and at least one group who received a comparable stop-smoking programme without partner support. Most of the studies were conducted in the USA. At recruitment the average amount participants smoked was between 13 to 29 cigarettes a day across studies. The smoking status of partners providing support varied, but most were non-smokers. Intervention techniques ranged from low to high intensity; in some cases help was by a self-help booklet and in other cases by face-to-face counselling. In some studies researchers did not make direct contact with 'partners' and the smokers themselves were encouraged to find a 'buddy', but in other studies both the smoker and their 'buddy' received face-to-face support. We combined 12 studies (2818 participants) to measure successful quitting at six to nine months follow-up, and seven studies (2573 participants) to measure quitting at 12-month follow-up. Partner support did not increase the chances of stopping smoking at either time point. We also split the studies in each analysis based on the type of partner giving support (relatives/friends/co-workers versus spouses/cohabiting partners versus fellow cessation-programme participants). There was no difference in quit rates between study groups, regardless of the type of partner providing the support. Only one study reported that partner support improved more in the group given the partner-support intervention than in the group where no partner-support intervention was provided. Another study reported that partner support improved more in a more intensive partner-support intervention than a less intensive partner-support intervention. We rated the overall quality of the evidence as low. This is because there were problems with the design of some of the studies. A number of important studies only used participant self-report to measure if people had quit smoking, and there is a chance that these reports may have been inaccurate. Also, very few studies found that the intervention actually increased the level of partner support that participants received. This review therefore cannot tell us whether receiving more support from a partner can help a person to give up smoking.
The review looked for studies that examined the effectiveness of this treatment in improving movement and reducing the death rate. Nearly all the research, seven trials, has involved just one steroid, methylprednisolone. The results show that treatment with this steroid does improve movement but it must start soon after the injury has happened, within no more than eight hours. It should be continued for 24 to 48 hours. Different dose rates of the drug have been given and the so-called high-dose rate is the most effective. The treatment does not, however, give back the patient a normal amount of movement and more research is necessary with steroids, possibly combining them with other drugs.
Maternal advice and support on feeding techniques and breastfeeding positions are often provided, but no studies evaluated the effectiveness of this intervention. Squeezable rather than rigid bottles may be easier to use for feeding babies with cleft lip and/or palate, and breastfeeding may have growth advantages over spoon-feeding following cleft lip surgery. Only five studies (including 292 babies) compared the effects of feeding interventions in babies with cleft lip and/or palate on growth, development or parental satisfaction. Evidence for breastfeeding rather than spoon-feeding following surgery was weak and there was a suggestion that squeezable bottles may be more manageable than rigid ones. No evidence was found to support the use of maxillary plates in babies with unilateral clefts and no studies assessed the effects of maternal advice or support. Further research is required to assess the most effective feeding interventions to prevent developmental delays in infants with cleft lip and/or palate.
We identified eight studies that were eligible for this Cochrane Review. All studies had both primary and secondary prevention components. That is, they targeted students known to be suicidal as well as those not known to be suicidal. We separately analysed the effects of classroom instruction, institutional policies, and gatekeeper training programs. Gatekeeper training programs train people to recognize and respond to warning signs of emotional crises or suicide risk in students they encounter. The evidence is current to June 2011. Three studies, including 312 students, evaluated classroom instruction. Classroom instruction increases short-term knowledge of suicide and suicide prevention. It may slightly enhance short-term confidence in ability to prevent suicide. However, long-term effects have not been studied. Effects of classroom instruction on suicidal behavior have also not been studied. One study evaluated an institutional policy. The policy restricted access to laboratory cyanide and required professional assessment for students who threatened or attempted suicide. The policy significantly reduced student suicides. These findings have not been tested in other post-secondary institutions. Four studies, ranging from 53 to 146 participants, evaluated the effect of gatekeeper training programs. Gatekeeper training may lead to small-to-medium improvements in short-term suicide-related knowledge and confidence about being able to prevent suicide. We found no evidence that gatekeeper training improved short-term attitudes toward suicide or long-term knowledge or behaviors about suicide. The effect of gatekeeper training on suicide or suicidal behavior has not been evaluated. The quality of evidence for short-term knowledge of suicide and suicide prevention was moderate. For suicide prevention self-efficacy, the quality of evidence was low. The quality of evidence was reduced because results were not similar across studies and there were not enough data.
Oral anticoagulants prevent stroke and death in people with atrial fibrillation. Atrial fibrillation is an irregularity of the heartbeat that leads to blood clots forming in the upper chambers of the heart (the atria). These clots can break free and travel through the blood stream to the brain and cause a stroke. Anticoagulant drugs, such as warfarin, slow blood clotting. The degree of inhibition of blood clotting during warfarin treatment is measured by a blood test called the international normalized ratio (INR). Dosages of warfarin that lead to INRs of 2.0 to 2.6 reduce death and stroke when given to patients with atrial fibrillation. Oral anticoagulants can cause bleeding into the brain and elsewhere. However, provided that there is careful control of dosage (requiring INR measurements at least monthly with warfarin), the risk of serious bleeding is low. The decision about whether or not to use oral anticoagulants in patients with atrial fibrillation is guided by a number of factors, including the individual's risk of stroke, which varies widely among patients with atrial fibrillation. Most people with atrial fibrillation should be considered for treatment with oral anticoagulants based on their risk of stroke, ability to tolerate anticoagulation without bleeding, and access to adequate anticoagulation monitoring.
For this update of a previous Cochrane review, we reviewed the available evidence up to January 2015 for or against feverfew in the prevention of migraine and found six studies including 561 participants. Generally the studies were heterogeneous and their results were mixed. The previous version of this review showed no clear benefit of feverfew compared with placebo. We added a new study, which is larger and was carried out to high standards, to this review. It showed that feverfew reduced migraine frequency by a little more than half a migraine (0.6) per month compared to placebo. There was no difference in how severe the pain was, or how long it lasted. These results come from a single study of moderate size, therefore they must be viewed with caution until they are confirmed in other rigorous studies. No major adverse effects were associated with feverfew in the included studies.
In this review we found two randomised controlled trials which studied PCV in recurrent HGG patients. The comparator was Temozolomide (TMZ) in one and 'eight drugs in one day' multidrug chemotherapy in another. Results of the two trials were not combined because they compared PCV with different treatments. Conclusions should be drawn with caution as they are based on a single trial analysis as the other trial was too small and underpowered to detect significant difference. Adverse effects and QoL results are based on a single trial analysis. The proportion of participants experiencing severe adverse events with PCV was similar to TMZ. QoL scores were higher with TMZ but not clinically significant. We attributed moderate-grade quality of evidence for overall survival, progression-free survival, chemotherapy toxicity and low-grade evidence for QoL. Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes. Adverse events are similar and QoL scores are statistically but not clinically important between TMZ and PCV. The results do not apply to our contemporary patients with recurrent HGG as most of them would receive chemotherapy after original diagnosis as standard care. Participants in this trial received only radiotherapy prior to recurrence. Molecular markers were not used in decision making, which is the standard of care now.
We found 28 relevant randomized controlled studies, conducted between 1994 and 2015. Most of the 4438 adults who participated in these studies were undergoing first-time elective coronary artery graft bypass or valve replacement surgery, or both. They were at low to moderate risk of death after surgery. Eighteen studies examined the use of low-dose opioid-based general anaesthesia. Sixteen studies assessed how effective the protocols were in guiding staff to remove the tube that provided breathing support within eight hours after surgery. We found no differences in risk of death in the first year after surgery (18 trials, 3796 participants) nor in complications after surgery such as the need to replace the tracheal tube after surgery (17 trials, 1855 participants) and occurrence of myocardial infarction (16 trials, 3061 participants) or stroke (16 trials, 2208 participants), when we examined both types of interventions. Occurrences of acute renal failure, major bleeding, sepsis and wound infection also were not different. We rated the quality of evidence as low for both mortality and postoperative complications. Tracheal tubes were removed from adults in the fast-track care group up to a half day earlier than for those in the conventional care group. The fast-track group spent less time in the intensive care unit, but length of time spent in the hospital was similar between groups. The quality of evidence was low because of study limitations and unexplained variation in study findings. Large trials were few, and only one trial was designed to study postoperative effects of myocardial infarction, stroke or death. Our results did not apply to ‘high-risk' patients who had multiple concurrent health problems or to settings in which a short-acting opioid (remifentanil) was used for general anaesthesia. Fast-track cardiac care is safe in patients considered to be at low to moderate risk of death after surgery.
We analysed six studies that investigated the use of several different types of antibody therapies in 278 adult patients following lung transplantation. Flaws in study designs were found that indicated the studies were at risk of overestimating benefits and underestimating harms. Our analysis compared several types of antibodies, but with one exception - that antithymocyte globulin seemed to increase some adverse events - we found no significant differences in lung survival or rejection for any of the treatments. There was some uncertainty about this effect because the study was too small to be sure that observed benefits would apply to a larger population. We found no significant differences among therapies in terms of infection, bronchiolitis obliterans syndrome, post-transplantation lymphoproliferative disease, or cancer. Few investigated the use of T-cell antibodies after lung transplantation, and these included small numbers of participants. These limitations meant that our findings did not necessarily indicate no differences existed among comparisons in our analysis. To overcome this problem, larger and more robust randomised studies that assess the benefits and harms of antibodies against T-cells for people following lung transplantation are needed.
In December 2016 and January 2017, we searched for clinical trials on the addition of ketamine to morphine-like drugs for cancer pain. We found one new study, together with the two studies included in the original review. The three studies were very different, using different doses of ketamine, different routes of administration and different durations of treatment and it was not possible to combine the results of these studies. The two smallest studies reported that the addition of ketamine to morphine reduced pain intensity and morphine requirements. The third study which used high doses of ketamine reported no clinical benefit of adding ketamine to different opioids. Increased doses of ketamine in some participants caused side effects such as hallucinations. The study which examined high doses of ketamine reported two serious adverse events, which may have been related to ketamine. Although two out of three studies reported reduction in pain, this could be due to chance in such small studies. We rated the quality of the evidence using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The evidence from the studies was of very low quality. There were problems with the design of some studies and there were not enough data to answer some parts of our review question.
This review of studies has established that there is evidence for useful effects of these drugs in terms of symptom relief and lung function, but also some evidence of side-effects. As a primary preventative therapy, whilst there is evidence that xanthines are effective, this review suggests that more effective alternative treatment options (inhaled steroids) are available. In children with more severe asthma, the role of xanthines as an add-on therapy has only been assessed in a small number of trials, which report mixed effects. More studies in this area would help to generate a more reliable overview of the effects of treatment in these children. Xanthines are an effective preventative treatment in childhood asthma, but less effective than inhaled steroids, and with a less favourable side-effect profile. There is insufficient evidence at present to assess their role as "add-on" preventer treatment versus newer alternatives. Some of the trials exposed the children they recruited to a pre-trial phase of xanthine in order to maintain effective dosing during the trial. This could have made the trial participants less representative of the general population by making them more inclined to tolerate the study drug. This exposure also may have meant that they could recognise what drug they were taking during the blinded phase of the study.
We included 10 studies with a total number of 165 participants. The studies examined the short- and medium-term effect of music therapy interventions (one week to seven months) for children with ASD. Music therapy was superior to 'placebo' therapy or standard care with respect to social interaction, non-verbal and verbal communicative skills, initiating behaviour, and social-emotional reciprocity. Music therapy was also superior to 'placebo' therapy or standard care in the areas of social adaptation, joy, and the quality of parent-child relationships. None of the included studies reported any side effects caused by music therapy. The quality of the evidence was moderate for social interaction outside of the therapy context, initiating behaviour, social adaptation, and the quality of the parent-child relationship, and low for the other three main outcomes (nonverbal communicative skills outside of the therapy context, verbal communicative skills outside of the therapy context, and social-emotional reciprocity). Reasons for limited quality of the evidence were issues with study design and small number of patients who participated in the studies. Music therapy may help children with ASD to improve their skills in important areas such as social interaction and communication. Music therapy may also contribute to increasing social adaptation skills in children with ASD and to promoting the quality of parent-child relationships. Some of the included studies featured interventions that correspond well with treatment in clinical practice. More research with adequate design and using larger numbers of patients is needed. It is important to specifically examine how long the effects of music therapy last. The application of music therapy requires specialised academic and clinical training. This is important when applying the results of this review to practice.
We found one study from the United Kingdom involving 80 people with bronchiectasis. The study was completed in 2002, when management of bronchiectasis was different from today. Participants were divided into two groups: One group of outpatients was observed for a 12-month period under the care of the specialist nurse, and the other under care of the doctor. After 12 months, these participants swapped groups. We found no significant differences between nurse-led and doctor-led care in terms of lung function, infective flareups (exacerbations), or quality of life. In the first year of the study we noted increased costs for nurse-led care with more hospital admissions and greater use of antibiotic injections. The certainty of evidence in the one included study was satisfactory, given that the study design meant participants knew which group they belonged to. More research is required to determine how nurse specialists compare with doctors in providing safe and effective treatment for patients with stable bronchiectasis. This Cochrane plain language summary was up-to-date as of March 2018.
The review of trials examined the effects of giving people with cancer audio recordings or written summaries of consultations. Most people found them useful as a personal reminder, to inform their families or friends, or to play to their general practitioners. People tended to remember more of the information they were given, and some were more satisfied with the information they received. Recordings or summaries did not make people more anxious or depressed. The recordings had no effects on quality of life, and no studies measured survival.
We examined the research published up to November 2014. We included 10 randomised trials (836 participants). Two studies included subjects with subacute NP (337 participants), while the other eight studies included participants with chronic NP (499 participants). CBTwas compared to no treatment (225 participants) or to other types of treatments (506 participants), or combined with another intervention (e.g. physiotherapy) and compared to the other intervention alone (200 participants). The interventions were carried out at primary and secondary health care centres. With regard to chronic NP, CBT was statistically significantly better than no treatment at improving pain, disability, and quality of life, but these effects could not be considered clinically meaningful. No differences between CBT and other types of interventions (e.g. medication, education, physiotherapy, manual therapy, and exercises) were found in terms of pain and disability; there was moderate quality evidence that CBT was better than other interventions in improving fear of movement. Also, there was very low quality evidence that CBT added to another intervention was no better at improving pain and disability than the other intervention alone . For subacute NP, there was low quality evidence that CBT was statistically significantly better than other types of interventions (e.g. manual therapy or education) for improving pain, but this effect was not clinically relevant. No difference was found in terms of disability and fear of movement. None of the included studies reported on whether any adverse effects related to cognitive-behavioural therapy were observed. The quality of evidence in this review ranged between “very low” and “moderate”. Therefore, the review results should be interpreted with caution. More high quality randomised trials are needed to address short and long term benefits of cognitive-behavioural therapy in subacute and chronic neck pain, and its effectiveness compared with other treatments, and to better understand which patients may benefit most from this type of intervention.
Most studies were conducted more than a decade ago, in the USA, in predominantly men. We found that antidepressant therapy may improve depressive symptoms when compared to a placebo tablet. There was no clear evidence of a difference in the number of people who dropped out of care when comparing people who received antidepressants with people who received a placebo. We cannot be certain if one type of antidepressant works better than another. Side effects were very common among all study participants. Although there were no clear conclusions on which side effects were most common or if side effects occurred more frequently in people taking antidepressants compared to a placebo, participants receiving antidepressants called selective serotonin reuptake inhibitors did report sexual problems frequently. People receiving medicines called tricyclic antidepressants reported constipation and dry mouth frequently. No studies reported on how antidepressant therapy affected the effectiveness of antiretroviral therapy. The evidence used to generate several of the results was assessed as low or very low quality. The review authors recommend that new studies on treatment of depression should be conducted in countries and population groups where HIV is most common. These studies should evaluate what causes depression in these populations and how to best to incorporate antidepressant therapy with other strategies for the management of PLWH and depression.
We included 19 clinical trials published up to 3 December 2014, which examined 1346 people. The trials administered TENS to produce a strong non painful 'tingling' sensation at the site of acute pain. The trials assessed TENS for cervical laser treatment, venepuncture, sigmoidoscopy, rib fractures and uterine contractions after childbirth. We did not include trials that assessed TENS for pain associated with childbirth, dental procedures and menstruation because they have been the subject of other Cochrane Reviews. Eleven trials are awaiting classification. TENS was better than placebo TENS (delivering no electrical current) at reducing the intensity of acute pain but the reduction in pain was not consistent across all trials. This finding was based on an analysis of only six of the 19 trials. There was an insufficient number patients to make a firm conclusion. A small number of patients experienced itching and redness beneath the TENS pads or disliked the sensation produced by TENS. Overall we concluded that TENS may reduce the intensity of acute pain in some patients but the quality of evidence was weak. TENS is inexpensive, safe and can be self-administered. We recommended that TENS should be considered as a treatment option given on its own or in combination with other treatments. The quality of the evidence was moderate to low because sample sizes were small and some patients were aware that they were receiving TENS or placebo.
We found 18 studies in 2952 women undergoing IVF or ICSI. Fifteen trials in 2473 women compared rhCG with uhCG, and three trials in 479 women compared rLH with uhCG. Women in the studies were 18 to 45 years old, with regular menstrual cycles and no history of OHSS. Types of subfertility included tubal disease, endometriosis, unexplained infertility and male factor infertility. Pharmaceutical companies funded 9 of the 18 studies; 4 studies were free of commercial funding, and the remaining 5 studies did not clearly report a funding source. The evidence is current to April 2015. There was no evidence of a difference between rhCG and uhCG or between RhLH and uhCG in rates of live birth/ongoing pregnancy or OHSS. Studies did not report much evidence on adverse events other than OHSS, and the evidence they did report was inconclusive. For the comparison 'rhCG versus uhCG', the evidence was of moderate quality for ongoing pregnancy/live birth rate and of low quality for incidence of OHSS. The main limitation of the evidence was lack of precision (i.e. study size was too small to rule out the role of chance). For the comparison 'rLH versus uhCG', the evidence was of very low quality for both ongoing pregnancy/live birth rate and incidence of OHSS. The main limitations of the evidence were lack of precision and poor reporting of study methods.
We found 22 trials to include in the review and we were able to combine results for at least some outcomes from 890 people. All of the people in the trials stayed in nursing homes or hospitals. Some trials compared music-based treatments with usual care, and some compared them with other activities, such as cooking or painting. The quality of the trials and how well they were reported varied, and this affected our confidence in the results. First, we looked at outcomes immediately after a course of therapy ended. From our results, we could be moderately confident that music-based treatments improve symptoms of depression and overall behavioural problems, but not specifically agitated or aggressive behaviour. They may also improve anxiety and emotional well-being including quality of life, although we were less confident about these results. They may have little or no effect on cognition. We had very little confidence in our results on social interaction. Some studies also looked to see whether there were any lasting effects four weeks or more after treatment ended. However, there were few data and we were uncertain or very uncertain about the results. Further trials are likely to have a significant impact on what we know about the effects of music-based treatments for people with dementia, so continuing research is important.
We identified one randomized controlled trial with 262 patients. We excluded other study designs as they give less reliable results. However, randomized studies are difficult to perform in children with neuroblastoma and other evidence might be available. In the identified randomized study, patients with high-risk neuroblastoma were randomized to receive either rapid COJEC or standard OPEC/OJEC induction chemotherapy. Complete response, treatment-related mortality, overall survival, and event-free survival were not different between the two treatment alternatives. Results of both early and late toxicities were not clear cut, for example, some early toxicities were in favor of the standard arm and some late non-hematological toxicities were in favor of the rapid COJEC arm. For other toxicities there was no evidence of a difference between the treatment arms. Data on progression-free survival and health-related quality of life were not reported. Not all biases could be ruled out in this study. Before definitive conclusions can be made more research is needed.
Major depression, also known as major depressive disorder or unipolar depression, is a common mental disorder characterised by a combination of symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy pleasurable activities. An episode of major depression may occur only once in a person's lifetime, but more often, it recurs throughout a person's life. Antidepressant drugs are frequently used as first-line treatment for major depression in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor, is one of the antidepressant drugs that clinicians use for routine depression care in some countries. This systematic review investigated the efficacy, acceptability and tolerability of milnacipran compared to that of other antidepressive agents in the acute phase treatment of major depression. A total of 16 randomised controlled trials (2277 participants) were included in this review. When we brought together the results of approximately 2000 patients, we were unable to say whether milnacipran is better, worse or the same when compared to other antidepressive agents used in practice in terms of efficacy, acceptability and tolerability. However, there is some evidence that fewer people taking milnacipran stop taking the drug ('drop out') due to side effects and fewer people taking milnacipran experience side effects such as sleepiness, dry mouth or constipation than do people who take tricyclic antidepressants.
This review of trials found there were insufficient numbers of participants in the two trials located (331 participants) to be able to say if routine surgery early on was of overall benefit. Further trials are needed and such trials should assess the pain that people suffer and their views of the disease and treatment.
This review examined the effectiveness of acupuncture for reducing pain in endometriosis; however only one study met our inclusion criteria. The data from the included study, involving 67 women, indicated that ear acupuncture is more effective compared to Chinese herbal medicine for reducing menstrual pain. The study did not report whether participants suffered any side effects from their treatments. Larger, well-designed studies comparing acupuncture with conventional therapies are necessary to confirm these results.
We searched the medical literature up to May 2015 for robust medical studies (randomised controlled studies) that compared NPWT with other treatments for pressure ulcers. We identified four studies involving a total of 149 participants. Two studies compared NPWT with dressings, one compared NPWT with a series of topical treatments and one study compared it with what was described only as 'moist wound healing'. The trials were small, and poorly described, of fairly short or unclear duration, and contained little in the way of useful data. As a result of the limited amount of research evidence available, we were not able to draw any conclusions regarding the potential value (or harm) of NPWT as a treatment for pressure ulcers. More, better quality research is needed if this is an important and relevant question for decision makers. This plain language summary is up-to-date as of May 2015.
This review included 19 trials (2137 participants). One trial compared laser trabeculoplasty associated with a hypotensive eyedrop with no intervention, and at six years of follow up the risk of visual field decay was greater in non treated participants. Three trials compared hypotensive eyedrops with trabeculoplasty, and the risk of uncontrolled IOP was greater at two years in the laser group. It is necessary to mention that the eyedrops used in these trials differ significantly from the ones used currently, since these trials were developed a decade ago. Three other trials compared trabeculoplasty with trabeculectomy and the risk of uncontrolled IOP was higher in the laser group at six months of follow up. There is some evidence showing that diode laser and selective trabeculoplasty have similar effect in controlling IOP when compared to argon laser trabeculoplasty. Comparisons of different lasers and different techniques of application were done in the remaining trials, but there is still not enough evidence to determine which is the best treatment protocol. Further research is necessary to compare trabeculoplasty with new hypotensive eyedrops and also the results of laser therapy in people of different ethnicities, since some studies suggest that they have a different response to this kind of laser therapy. More research is required to analyse cost-effectiveness of these interventions.
This review aimed to explore this question and included three studies with a total of 466 participants. These studies did not find any overall difference between asthma clinic and usual clinical practice care by a general practitioner for the following outcomes: A&E department visits for asthma, use of reliever or preventer medication for asthma and quality of life measures, but there was considerable uncertainty about these results. One study found that there was a reduction in nocturnal awakening due to asthma in the asthma clinic group compared to control but no difference in other symptom outcomes reported. Given the limited evidence found in this review, we believe that there is a need for further evidence in order to assess the effectiveness of asthma clinics.
We included studies that compared ICS with no ICS, or with a placebo (i.e. a medication made to look the same as ICS but with no active ingredients). We only included studies where it was decided at random who would receive ICS and who would not. The participants included in the seven studies were 380 adults who had bronchiectasis diagnosed by symptoms or from a detailed lung scan (computed tomography (CT)). We did not include studies that involved participants with cystic fibrosis, which can also cause bronchiectasis. Although we planned to include studies involving children with bronchiectasis, we did not find such studies. From available evidence up to June 2017, we found seven eligible studies involving adult participants that examined the role of ICS in bronchiectasis. The adults had stable bronchiectasis - they were not having a flare-up at the start of the study. We were able to include results from two studies that gave ICS for less than six months to adults with stable bronchiectasis. ICS did not make a difference to lung function, number of exacerbations during the study or quality of life. In a different study, which also gave ICS for less than six months, we found a small reduction in sputum (phlegm) and improvement in breathlessness. However, as these results were from a study which did not use a placebo we cannot be certain about them. The single study on long-term use of ICS (i.e. for over 6 months) showed no meaningful benefit of ICS for any of the outcomes. There were no studies conducted when the participants were having a flare-up of their bronchiectasis. There were also no studies that involved children with bronchiectasis. Importantly, we do not know if ICS are linked to more unwanted side effects, because the studies did not provide much information about this. The review found that there is not enough evidence for the routine use of ICS in adults with stable bronchiectasis. We can make no conclusions about the use of ICS for flare-ups of bronchiectasis, or about their use in children, because we did not find any studies. Overall, we judged the quality of evidence to be low. We were concerned because the largest study, which showed some benefits, did not use a placebo. This means that participants and staff in the study would have known who was getting ICS and who was not, which could affect the results. Also, our confidence was reduced because we only found a small number of studies to include in our review and some of the studies may have included people with other types of lung disease, in addition to bronchiectasis.
In May 2015, this review identified 28 small, low quality studies involving 2564 participants looking at intra-articular morphine for pain relief after knee arthroscopy. From 9/20 studies we did not find evidence that intra-articular morphine given at a dose of 1 mg was better than placebo for pain relief. From the limited evidence available we were unable to determine how intra-articular morphine compared with morphine injected into the muscle (intra-muscular morphine). There was also low quality evidence for the effects of 1 mg intra-articular morphine compared with intra-articular bupivacaine, non-steroidal anti-inflammatory drugs (NSAIDs), sufentanil, fentanyl and pethidine, so we were unsure which worked best. We were unable to determine how similar the rates of side effects such as nausea and vomiting were between intra-articular morphine and placebo. Overall, the quality of the evidence was low. Future research should focus on finding effective analgesics for knee arthroscopy.
One trial compared pramipexole with bromocriptine but this was not designed to examine differences between the two treatments as there were too few patients included. However, there was a larger reduction in the time patients spent in the immobile off state with pramipexole therapy compared with bromocriptine by an average of 1.4 hours. No differences occurred in dyskinesia rating scale, dyskinesia as a side effect or Unified Parkinson's Disease Rating Scale (UPDRS) complication score. The UPDRS activities of daily living and motor scores showed similar improvements compared to placebo with both agonists. Levodopa dose reduction was similar with both agonists. Subscales of a quality of life measure, the Functional Status Questionnaire, showed significant improvements compared to placebo with both agonists. The finding that another quality of life scale, the EuroQol, improved significantly compared with placebo with pramipexole but not bromocriptine should be treated with caution. Side effects such as nausea, vomiting, and faintness were similar with each agonist, as was the withdrawal from treatment rate. No conclusions regarding the comparative effectiveness and safety of pramipexole versus bromocriptine can be drawn as this single trial did not have adequate numbers of patients to assess such differences. Further larger trials are required to examine this issue in the future.
This review found that OA should not be considered as first choice therapy for OSAH, where symptoms and sleep disruption are severe. There has not been a sufficient amount of research that examines the effects of OA compared with CPAP in terms of symptoms and quality of life. Although CPAP was clearly more effective at reducing the disruption to sleep, some people with OSAH may prefer using them if they are found to be tolerable and more convenient than CPAP. When an active OA was compared with an inactive OA , there were improvements in daytime sleepiness and apnoea/hypopnoea severity. OA may be more effective than corrective upper airway surgery. Further research should consider whether people with more distinctly severe symptoms respond in a similar way to those patients represented in the studies we have included in the review.
We found 39 studies including more than 16,000 adults and children with asthma who were taking a steroid inhaler. Most studies collected data at six months, so we can really apply the messages in this review only over six months - we cannot say whether these methods are effective in a few years time, for example. We searched multiple sources for relevant studies. This review is current as of November 2016. Different studies tried different ways to help people take their inhaler more regularly. We grouped studies according to four ways of helping people take their inhaler: providing education about adherence (20 studies); using electronic monitoring or reminders to take the inhaler (11 studies); making the drug easier to take (e.g. once instead of twice a day, one inhaler instead of two) (four studies); and giving the inhaler during school hours (three studies). We mainly looked for whether strategies helped people to take their inhaler as prescribed, and whether people had fewer asthma attacks and better asthma control. People who were given education were better at taking their inhaler than controls; 20% more people took their treatment (likely to be somewhere between 8% and 33% more). Those given trackers or electronic reminders were 19% better at using their inhaler than controls (14% and 25%). People who were given an easier way of taking their inhaler (e.g. fewer times a day) were only 4% better than those who carried on as usual (2% and 6%). Unfortunately, these efforts to help people take their inhaler as prescribed generally did not lead to obvious benefit for things like asthma control and number of attacks, but in most cases, we could not tell either way. We also did not see a difference for quality of life or time people needed off school or work, but the evidence was often uncertain. Studies investigating the possible benefit of giving children their inhaler during school hours did not actually measure how often they missed doses. It's difficult to tell whether these different strategies are worth using because studies were quite different from one other. This variation means that we cannot be sure what the real benefit is, beyond improving adherence. Sometimes we did not find enough studies to detect a difference between groups. The fact that most people knew which group they were in also reduced our confidence in the findings because this can affect things like how positively people respond to questionnaires. We had concerns about how many people dropped out of about half the studies, and we are uncertain whether studies reported everything they measured. The studies we found suggest that various strategies can help people with asthma take their inhaler better, compared with "control" (e.g. usual asthma care). However, many of these studies were quite different from one another, and we are not certain about whether people will find that their asthma is improved as a result of this approach.
Both studies in this review took place in the USA and were aimed at uninsured children. In the first study, case managers contacted the families of uninsured Latin American children, gave them information about health insurance, helped them apply, and helped them appeal when a wrong decision was made. In the second study, insurance application forms were handed out to the families of children visiting hospital emergency departments. In both studies, these families were compared to families who were not given additional information or support. The studies showed the following: People who are offered health insurance information and application support: - are probably more likely to enrol their children into health insurance programmes (moderate quality evidence); - are probably more likely to continue insuring their children (moderate quality evidence); - may be quicker at getting insurance (low quality evidence); - may be more satisfied with the process of enrolment (low quality evidence). People who are given insurance application forms in the emergency departments of hospitals: - may be more likely to enrol their children into health insurance programmes (low quality evidence). No unwanted effects were reported in the studies. A possible unwanted effect might be that people could experience the information and support as annoying or unhelpful. However, in the one study that measured the parents’ satisfaction, people were more satisfied when given information and support. A summary of this review for policy-makers is availablehere
High withdrawal rates from the trials limit the confidence that can be placed on the results. Olanzapine was superior to placebo in reduction of manic symptoms both as monotherapy and combined with mood stabilizers, though caused weight gain. Olanzapine was more efficacious than divalproex and caused less nausea but more weight gain, somnolence and movement disorders. Olanzapine was comparable to haloperidol in efficacy, caused less movement disorders but greater weight gain.
We found 29 papers on the impact of conditional cash transfers (CCT) on access to care and health outcomes. Of these, ten papers, reporting results from six studies, satisfied the inclusion criteria; four of these studies were randomised experiments. Despite a number of methodological weaknesses in some studies, overall the research evidence suggests that CCT schemes may result in a number of benefits to health for poor populations. Many conditional cash transfer programmes include a number of components, including incentivising attendance for health education, measurements of height and weight, immunisations and nutritional supplementation. Conditional cash transfer programmes appear to be an effective way to increase the uptake of preventive services and encourage some preventive behaviours. In some cases programmes have noted improvement of health outcomes, though it is unclear to which components this positive effect should be attributed.
This review investigated the effectiveness of any kind of psychological treatment conducted by paraprofessionals.The few studies found did not allow conclusions about the effect of paraprofessionals compared to professionals in the treatment of anxiety and depressive disorders. Pooling data from three studies, involving women only, indicated a significant effect for paraprofessionals compared to no treatment. The evidence so far may justify the development and evaluation of programs incorporating paraprofessionals in treatment programs for anxiety and depressive disorders.
We included six studies with a total of 3284 participants with ARIs from primary care settings (point-of care test: C-reactive protein). Two of the included studies received direct financial support from manufacturers. The evidence is current to January 2014. The only point-of-care biomarker of infection currently available to primary care identified in the review was C-reactive protein. A reduction in antibiotic use is likely to be achieved by a C-reactive protein point-of-care test but due to differences in the designs of the included studies, it was not possible to obtain a precise effect estimate of the reduction. There were no deaths in the studies and we did not find evidence suggesting that time to recovery from ARIs and their duration were longer, nor that levels of patient satisfaction or number of re-consultations were affected in the C-reactive protein group. However, a possible increase in the risk of hospital admission cannot be ruled out. We ranked the evidence as of moderate quality according to the GRADE levels due to an imprecise effect estimation. Used as an adjunct to a doctor's clinical examination point-of-care tests (e.g. C-reactive protein) can reduce antibiotic use in ARIs in general practice. The possibility of an increased risk of hospital admission suggests that care must be taken in how these tests are used. A more precise effect estimate is needed to assess the costs of the intervention and compare the use of a point-of-care biomarker to other antibiotic-saving strategies.
We included 83 studies (in particular randomised controlled trials) of evidence-based psychotherapy interventions (cognitive behavioural therapy (CBT) and third wave CBT, interpersonal therapy) that had the specific aim of preventing the onset of depressive disorder. For the primary outcome of depression diagnosis at medium-term follow-up (up to 12 months), there were 32 trials with 5965 participants and for the primary outcome of depression symptoms (self-rated) there were 73 trials with 13,829 participants. What does the evidence from the review tell us? We found that, compared with any comparison group, psychological depression prevention programmes have small positive benefits on depression prevention. There were some problems with the way the trials were done and in particular the results showed that compared to an attention placebo comparison group (a control intervention that controls for non-specific factors like involvement in a trial and attention from researchers), these programmes had no effect. There is still not enough evidence to support the implementation of depression prevention programmes. However, based on the effects seen for targeted depression prevention programmes (albeit with inadequate control groups), we recommend that further research be undertaken to test the effectiveness of depression prevention programmes in populations of young people who already have some symptoms of depression. Such trials should compare the intervention to an attention placebo comparison group and measure whether depressive diagnosis is prevented in the long term. They also need to consider whether the approach is something that can be implemented in the real world. In addition, they should consider and measure whether the intervention produces harmful outcomes.
We searched to literature up to January 2016 and found three studies (reported in 5 publications that involved 179 participants) that compared these two types of kidney donor surgeries. LESS-DN was found to be as safe as standard keyhole surgical techniques; pain at discharge was significantly less with LESS-DN, however there were no other discernible benefits over the standard technique. Overall, we found there was a low risk of bias for all studies; however, funding sources were not reported in two or three studies, and there was high risk of attrition bias in one study. The small number of studies with few participants eligible for inclusion indicates a need for future research in this area.
For this systematic review, the authors searched for randomised controlled trials which investigated the effects of caffeine on injury, error and cognitive performance in shift workers. They found 13 trials - none of the trials looked at the effect on injury, two trials measured error, while the remaining trials used neuropsychological tests to assess cognitive performance. The results of the trials suggest that compared to no intervention, caffeine can reduce the number of errors and improve cognitive performance in shift workers. No difference in effect was found by the trials comparing caffeine with other interventions (such as nap, bright light and modafinil). However, due to some methodological weaknesses of the trials, some caution is required when interpreting the results. The authors of the systematic review conclude that caffeine may be an effective intervention for improving performance in shift workers however, there are no trials from which they could assess its effect on injuries. Based on the current evidence, the review authors judge that there is no reason for healthy shift workers who already use caffeine within recommended levels to improve their alertness, to stop doing so. They go on to suggest that it would be useful for further trials to be undertaken to assess the effects of caffeine against other potential countermeasures.
We examined evidence from 182 included studies reporting the experience of 16,855 people of all ages. The evidence is current to March 2019. In total, 10,696 people (64% of the total who had surgery in all studies) experienced a good outcome from surgery, defined as freedom from epileptic seizures. Two randomised controlled trials (RCTs) established the superiority of surgery over use of different antiepileptic medications. Seven RCTs compared different types of surgery. Three trials found no difference in seizure outcomes; one removed 2.5cm or 3.5cm of the anterior temporal lobe (ATL - the part of the brain in which the epileptogenic zone is often located) or surgically removed the ATL with or without an additional procedure to sever the nerves that connect the two halves of the brain. The third trial found that completely removing the hippocampus (the part of the brain in which the epileptogenic zone is often located) was superior to removing only part of the hippocampus. A fourth trial showed that removing the ATL was superior to a surgical procedure using radiation therapy, Two trials showed no difference between different types of surgical procedures to remove the ATL or hippocampus and the final trial showed that for Lennox-Gastaut syndrome, results show no significant differences in seizure outcomes between those undergoing resection of the epileptogenic zone and those with resection plus corpus callosotomy. We identified some factors associated with a better outcome from surgery, including a well-defined abnormality on the MRI scan corresponding with what was expected from the description of seizures and EEG findings, complete surgical removal of the lesion, and a history of febrile seizures (seizures associated with fever in a young child) often associated with mesial temporal sclerosis (scarring in the inner portions of the temporal lobe of the brain). More spread out brain abnormalities that might be associated with brain injury or an abnormality of brain development were not associated with a good outcome. The presence of such abnormalities is often associated with a need to embark on more detailed pre-operative investigations including intracranial (inside the skull) EEG monitoring. We would have liked to examine the collective effect of these factors (i.e. the effect on outcome if a person has a history of febrile seizures, brain injury, and an MRI abnormality altogether); however, studies did not report enough information to allow this. Most studies included in this review were of poor quality and had a retrospective design (whereby individuals are recruited after the result of surgery has been recorded, which looks back for the existence of factors related to the results of surgery). Researchers used variable surgical approaches for different sites of the brain, different processes to select candidates for surgery, and different definitions of freedom from seizures after surgery, and they measured these outcomes at varying points. Fewer than half the studies gave details of complications and deaths associated with surgery. We encourage researchers that future studies should have a prospective design (a design whereby individuals are recruited before surgery has taken place, which identifies factors of interest before surgery and follows up with individuals after surgery to record outcomes). Studies should use appropriate statistical methods to examine the collective effect of factors that may predict the outcome of surgery. Study authors should clearly record death during or after surgery, as well as complications and side effects from surgery.
In this review we found four studies with a total of 224 participants that were suitable for inclusion; one was performed exclusively in children and three in adolescents or adults. However, data could only be obtained from two studies; both studies used mucolytics (ambroxol and bromhexine) in conjunction with antibiotics. Combining these two studies, the rate of cure or improvement in cough of people who received mucolytics was similar to those who did not. However, in the secondary analysis, children who received a mucolytic were more likely to be cured of cough (the number needed to treat to benefit (NNTB) at day 10 was 5 for children and 4 for adults). There were no reported increased adverse events in the treatment group. The range of possible adverse events associated with OTC medications for cough is wide and includes minimal adverse events (such as with the use of honey) to serious adverse events, such as altered heart rate patterns, drowsiness and death in young children. The studies included in this review did not report any detectable increase in adverse events. There were no obvious biases in the studies. This review has substantial limitations due to the unavailability of data from studies. Also there are no studies of other common OTC medications used for cough, such as antihistamines and antitussives. Thus, there is insufficient evidence to draw any definitive conclusions on the role of OTC medications taken as an additional treatment for cough associated with acute pneumonia. Mucolytics may be beneficial but the lack of consistent evidence precludes recommending the routine use of mucolytics as an addition in the treatment of troublesome cough associated with pneumonia in children or adults. The evidence is current to January 2014.
We searched the literature on 20 Janurary 2015 and found 19 relevant studies with a total of 1421 patients that compared different types of buprenorphine to each other or to other strong pain relief medicines or to placebo. The reported average ages of the patients ranged from 49.1 years to 67.16 years, and the duration of the studies ranged from single dose treatment to six months. Generally, the studies showed that buprenorphine is an effective strong pain relief medicine that in some cases may be slightly better than other strong pain relief medicines. However, the evidence provided by these studies were of very low quality and on the basis of the available evidence, it is still hard to say where buprenorphine fits in in the treatment of cancer pain with strong opioids. All the strong pain relief medicines examined in the studies are also associated with a number of unwanted effects, such as vomiting, constipation and drowsiness.
We included 17 studies that had a total of 1988 participants (evidence current until November 2017). These studies used various types of gene therapy as well as different dosages, some providing single treatments and some repeated treatments. Most of the studies included people with critical limb ischaemia; three studies included people with intermittent claudication. When combining the data, we found no clear differences between people who received gene therapy and those who did not in terms of amputation-free survival (patients who did not have an amputation and did not die), major amputation (above the ankle), or death. We did see improvement in complete ulcer healing in the gene therapy treatment group compared to the control group. Studies show no clear differences in pain symptom scores, but we evaluated only two studies for this outcome. Not enough data are available to show if there was a difference between groups for the measure of blood flow known as the 'ankle brachial index'. We were not able to combine data on quality of life or pain-free walking distances (distances one can walk without experiencing leg pain). Risk of bias of the included studies varied greatly, and this was a concern because studies did not clearly report on their methods nor on follow-up of participants. Most studies used a placebo control, which increases the risk that outcomes may have been different if people knew they were given treatment or control. Corporations that produce the tested treatments sponsored all included trials. The quality of evidence varied from moderate to very low. For amputation-free survival, major amputation, and death, we considered the quality of evidence to be moderate because of differences between studies. For ulcer healing, risk of bias was a matter of concern, and study results were imprecise because few events were reported. The quality of evidence for quality of life was very low because of differences between studies and insufficient information to combine study findings. The quality of evidence for the ankle brachial index was low because only one study with few participants reported this outcome. For pain symptom scores, the quality of evidence was very low because of technical problems within one of the two studies, as well as differences between the two studies and few participants.
In the 12 controlled studies identified, laparoscopic surgery was associated with reduced risk of any adverse events from surgery, less pain, and fewer days in the hospital when compared to laparotomy, the traditional surgical technique.There was no difference between the procedures with regard to outcomes of fever, postoperative infections, and tumour recurrence.
The authors of this review tried to assess whether changes in dietary habits could favourably influence the prognosis for people with MS. Although a massive amount of data has been published in this area, only six controlled studies on PUFA, comprising a total of 794 patients, met the inclusion criteria in terms of methodological quality for this review. No studies on vitamins and antioxidant supplements were found that met our criteria. No papers on any other proposed dietary interventions for MS were found after extensive searching of the scientific databases.  The available data are insufficient to assess any potential benefit or harm that might result from PUFA supplementation. The absence of evidence on PUFA and the extensive lack of data on other supplements is an unfortunate event since 50% to 75% of people with MS do use dietary regimens and supplements.
The review of trials found that some of the Chinese medicinal herbs may have a positive effect on the clearance of hepatitis B virus and on the diseased liver. However, the methodological quality of the trials evaluating these herbs was generally poor. Analysis of the identified trials also indicated that trials with positive findings are more likely to be published than trials without significant findings. Further, medicinal herbs may be associated with side effects. Therefore, Chinese medicinal herbs should not be used outside new trials. Testing the herbs in larger, well-designed trials is needed in order to establish the necessary evidence for their use.
Exercise training using vibratory platform (whole body vibration) has been recently introduced as a complementary treatment to rehabilitation.This review identified ten trials performing whole body vibration (WBV) in neurodegenerative diseases: six in Parkinson's disease and four in multiple sclerosis. Diversity in treatments and outcomes measures makes difficult to quantitatively compare the effect of WBV intervention across studies and to assess its efficacy. There is insufficient evidence to determine the potential benefits of WBV training in functional performance according to activities of daily life, body balance, signs and symptoms of disease, muscle performance, and quality of life in patients with neurodegenerative diseases. Adverse events were poorly reported in the included studies, but this kind of training seems to be a safe intervention. These conclusions are based on a small number of studies with a limited methodological quality.
This review assessed the effect of hormone replacement on treatment of osteoporosis in women with primary biliary cirrhosis. We found no evidence of effect of hormone replacement on mortality and fractures in women with primary biliary cirrhosis. It seems that hormone replacement given to women with primary biliary cirrhosis is connected with a significant increase in the occurrence of adverse events compared with placebo or no intervention. Hormone replacement appears to have no effect on the lumbar bone mineral density compared with placebo or no intervention. Hormone replacement may decrease bone mineral density measured at the proximal femur. We did not find evidence to support the use of hormone replacement for osteoporosis in women with primary biliary cirrhosis.
A systematic literature search was conducted to find studies on interventions to reduce occupational injuries in agriculture. Eight studies were found from over 8600 references. The quality of the relevant studies was assessed and their results extracted. Randomised controlled trial data were combined across studies in a meta-analysis. Interrupted time series studies were reanalysed to assess if there was a change in the level or trend of injuries associated with the intervention. Five randomised controlled trials with 11,565 participants and one interrupted time series study with 14 measurement points used combinations of various educational interventions and financial incentives. Two of these studies concentrated on injury prevention among children or adolescents and the rest dealt with injury prevention among adults. The effect of legislation was evaluated in two interrupted time series studies with on average 32.5 measurement points. One study evaluated regulations to prevent tractor rollover injuries in Sweden and another study evaluated regulation to reduce fatal pesticide poisonings in Sri Lanka. The methodological quality was rated as less than high for all included studies. The studies provided no evidence that the educational interventions had an injury reducing effect. However, insurance premium discounts as a financial incentive decreased injuries claims in one study. Specific legislative mandates expanding the use of Rollover Protective Structures (ROPS) on tractors were not associated with a reduction of injuries in one study. Legislation to ban Endosulfan pesticides was associated with a reduction in fatal poisonings in the long term in another study.
This update found no new eligible trials. The original review found three trials investigating the effects of red blood cell transfusion in patients with upper gastrointestinal tract bleeding. There were more deaths recorded in the transfusion arm of the combined studies compared to the control arm. It is by no means clear that transfusion is a surrogate marker for more severe haemorrhage. The deaths were too few and the trials too disparate to draw any firm conclusions regarding the effects of transfusion on mortality. We can only recommend that further, larger studies are done.
This review found only one eligible clinical trial which compared different designs of these products and had been carried out in the last ten years. This trial included all the designs. There is evidence that for leakage prevention, overall acceptability and preference, disposable inserts are better than menstrual pads, which are better than washable pants with integral pad, which are better than washable inserts. There is no clear benefit for skin health using either washable or disposable designs. Most women preferred the disposable insert pad but some preferred the other cheaper designs or would find them acceptable in some situations. Allowing women to choose their preferred design of absorbent product (or combination of different designs for different circumstances) would be more cost-effective and provide better patient satisfaction than provision of disposable insert pads alone.
We found three trials involving 104 people (75 children and 29 adults) with acute asthma. There was no significant difference in adults receiving intravenous beta-agonists as well as standard care in the one small trial considering this comparison. We also looked at length of stay in the emergency department. Two reported shorter recovery time or quicker discharge from the emergency department in patients also receiving intravenous beta-agonists. One trial reported that more children experienced tremor if they had received injected beta-agonists whereas another trial, with adults, reported no significant difference in adverse effects. As there are so few trials and so few included patients we cannot be sure about the reliability of these findings. This review found that until more, larger, high quality clinical trials in this area are conducted it is not possible to judge whether there is any enhanced benefit using additional intravenous beta2-agonists in children or adults with severe acute asthma compared with inhaled beta2-agonists alone.
For research published up to April 2015, there were 105 studies involving 31,043 people. The decision aids focused on 50 different decisions. The common decisions were about: surgery, screening (e.g. prostate cancer, colon cancer, prenatal), genetic testing, and medication treatments (e.g. diabetes, atrial fibrillation).The decision aids were compared to usual care that may have included general information or no intervention. In the 105 studies, 89 evaluated a patient decision aid used by people in preparation for the visit with the clinician, and 16 evaluated its use during the visit with the clinician. When people use decision aids, they improve their knowledge of the options (high-quality evidence) and feel better informed and more clear about what matters most to them (high-quality evidence). They probably have more accurate expectations of benefits and harms of options (moderate-quality evidence) and probably participate more in decision making (moderate-quality evidence). People who use decision aids may achieve decisions that are consistent with their informed values (evidence is not as strong; more research could change results). People and their clinicians were more likely to talk about the decision when using a decision aid. Decision aids have a variable effect on the option chosen, depending on the choice being considered. Decision aids do not worsen health outcomes, and people using them are not less satisfied. More research is needed to assess if people continue with the option they chose and also to assess what impact decision aids have on healthcare systems.
We included six studies with 2469 participants with COPD, and a further five studies with 4281 older or high risk participants, a proportion of whom had chronic lung disease. We found some moderate-quality evidence that inactivated influenza vaccine did decrease 'flare ups' of COPD, especially those that are related to the influenza virus itself. The inactivated influenza virus vaccine was given as an injection in the muscle, and was associated with an increase in local side effects (such as pain) at the site of injection, which were short-lived. The inactivated virus vaccine did not cause influenza, or any significant worsening of COPD. Adding a live attenuated virus to the inactivated virus did not add any further protection for the participants. The evidence was of moderate quality. There have been no new trials since 2004. We conducted the last literature search in December 2017.
Data were collected from two randomised studies (involving 319 women) which compared women with epidurals who were given either oxytocin, or a placebo. The rates of operative deliveries were not clearly different between the two groups There were also no significant differences between the other outcomes analysed, such as the Apgar scores of the newborn babies, admissions to the neonatal nursery, rates of post birth haemorrhage or rates of over stimulation of the uterus. Both studies appeared to have a low risk of bias. Overall, there was no significant difference between the rates of operative deliveries in women with epidurals who were given oxytocin compared with those who received the placebo. However, as there were limited data available, in order to fully determine whether augmentation of women with epidurals reduces the rate of operative deliveries and therefore reduces the complications associated, further studies are required.
We searched for trials which compared a polysaccharide or conjugate pneumococcal vaccine schedule with a different schedule or no vaccination in people with sickle cell disease. The review includes five trials with a total of 547 participants. One trial showed that the polysaccharide vaccine did not reduce the risk of infection very much in children younger than three years old, but it was linked with only minor adverse events. Three trials of conjugate vaccines showed increased antibody responses compared to control groups in people of all ages, although clinical outcomes were not measured in these trials. This review did not show if the vaccines prevent infection or decrease death rates. We recommend that conjugate pneumococcal vaccines are used in people with sickle cell disease. Randomised trials will be needed to determine the best vaccination schedule when further, potentially more effective vaccines become available. Such trials should measure clinical outcomes of effectiveness.
Study characteristics: We included five studies that compared surgical versus non-surgical treatment in a total of 643 people with lumbar spinal stenosis. Average age of participants in all studies was over 59 years. Follow-up periods ranged from six weeks to 10 years. Key results: We cannot conclude on the basis of this review whether surgical or non-surgical treatment is better for individuals with lumbar spinal stenosis. Nevertheless, we can report on the high rate of effects reported in three of five surgical groups, ranging from 10% to 24%. No side effects were reported for any of the conservative treatment options. Three studies compared spine surgery versus various types of non-surgical treatment. It is difficult for review authors to draw conclusions from these studies because non-surgical treatments were inadequately described. One study that compared surgery versus bracing and exercise found no differences in pain. Another study compared surgery versus spinal injections and found better physical function with injections, and better pain relief with surgery at six weeks. Still another trial compared surgery with an implanted device versus non-surgical care. This study reported favourable outcomes of surgery for symptoms and physical function. Quality of the evidence: Evidence obtained by comparing surgery versus non-surgical treatment is of low quality. Well-designed studies are needed to examine this problem. In particular, researchers need to do a better job of describing the details of non-surgical treatments.
This update included 33 randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) involving 7296 participants. Treatments included rivaroxaban (a medicine called a direct oral inhibitor of activated factor X), injections of medicines under the skin to prevent blood clotting (e.g. fondaparinux, low molecular weight heparin, or unfractionated heparin), elastic compression stockings, oral non-steroidal anti-inflammatory drugs (NSAIDs; a pain killer medicine), topical treatment (medicine applied to the skin), and surgery. One large study, accounting for half of the participants included in the review, showed that treatment with fondaparinux for 45 days was associated with a significant reduction in symptomatic VTE (where symptoms indicate there is a VTE), ST extension (where the clot moves further up the leg), and recurrence of ST (where clots return) compared to placebo. Major bleeding was infrequent in both groups. In one study in people with ST at high risk of recurrent thromboembolic events, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban. There were no major bleeding events in either group. Both low molecular weight heparin and NSAIDs reduced the occurrence of extension or recurrence of ST with no effect on symptomatic VTE or major bleeding. Topical treatments relieved local symptoms but the trials did not report on progression to VTE. Surgical treatment and wearing elastic stockings were associated with a lower rate of VTE and progression of the ST compared with elastic stockings alone. Overall, the quality of evidence was very low for most treatments due to poor study design, imprecision of results, lack of a placebo (non-treated) group and only one study in some comparison. The quality of evidence was low to moderate for comparisons in two placebo-controlled trials. In conclusion, fondaparinux appears to be an adequate treatment for most people with ST. The optimal dose and duration of treatment need to be established in people at high risk as well as people at low risk for recurrent thrombotic events. Further research is needed to assess the role of rivaroxaban and other such medicines, or thrombin, low molecular weight heparin or NSAIDs and to demonstrate the effectiveness, if any, of topical treatment, or surgery in terms of VTE.
We found that music therapy plus treatment as usual is more effective than treatment as usual alone. Music therapy seems to reduce depressive symptoms and anxiety and helps to improve functioning (e.g. maintaining involvement in job, activities, and relationships). We are not sure whether music therapy is better than psychological therapy. We do not know whether one form of music therapy is better than another. The small numbers of identified studies and participants make it hard to be confident about these comparisons. Music therapy for depression is likely to be effective for people in decreasing symptoms of depression and anxiety. Music therapy also helps people to function in their everyday life. However, our findings are not complete and need to be clarified through additional research. Future trials should study depression in children and adolescents, and future trial reports should thoroughly describe music therapy interventions, other interventions, and the person who delivers these interventions.
We looked for evidence from randomised controlled trials that investigated TPD versus other forms of dialysis for people with AKI. Only one study of enrolling 87 participants was found that compared TPD with continuous equilibrating PD (CEPD). This study showed that TPD produced higher solute clearances in less time with greater protein loss than CEPD, but did not report how well patients recovered kidney function, nor if any people died. There was insufficient evidence to determine if TPD is better or worse than other types of PD for patients with AKI.
To test the efficacy we measured the disability changes and the proportion of patients who had new relapses, while to test the safety we took into account the number of patients who exhibited any type of adverse events. We searched scientific databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment group) comparing daclizumab, alone or with other treatments versus placebo (a pretend treatment). Patients were aged 18 to 65 years with relapsing remitting multiple sclerosis. Evidence is current to May 2013. We found two studies (funded by Facet Biotech/Biogen Idec and Biogen Idec/AbbVie Biotherapeutics Inc), which met our inclusion criteria, with 851 patients, both male and female, aged 18 to 65 years. The results did not provide sufficient evidence on the effectiveness of daclizumab, and further studies are needed. One study is still ongoing. Daclizumab was generally well-tolerated, the most frequent adverse events being infections, which were all resolved with standard therapies. In order to have more clear results, the length of follow-up (where the patients are observed and monitored following treatment) needs to be longer. We considered both studies to be of high quality.
The evidence is current to April 2015. The review included two studies, one each from Australia (750 participants) and Norway (61 participants). In both studies, half of the participants received a reablement-based home-care package and half usual home-care provision. The very low quality evidence for all of the results means that we are uncertain about the effects of reablement when compared with usual care. Reablement may help some older adults to improve their abilities to engage in everyday activities (functional status) to a small degree, but may make little or no difference to death rates or admissions to hospital. The findings mean we are also uncertain whether reablement affects quality of life or living arrangements. Reablement may lead to a small decrease in numbers of people needing higher levels of personal care, and may decrease care costs to a small degree, but neither study reported satisfaction of those using the reablement service. While there may be some small positive effects of reablement, the evidence was very low quality, meaning that we are very uncertain about how large or important these effects may be. There is a need for more studies to be conducted in a range of countries and situations before the effectiveness and safety of reablement can be determined with certainty.
This review found four small studies that evaluated the effect of steroids on low blood pressure in premature infants. At present, there is insufficient information on which to base recommendations about the value of giving steroids to babies born before term who have low blood pressure.
We conducted a review of seven randomised controlled trials (1684 participants) comparing nurse titration of beta-adrenergic blocking agents, ACEIs, and ARBs with titration of these medications by a primary care physician. The demographic characteristics of participants within each study were similar. There was an equal number of men and women in four of the studies. The mean age of participants ranged from 59 to 81 years of age. The evidence is current up to December 2014. The review found that participants undergoing titration of these medications were less likely to experience a hospital admission or to die, and more participants reached the maximum dose compared to those participants having these medications titrated by their primary care physician. Approximately 27 deaths could be avoided for every 1000 patients undergoing titration of these medications by nurses under medical supervision or nurse practitioners. There was very little reported data on the titration of ACEIs and ARBs. Two studies reported on adverse events; one of these studies stated there were no adverse events, and the other study found one adverse event but did not specify the type or severity of the adverse event. In conclusion, titration of these medications by nurses under medical supervision or nurse practitioners may improve their up-titration, which may result in an improvement in patient outcomes. We rated the quality of evidence regarding the proportion of participants that reached optimal dose of these medications as low. This indicates uncertainty as to whether the number of participants reaching optimal dose of beta-adrenergic blocking agents was different due to NLT or usual care. We found high-quality evidence that NLT reduced hospitalisations for any cause compared to usual care. This indicates that we are confident that the reduction in all-cause hospitalisations was due to NLT, and further research is unlikely to change this finding.
The objectives of this review was to assess the effects of HBC on morbidity and mortality in those with HIV/AIDS. A comprehensive search for clinical trials of HBC including all forms of treatment, care and support offered in the home was done. Eleven completed and two ongoing studies were identified. Studies were generally small and very few studies were done in developing countries. There was a lack of studies truly looking at the effect of home based care itself or looking at significant end points (death and progression to AIDS). Intensive home-based nursing significantly improved self-reported knowledge of HIV and medications, and self-reported adherence to medication. Another study, comparing proportion of participants with greater than 90% adherence, found statistically significant differences over time but no significant change in CD4 counts and viral loads. A third study found significant differences in HIV stigma, worry and physical functioning but no differences in depressive symptoms, mood, general health, and overall functioning. Comprehensive case management by trans-professional teams compared to usual care by primary care nurses had no significant difference in quality-of-life after 6-months of follow-up and average length of time on service. Home total parenteral nutrition had no significant impact on overall survival and rate of re-hospitalisation. Two trials comparing computers with brochures/nothing/standard medical care found no significant effect on health status, and decision-making confidence and skill, but a reduction in social isolation after controlling for depression. Two trials evaluating home exercise programmes found opposing results. Home-based safe water systems reduced diarrhea frequency and severity among persons with HIV in Africa.
This review includes 14 trials, randomizing a total of 8033 women, and showed that a policy of early routine augmentation for mild delays in labour progress resulted in a modest reduction of the caesarean section rate compared with expectant management. The reduction in caesarean sections was most evident in the 11 trials looking at prevention of abnormal progression, rather than therapy (three trials). In these women, the time from admission to giving birth was also reduced (mean difference 1.3 hours). The trials did not provide sufficient evidence on indicators of maternal or neonatal health, including women’s satisfaction and views on the experience. Documentation of other aspects of care, such as continuous professional support, mobility and positions during labour, was limited as was the degree of contrast between groups. Women in the control group also received oxytocin but often later than in the intervention group. The severity of delay which was sufficient to justify interventions remains to be defined.
We included three studies, published between 1996 and 2004 and conducted in the USA and the UK, including 270 eyes in analyses, comparing vitrectomy and observation after 6 or 12 months. The evidence is current as of March 2015. Vitrectomy improved visual acuity in participants with macular hole by about 1.5 lines of a standard distance acuity chart. Macular hole closure was much more likely with vitrectomy compared to observation, with mean closure rates of 76% versus 11%, respectively. Cataract surgery was common in operated eyes. In the largest study, retinal detachment occurred in the months following vitrectomy in about 5% of cases. The evidence was of moderate quality, as the visual acuity measurement was unmasked. Vitrectomy is effective in improving visual acuity, resulting in a moderate visual gain, and in achieving hole closure in people with macular hole. However, as vitrectomy technology has improved since the included trials were conducted, with use of a smaller incision and outpatient care, the results of this review may not apply to modern surgery.
In September 2016 we searched for randomised controlled trials (RCTs) involving nasal decontamination for preventing SSI. We included two studies with 291 participants, all adults undergoing cardiac surgery. The anti-bacterial products used for cleaning the nose were mupirocin (antibiotic cream) and Anerdian (disinfectant solution). It is unclear whether nasal decontamination makes a difference to the rate of SSI in people carrying S aureus bacteria. S aureus SSI was reported in only one trial and the results do not allow us to be certain about differences in infection rates. Some participants in the Anerdian study reported side effects such as itching around the nose, but these were not serious. Mortality was low where reported (one death was directly related to S aureus infection). The two studies we found did not have many participants and the results were inconclusive. The Anerdian study report did not provide information about how the trial was conducted and this makes it difficult to be sure if it was at risk of bias. The mupirocin study was of better quality and at low risk of bias; but the small number of participants and limited effects affect the quality of the results. Evidence of the potential benefits and harms of using nasal decontamination for the prevention of SSI is currently of low to very low certainty. Larger, better-reported RCTs are needed to assess the clinical effectiveness of this treatment. This plain language summary is up to date as of September 2016.
This Cochrane Review summarizes trials evaluating different interventions to improve water quality and prevent diarrhoea. After searching for relevant trials up to 11 November 2014, we included 55 studies enrolling over 84,000 participants. Most included studies were conducted in low- or middle-income countries (LMICs) (50 studies), with unimproved water sources (30 studies), and unimproved or unclear sanitation (34 studies). What causes diarrhoea and what water quality interventions might prevent diarrhoea? Diarrhoea is a major cause of death and disease, especially among young children in low-income countries where the most common causes are faecally contaminated water and food, or poor hygiene practices. In remote and low-income settings, source-based water quality improvement may include providing protected groundwater (springs, wells, and bore holes) or harvested rainwater as an alternative to surface sources (rivers and lakes). Alternatively water may be treated at the point-of-use in people's homes by boiling, chlorination, flocculation, filtration, or solar disinfection. These point-of-use interventions have the potential to overcome both contaminated sources and recontamination of safe water in the home. What the research says There is currently insufficient evidence to know if source-based improvements in water supplies, such as protected wells and communal tap stands or treatment of communal supplies, consistently reduce diarrhoea in low-income settings (very low quality evidence). We found no trials evaluating reliable piped-in water supplies to people's homes. On average, distributing disinfection products for use in the home may reduce diarrhoea by around one quarter in the case of chlorine products (low quality evidence), and around a third in the case of flocculation and disinfection sachets (moderate quality evidence). Water filtration at home probably reduces diarrhoea by around a half (moderate quality evidence), and effects were consistently seen with ceramic filters (moderate quality evidence), biosand systems (moderate quality evidence) and LifeStraw® filters (low quality evidence). Plumbed-in filtration has only been evaluated in high-income settings (low quality evidence). In low-income settings, distributing plastic bottles with instructions to leave filled bottles in direct sunlight for at least six hours before drinking probably reduces diarrhoea by around a third (moderate quality evidence). Research assessing the effects of household connections and chlorination at the point of delivery will help improve our knowledge base. Evidence indicates the more people use the various interventions for improving water quality, the larger the effects, so research into practical approaches to increase coverage and help assure long term use of them in poor groups will help improve impact.
The Authors of this review evaluated the efficacy, tolerability and safety of NTZ in patients with RRMS. Among the pertinent literature, 3 studies met the inclusion criteria of methodological quality, comprising a total of 2223 participants. The results show that NTZ treatment reduces the number of patients who experienced relapses and the number of patients who progressed at 2 years. Also Magnetic Resonance scans show evidence of a beneficial effect of NTZ on disease activity. Although information on adverse events (AEs) was limited, as most participants were followed up for 2 years only, infusion reactions, anxiety, sinus congestion, lower limb swelling, rigors, vaginal inflammation and menstrual disorders were found to be more frequent after NTZ treatment. However, the number of patients experiencing at least one AE (including severe or serious AEs) did not differ between NTZ and control groups. On the contrary, significant safety concerns have been raised regarding Progressive Multifocal Leukoencephalopathy (PML), a rare and often fatal viral disease characterized by damage to the white matter of the brain. In the studies included in this review, PML was reported in 2 patients treated with NTZ for more than 2 years. However, our protocol was insufficient to evaluate PML risk as well as other potential rare and long-term AEs (e.g. cancers and other infections) which are important issues in considering the risk/benefit ratio of NTZ. An independent systematic review of the safety profile of NTZ is warranted. NTZ should be used only by skilled neurologists in MS centres under surveillance programs. All the data in this review came from studies supported by the Pharmaceutical Industry. In agreement with the Cochrane Collaboration policy, this may be considered a potential source of bias.
In May 2016, we found three studies involving 1853 people. The main comparison was between the fixed-dose of dexketoprofen 25 mg plus tramadol 75 mg and placebo (a dummy treatment). The studies tested single doses after wisdom tooth extraction, hip replacement operations, and gynaecological (female reproductive system) operations. Studies included adults over a range of ages, and 7 out of 10 participants were women. The main outcome was the number of participants having at least half of the maximum possible pain relief over the first six hours after taking the tablets. All three studies reported the main outcome for dexketoprofen 25 mg plus tramadol 75 mg. There were 748 participants in the comparison with placebo. About 7 in 10 people achieved this outcome with dexketoprofen 25 mg plus tramadol 75 mg, compared with 3 in 10 with placebo. The combination was significantly better than placebo, and better than either dexketoprofen or tramadol alone. The pain relief lasted a long time, probably eight hours or more, but the exact duration could not be determined. Fewer people needed to take additional painkillers with the combination treatment than with placebo. About 1 in 10 people had side effects with dexketoprofen 25 mg plus tramadol 75 mg. These were mostly mild or moderate nausea (feeling sick), vomiting (being sick), and dizziness, which are typical with these medicines. Serious side effects were uncommon. Few people dropped out of the studies. We judged the quality of the evidence as moderate for the painkilling effect of dexketoprofen 25 mg plus tramadol 75 mg. For side effects we judged the quality of the evidence about a single dose as very low because there were so few participants and events, but we judged it as moderate when we included evidence from the three- and five-day studies. Moderate quality evidence means that more information might change our estimate of the effect. Very low quality evidence means that we are very uncertain about the results.
No new studies were included for this update. Seven studies with 802 participants were included in this review. The review of trials found that the benefit of heparin, LMWHs and oral anticoagulants for treatment of intermittent claudication has not been established while an increased risk of major bleeding events has been observed, especially with oral anticoagulants. There is no clear evidence to support the use of anticoagulants for intermittent claudication at this stage. More research is needed.
This updated review included 20 small trials (N = 1239). We included adults (> 18 years old) with acute whiplash or non-specific neck pain as well as chronic neck pain including degenerative changes, myofascial pain or headaches that stem from the neck. No index for severity of the disorders could be specified. The evidence was current to August 2012. The results of the trials could not be pooled because they examined different populations, types and doses of electrotherapy and comparison treatments, and measured slightly different outcomes. We cannot make any definitive statements about the efficacy of electrotherapy for neck pain because of the low or very low quality of the evidence for each outcome, which in most cases was based on the results of only one trial. For patients with acute neck pain, TENS possibly relieved pain better than electrical muscle stimulation, not as well as exercise and infrared light, and as well as manual therapy and ultrasound. There was no additional benefit when added to infrared light, hot packs and exercise, physiotherapy, or a combination of a neck collar, exercise and pain medication. For patients with acute whiplash, iontophoresis was no more effective than no treatment, interferential current, or a combination of traction, exercise and massage for relieving neck pain with headache. For patients with chronic neck pain, TENS possibly relieved pain better than placebo and electrical muscle stimulation, not as well as exercise and infrared light, and possibly as well as manual therapy and ultrasound. Magnetic necklaces were no more effective than placebo for relieving pain; and there was no additional benefit when electrical muscle stimulation was added to either mobilisation or manipulation. For patients with myofascial neck pain, TENS, FREMS (FREquency Modulated Neural Stimulation, a variation of TENS) and repetitive magnetic stimulation seemed to relieve pain better than placebo. About 70% of the trials were poorly conducted studies. The trials were very small, with a range of 16 to 336 participants. The data were sparse and imprecise, which suggests that results cannot be generalized to the broader population and contributes to the reduction in the quality of the evidence. Therefore, further research is very likely to change the results and our confidence in the results.
This Cochrane review found only four old and small trials of poor quality that have compared the two types of drugs. There were a total of 121 patients in the four trials. In each trial, the patients tried both types of drugs, one after the other, in different periods of the trial. In the largest trial, of 54 patients, where each drug was tested twice, 20 patients preferred ibuprofen on both occasions, and 7 paracetamol. In the trials, each drug was used for only 4-7 days and side effects from the drugs were poorly reported. It is therefore not clear whether NSAIDs are better than paracetamol.
The review identified 27 studies involving 1803 children. Twelve studies declared funding from outside sources. One of these was funded by Astellas Pharma, while another study was provided with special batches of placebo and medication free of charge, as well as materials for pad tests free of charge from another company. Cochrane Reviews assess the 'certainty' or reliability of the evidence using standardised methods that consider the way studies were designed, conducted and reported, differences between studies or populations, and the combined results of studies. Most of the studies identified for this review were small and many were poorly designed and not reported clearly. Most of the evidence was considered to be of very low certainty, meaning that little can be said with any certainty about the effectiveness of treatments. Transcutaneous electrical nerve stimulation (TENS) may be more effective than no treatment for ending or reducing daytime wetting. We are uncertain whether urotherapy (behavioural programmes in which children - and sometimes carers - are taught about how the bladder works, proper toileting postures and methods, scheduled toileting, and planning what and how much to drink) is more effective when supplemented with PFMT, voiding education with feedback, or watches with alarms set to remind children when to go to the toilet. We are uncertain whether feedback that shows children how their muscles are working or how their bladder is emptying improves the effectiveness of TENS with urotherapy compared to PFMT plus feedback and urotherapy. We are also uncertain whether PFMT and urotherapy plus feedback improves the effectiveness of PFMT and urotherapy alone. We are uncertain whether pelvic floor muscle training (PFMT) or TENS are more effective than anticholinergics (drugs that can reduce signals from the brain that cause the bladder to contract and empty). We are uncertain whether voiding education plus uroflowmetry (a test to measure the volume of urine) and feedback increases the number of continent children compared to anticholinergics. No serious adverse events were reported that were considered to be related to study treatments. Most non-serious adverse events and side effects were mild or moderate in severity and were in children receiving pharmaceutical interventions. These included common pharmaceutical side effects such as nausea, abdominal pain, dry mouth, drowsiness and headache. There is a lack of good-quality research evidence that can help children, their carers and doctors and nurses to make decisions about treatments. More well-designed research may provide much needed evidence about the effectiveness of promising interventions in children with daytime urinary incontinence, such as TENS, PFMT and timers on watches (or mobile phones) to remind children about toileting schedules. However, it is hoped that this review will draw attention to the need for research into effective treatments for daytime wetting in children.
We found 196 studies involving 135,559 women. We compared seven uterotonic agents against each other and against women receiving no uterotonic. Studies were conducted across 53 countries. In most studies women were giving birth normally and in a hospital. The analysis suggests that all drugs are effective for preventing blood loss that equals or exceeds 500 mL when compared with no routine uterotonic treatment. Compared with oxytocin (the standard recommended drug), the three best drugs for this outcome were a combination of ergometrine plus oxytocin, carbetocin, and a combination of misoprostol plus oxytocin. We found the other drugs misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin. All drugs except ergometrine and injectable prostaglandins are effective for preventing blood loss that equals or exceeds 1000 mL when compared with no treatment. Ergometrine plus oxytocin and misoprostol plus oxytocin make little or no difference in this outcome compared with oxytocin. It is uncertain whether carbetocin and ergometrine alone make any difference to this outcome. However, misoprostol is less effective in preventing blood loss that equals or exceeds 1000 mL compared with oxytocin. Misoprostol plus oxytocin reduces the use of additional uterotonics and probably also reduces the risk of blood transfusion when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No meaningful differences could be detected between all agents for maternal deaths or severe birth complication as these are rare in such studies. The two combinations of drugs were associated with important side effects. When compared with oxytocin, women receiving misoprostol plus oxytocin combination are more likely to suffer vomiting and fever. Women receiving ergometrine plus oxytocin are also more likely to suffer vomiting and may make little or no difference to the risk of hypertension, however the certainty of the evidence was low for this outcome. The analyses gave similar results irrespective of whether women were giving birth normally or by caesarean, in a hospital or in the community, were at high or low risk for bleeding excessively after birth, whether they received a high or a low dose of misoprostol and whether they received a bolus or an infusion of oxytocin or both. All agents were generally effective for preventing excessive bleeding when compared with no uterotonic drug treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional benefits compared with the current standard oxytocin. The two combination drugs, however, are associated with significant side effects that women might find disturbing compared with oxytocin. Carbetocin may have some additional benefits compared with oxytocin and appears to be without an increase in side effects.
We included 31 trials (1760 adult participants: 897 randomized to peripheral nerve blocks and 863 to no regional blockade) performed in various countries and published between 1980 and 2016. Trials were funded by a charitable organization (n = 3), by a governmental organization (n = 1) or by departmental resources (n = 5), or did not specify the source of funding. Compared with other modes of analgesia, peripheral nerve blocks used to treat hip fracture pain reduce pain on movement better within 30 minutes (equivalent to a difference of -3.4 on a scale from 0 to 10 between the two analgesic regimens). The risk of pneumonia is also reduced when peripheral nerve blocks are used to treat hip fracture pain. For every 7 people with a hip fracture, one less person will suffer from pneumonia. Studies noted no major complications related to peripheral nerve blocks and reported reduced time to first mobilization after hip fracture surgery (approximately 11 hours earlier). We did not identify enough trial participants to determine if regional blockade makes a difference in terms of acute confusion, myocardial ischaemia and death within six months after surgery. Peripheral nerve block given as a single injection led to reduced cost of analgesic drugs. We rated the quality of evidence as high for reduction of pain on movement within 30 minutes, and as moderate for pneumonia, time to first mobilization and costs of analgesic drugs. We would need more information before we could draw final conclusions on effects of peripheral nerve blocks on the risk of acute confusional state, myocardial ischaemia and mortality.
This review identified two small randomized controlled trials that included a total of 46 participants. One study compared 12 weeks of treatment with low dose naltrexone (4.5 mg/day) to a placebo (i.e. a fake drug such as a sugar pill) in 34 adult patients with active Crohn’s disease. The other study compared eight weeks of treatment with low dose naltrexone (0.1 mg/kg up to a maximum 4.5 mg/day) to a placebo in 12 children with active Crohn's disease. The results from both studies were imprecise with regard to the proportion of patients who achieved clinical remission. The results of the study in adult patients suggest that low dose naltrexone may provide a benefit in terms of clinical response (i.e. an improvement in disease symptoms) and endoscopic response (i.e. a reduction in inflammation of the gut as shown by examining the gut with a scope). We could not tell whether low dose naltrexone led to specific side effects including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue due to the low number of people who experienced these problems in the studies. The results of this review need to be interpreted with caution as they are based on small numbers of patients and the overall quality of the evidence was rated as low due to lack of precision of the results. Thus no firm conclusions can be made regarding the effectiveness and side effect profile of low dose naltrexone treatment for patients with active Crohn's disease. Further randomized controlled trials are required to assess the effectiveness and side effects of low dose naltrexone therapy in active Crohn's disease in both adults and children.
We reviewed the benefits and harms of treating patients who have the form of the disease that affects the lungs with alpha-1 antitrypsin extracted from blood donations. We found three randomised clinical trials (283 participants in the analyses) comparing treatment with alpha-1 antitrypsin with placebo (a pretend treatment) for two to three years. All participants were ex-smokers or had never smoked but had the genetic problem that carried a high risk of developing lung problems. The evidence is current to March 2016. Only one trial reported deaths (one of 93 participants died taking the medicine and three of 87 died taking placebo). There was no information on harms in the oldest trial. In another trial, serious adverse events occurred in 10 participants in the medicine group and 18 participants in the placebo group. In the most recent trial, serious adverse events occurred in 28 participants in each group. None of the trials reported on the number of lung infections or hospital admissions. There were more exacerbations (acute worsening in lung function) in the medicine group than in the placebo group, whereas quality of life was similar in the two groups. All trials measured lung function using forced expiratory volume in one second (how much air a person can breathe out during a forced breath) and carbon monoxide diffusion (a medical test that measures how much gas travels from the lungs to the blood). Lung function was slightly worse in participants taking the medicine but the differences were not significant. Lung function deteriorated significantly less when measured by a special type of X-ray called a computer tomography (CT) scan. Several secondary outcomes were unreported in the largest and most recent trial whose authors had numerous financial conflicts of interest. Due to a lack of information, we cannot be sure whether this treatment works or not. Therefore, it is our opinion that treatment with alpha-1 antitrypsin augmentation cannot be recommended.
We found two randomised controlled studies (RCTs), with a total of 361 participants that compared a single-dose chemotherapy placed in the bladder to no chemotherapy in people having their kidney and ureter removed for cancer of the inner lining of the kidney or ureter, or both. These findings are based on a literature search up to April 15, 2019. We found that a one-time dose of chemotherapy put into the bladder after surgery may reduce the risk of this type of tumor coming back in the bladder over time compared to no chemotherapy. We found no evidence whether this affects the time to death from this type of cancer. Serious unwanted effects appear to be rare and not increased with chemotherapy, but we are uncertain of this finding. Our confidence in the evidence for the effect on the risk of recurrence within the bladder is low. This means that the true effect may be very different from what this review shows. The certainty of evidence for the effects of one-time chemotherapy put into the bladder on serious unwanted effects was very low. This means that we are very uncertain about this result.
Results from 16 randomized controlled trials, predominantly of moderate to good quality, involving 994 selected participants, approximately two thirds with chronic obstructive pulmonary disease who had respiratory failure and were starting to breathe spontaneously, demonstrate that support with noninvasive ventilation can decrease death, weaning failure, pneumonia and length of stay in the intensive care unit and hospital. Noninvasive weaning also decreased the total duration of ventilation and the time spent on invasive ventilation, as well as the number of participants who received a tracheostomy. Although noninvasive weaning had no effect on the duration of mechanical ventilation related to weaning, it did not increase the reintubation rate. Insufficient data were available to assess its impact on quality of life. Noninvasive weaning significantly reduced mortality in chronic obstructive pulmonary disease studies versus mixed population studies.
We reviewed studies of psychotherapies, including a specific form of psychotherapy called cognitive behavioural therapy (CBT-BN). We compared psychotherapy to control groups who got no treatment (e.g. people on waiting lists) and the specific CBT-BN with other types of psychotherapy. We found that CBT was better than other therapies, and better than no treatment, at reducing binge eating. Other psychotherapies were also better than no treatment in reducing binge eating. Some studies found that self-help using the CBT manual can be helpful, but more research and larger trials are needed.
This review included 12 studies that comprised a total of 1837 participants. Eleven studies that included 1826 participants contributed to the quantitative syntheses. Participants were all adults, but ranged in demographics and trauma types. All studies recruited participants in the United States and there was a predominance of studies conducted on military veterans. PCT does not appear to be as effective as trauma focused treatments in reducing PTSD severity at post-treatment. However, PCT is associated with reduced treatment dropout rates compared to TF-CBT. Several of the TF-CBT trials included in this review were well designed and executed. However, we assessed the overall quality of evidence for our primary outcome (post-treatment PTSD severity) as low based on inconsistent outcomes and some imprecision in the results. We rated the quality of the evidence on differential treatment dropout as moderate.
We found 1952 potential titles. From these we found five studies which met our inclusion criteria, including a total of 1713 women with advanced ovarian cancer. We were able to pool data from four studies. These studies compared women who were given chemotherapy prior to surgery (NACT) with women who underwent surgery first (PDS) prior to chemotherapy. We found little or no difference between the two treatments with respect to the time to death or the time to progression of the disease. We found that giving NACT probably reduces the risk of some complications of surgery, but these data were less well reported in the included studies and so we have low certainty about these results. The studies only enrolled women with stage IIIc/IV ovarian cancer i.e. those who had advanced disease; a large proportion of women in this review had very bulky tumours. We are currently awaiting results of two ongoing studies and one unpublished study that will hopefully contribute more evidence to guide clinical practice in this area in the future. Overall, the evidence was of moderate certainty. There is probably little or no difference in how long women with advanced epithelial ovarian cancer will survive, if they have chemotherapy or surgery first, where both treatments are planned. NACT may reduce some of the risks of surgery, and probably halves the risk of needing bowel removed and/or the bowel diverted through the abdominal wall via a stoma (a bag attached to the abdominal wall to collect bowel contents). NACT/IDS is an alternative to PDS followed by chemotherapy in women with bulky stage IIIc/IV disease. Individual decisions about which treatment to have first will depend on the individual woman's wishes, how well she is at the time of diagnosis, the risks of surgery and the burden and distribution of disease.
We used a set of tests to ensure that the evidence the five studies identified reached the quality standard for our analysis.The analysis of three studies combined (meta-analysis), assessing over 9000 women, suggested that institutions with gynaecologic oncologists (specialists in the field of gynaecological cancer treatment) on site may prolong the lives of women with ovarian cancer compared to community or general hospitals. Similarly, another meta-analysis of three studies which assessed well over 50,000 women, found evidence to suggest that teaching centres or regional cancer centres (specialised centres) may prolong the lives of women with gynaecological cancer compared to community or general hospitals. The largest study in this meta-analysis assessed all gynaecological cancers in 48,981 women, so it had major influence on the final result; this means that our findings are likely to be relevant to other gynaecological cancers, besides ovarian cancer. Overall, the findings suggest that centralisation of care may prolong the lives of women with gynaecological cancer, and in particular ovarian cancer. However, the results should be interpreted with caution as all of the studies included in the review could be biased. For example, it is possible that the patients who were treated in specialised centres were less ill to begin with. Another weakness of the review is that only one of the studies included women with gynaecological cancers other than ovarian cancer. Ideally, further studies in this area are needed.  New studies should be designed to avoid the possibility of bias due to the treatment of women at specialist and non-specialist centres being systematically different. Additionally, studies should assess the impact of centralisation of care on the quality of life of patients. Most of the available evidence was about ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers and to less developed countries.
After searching the medical literature for relevant trials, we identified 36 clinical trials that recruited 6044 pregnant women with signs of HBV infection. All trials originated from China. All trials and trial results were at high risks of bias, which makes potential overestimation of benefits and underestimation of harms more likely. The studies assessed only hepatitis B surface antigen (HBsAg) (proteins on the surface of the HBV that cause immune system of the body to make antibodies when exposed to HBV), hepatitis B virus DNA (HBV-DNA) (self-dividing material of the HBV which carries its genetic information), and hepatitis B envelope antigen (HBeAg) (blood proteins that shows that the virus is still active in the liver) status in newborns. There was no information about the effects of HBIG on death from all causes (newborn or mother), antibodies to hepatitis B core antigen (proteins made by the immune system which bind to HBV and cause them to be destroyed), cost-effectiveness of HBIG, and side effects. Antenatal (before birth) HBIG might have an effect on preventing mother-to-child transmission of HBV as more treated babies than non-treated babies had no HBsAg or HBV-DNA; however, both results could have been affected by the way the trials were conducted and were at high risk of bias. The authors could draw no conclusions about the side effects of HBIG for pregnant women with HBV infection. Well-designed clinical trials with low risks of bias are needed to establish the benefits and harms of HBIG compared with no treatment in pregnant women with HBV. Due to the very low to low quality evidence in this review, we do not know if antenatal HBIG administration has an effect on the proportion of newborns with HBsAg and HBV-DNA compared with no treatment. We could draw no conclusions about death of newborns or mothers as we found no data.
The studies were of mixed quality. Overall, the results of this review show that giving children supplements with iron alone or in combination with other vitamins and minerals one, two or three times a week approximately halves their risk of having anaemia in comparison with receiving no iron supplements or a placebo. Giving children supplements on a intermittent basis was as effective as daily supplementation for improving haemoglobin and ferritin concentrations, although, children receiving iron supplements intermittently were at higher risk of having anaemia. We aimed to examine the effects of intermittent supplementation on illness, death, and school and physical performance, as well as on other side effects, but there was insufficient information to draw firm conclusions. In summary, intermittent iron supplementation is efficacious to improve haemoglobin concentrations and reduce the risk of having anaemia or iron deficiency in children younger than 12 years of age when compared with a placebo or no intervention, but it is less effective than daily supplementation to prevent or control anaemia. Intermittent supplementation may be a viable public health intervention in settings where daily supplementation has failed or has not been implemented. Information on mortality, morbidity, developmental outcomes and side effects, however, is still lacking.
The literature searches are up-to-date as of 19 February 2018. We found two small randomised controlled trials with a total of 141 preterm infant participants that compared routine monitoring versus no monitoring of stomach aspirates in preterm infants. We found one trial for the comparison of using two different criteria of aspirates to interrupt feeds while monitoring stomach aspirates in preterm infants. There is uncertainty as to whether routine monitoring of stomach aspirates reduces necrotising enterocolitis because trial results are imprecise. Preterm infants on routine monitoring of stomach aspirates may reach full feeds later, regain birth weight later, require longer duration of parenteral nutrition, and may be at increased risk of feed interruption episodes. There is uncertainty as to whether using two different criteria of gastric residual to interrupt feeds has effect on important outcomes in preterm infants. There is uncertainty as to whether routine monitoring of stomach aspirates has any benefits. Routine monitoring may increase the number of feed interruption episodes and the time taken to reach full feeds.
We searched for evidence on 28 June 2016 and found 15 randomised studies, involving 6008 women. Thirteen of these studies provided data we could use. The quality of results ranged from very low to high (GRADE). Most studies had design limitations, which in some were serious. Most studies compared women taught how to check for signs of premature labour with women who were also given a home uterine activity monitor. In some studies both groups used a monitor but one group had a ‘sham’ monitor that did not actually send the data to the women’s healthcare providers.Using a monitor at home made very little difference to many of the outcomes for mother or baby, although not all studies measured all outcomes. Women using monitors were no less likely to experience preterm birth at less than 37 or 32 weeks of pregnancy (GRADE very low). Women using monitors were less likely to experience preterm birth at less than 34 weeks, but when we analysed only high-quality studies, no clear difference remained (GRADE high). Babies born to women using the monitor were less likely to be admitted to neonatal intensive care (GRADE moderate) but there were no fewer deaths (GRADE low). Women using the monitor were more likely to make an unscheduled antenatal visit (GRADE moderate), but the number of antenatal hospital admissions did not differ (GRADE low). Women using monitors appeared to be more likely to receive tocolysis (treatment to stop labour) (GRADE low), but when we looked only at high-quality studies there was no clear difference. We found no data to assess women's views, although one large trial reported low compliance with monitor use. In some studies, women with monitors had more contact with midwives or maternity nurses, but it is unclear what effect this had. Home uterine monitoring may result in fewer admissions to a neonatal intensive care unit, but more unscheduled antenatal visits and treatment for preterm labour. The level of evidence is generally low to moderate.
We found 15 studies that compared macrolides with placebo (a substance or treatment with no benefit) or no intervention. Eleven studies involved 690 adults (aged 18 years and older) and four studies involved 190 children. Among adults, six used azithromycin, four roxithromycin, and one erythromycin. The four studies with children used azithromycin, clarithromycin, erythromycin, or roxithromycin. This review is current to January 2018. The studies on azithromycin reported improved quality of life in adults. We do not have sufficient evidence from other macrolides to make a robust judgement on their use, and we similarly have insufficient evidence from children to draw clear conclusions. Although we found only a few trials, they do show a possible increase in antibiotic resistance. Antibiotic resistance is seen when an antibiotic becomes less effective at killing the bacteria causing the chest infection. We know that macrolides are associated with higher risk of cardiovascular death and other serious adverse events when they are used to treat other conditions. The data in our review suggest it is possible that people with bronchiectasis are at risk for these adverse effects when taking macrolides. Generally the limited number of studies evaluating macrolides and the variation among them indicate that we cannot be sure of the overall effect of their use in bronchiectasis. Further high-quality studies are needed to examine the role of long-term macrolide antibiotics in the treatment of adults and children with bronchiectasis.
This review sought evidence to compare other types of drugs with anticholinergics. Only a few, small-scale randomised trials were found, many testing drugs that are no longer used clinically. The review found inadequate evidence to assess whether or not available alternative drugs are better or worse than anticholinergics in the management of people with symptoms of overactive bladder syndrome.
This review included ten research studies that randomly assigned a total of 928 women to follicular aspiration alone or follicular flushing after aspiration. To see if there was a difference between the two techniques, we wanted to look at the main results of live birth rate (number of babies born per 1000 women) and miscarriage rate (number of miscarriages per 1000 women). We carried out a comprehensive search to identify all relevant research in this field available in July 2017. Three studies reported on the main result of live birth rate and noted that follicular flushing probably has little or no effect on live birth rate compared with aspiration alone (moderate-quality evidence). This suggests that if a live birth rate of approximately 41% is seen with aspiration alone, the equivalent live birth rate with follicular flushing is likely to lie between 29% and 52%. None of the included studies reported on the miscarriage rate. Studies also found that follicular flushing probably makes little or no difference in the number of eggs retrieved, the number of embryos, or the clinical pregnancy rate compared with aspiration alone. Although the quality of evidence was very low, it appears that follicular flushing takes much longer to perform than aspiration alone. Evidence was insufficient to permit any firm conclusions with respect to adverse events or safety. More research is needed to find out whether any specific patient groups would benefit from follicular flushing. The quality of evidence for the main outcome of live birth rate was moderate. The quality of evidence for the other outcomes ranged from very low to moderate. The main limitations of included studies were lack of blinding (the process whereby women participating in the trial as well research staff are not aware of the intervention used), inconsistency (differences between different studies), and imprecision (insufficient data).
The evidence in this review, which was carried out together with Cochrane Oral Health, is up-to-date as of 13th September 2016. We included six studies that evaluated 916 participants and 988 teeth, who were undergoing retrograde filling using different types of filling material: mineral trioxide aggregate (MTA), intermediate restorative material (IRM), super ethoxybenzoid acid (Super-EBA), dentine-bonded resin composite, glass ionomer cement, and amalgam. Five studies were conducted in Europe and one in Asia. Studies measured the success rate with clinical or radiological methods. None of the studies reported possible side effects. The limited evidence is insufficient to draw any conclusion as to the benefits of any one material over another, so we are not able to recommend which material is best to use in retrograde filling at present. The evidence presented is of very low quality due to the small amount of available studies, all at high risk of bias, results were imprecise and may not be applicable to other settings/countries.
The evidence is current to January 2013. We included 16 studies covering 697 participants with MCI. The studies have been published over a 14-year period (1999 to 2013). Study sizes were small and ranged from 19 to 94 participants. Five papers have a mean age of less than 70 years. The age range in the youngest sample was 55 to 73 years and in the oldest sample was 71 to 86 years. Participants were mainly recruited from university departments, clinics or research centres. The percentage of participants with positive ¹⁸F-FDG PET scans at baseline ranged in the included studies from 10.5% to 74% and the percentage of those participants who converted to Alzheimer’s disease dementia over a period of time ranged from 22% to 50%. Included studies reported a range of different cut-off values used for identifying their participants with positive ¹⁸F-FDG PET scans. Our findings are based on studies with poor reporting. The majority of included studies had an unclear risk of bias, mainly because they did not describe in sufficient details how participants were selected and how the clinical diagnosis of Alzheimer’s disease dementia was justified. According to the assessment of the ¹⁸F-FDG PET test domain, more than 50% of studies were of poor methodological quality. The main limitations of the review are poor reporting in the included studies, a lack of a widely-accepted cut-off value of the ¹⁸F-FDG PET scan in people with MCI, and the marked variation in test accuracy between the included studies. In this review, we have found that the ¹⁸F-FDG PET scan, as a single test, lacks the accuracy to identify those people with MCI who would develop Alzheimer’s disease dementia or other forms of dementia over a period of time. Assuming a typical conversion rate of MCI to Alzheimer’s disease dementia of 38%, the findings indicate that for every 1000 ¹⁸F-FDG PET scans, 174 cases with a negative scan will progress to Alzheimer's disease dementia and 285 with a positive scan will not. Therefore, a positive ¹⁸F-FDG PET scan in people with MCI is of no clinical value in early prediction of developing Alzheimer's disease dementia.
Our confidence in the results of the individual trials was limited by several potential biases in how they were conducted. We were not able to analyse the results of the two trials together because the experiences of people with spinal cord injury or burning mouth are too different from each other. On their own, the trials were too small for us to undertake any statistical analysis. However, neither trial found any clear benefit of treatment. We conclude that there is currently no evidence that will help practitioners and patients to decide whether to use these treatments. We discuss what studies are needed.
One study with a total of 28 participant was included in the review. This study compared two methods of splenectomy - laparoscopic (keyhole) versus an open surgical approach. Study participants were recruited over a period of 3.5 years, but participants were only followed up to the end of their hospital stay (usually less than one week). The study evaluated the two types of surgical methods. Only one of our three primary outcomes were reported, the number of people experiencing major adverse events (bleeding during and after the operation and complete or partial collapse of a lung). However, the amount of information available is not sufficient to draw any reliable conclusions (very-low quality evidence). Hence, we were unable to provide recommendations regarding the use of splenectomy in people with thalassaemia. Appropriate clinical judgement, in view of the various risks and benefits described by other lower quality sources of evidence (e.g. observational studies), may be necessary when considering splenectomy in people with thalassaemia. While we are satisfied that the participants had equal chances of undergoing either type of surgery, there is not enough information on other aspects of the study to make any overall judgement on its quality.
We searched medical databases for clinical trials of the use of laxatives for constipation in people receiving palliative care. Two review authors assessed study quality and extracted data. We identified five studies involving 370 people. The laxatives evaluated were lactulose, senna, co-danthramer combined with poloxamer, docusate and magnesium hydroxide combined with liquid paraffin. Misrakasneham was also evaluated; this is a traditional Indian medicine and is used as a laxative, containing castor oil, ghee, milk and 21 types of herbs. There was no evidence on which laxative provided the best treatment. However, the review was limited as the evidence was from only five small trials and patient preference and cost were under evaluated. Further rigorous, independent trials are needed to evaluate the effectiveness of laxatives.
Study characteristics: we included six randomised controlled trials conducted in the UK, France, Spain, Israel and the US, including 781 women. They compared monitoring with TVUS only versus TVUS plus serum estradiol concentration in women undergoing ovarian hyperstimulation for IVF and ICSI treatment. The evidence was current to May 2014. Key results: none of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate between monitoring with TVUS only and monitoring with TVUS plus estradiol measurement (odds ratio (OR) 1.10; 95% CI 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). Our findings suggest that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%. There was no evidence of a difference in OHSS between the two arms (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUS only was between 2% and 8%. Quality of the evidence: the evidence was of low quality. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in the treatment protocols. Quality assessment was hampered by a lack of methodological descriptions in several studies. Two studies reported funding by pharmaceutical companies, whereas the remaining four studies did not report their sources of funding.
This summary of an updated Cochrane review presents what we know from research about the benefits and harms of electrotherapy modalities in people with frozen shoulder. After searching for all relevant studies published up to May 2014, we included 19 trials (1249 participants). Of the included participants, 61% were women, the average age was 55 years, and the average duration of the condition was 5.5 months. The average duration of delivery of electrotherapy interventions was four weeks. Pain (higher scores mean worse pain) People who received LLLT and exercise had less pain than people who had placebo plus exercise - pain was 19 points less (ranging from 15 to 23 points less) at the fourth week of treatment (19% absolute improvement, ranging from 15% to 23% improvement). - People who had LLLT and exercise rated their pain score as 32 points on a scale of 0 to 100 points. - People who had placebo and exercise rated their pain score as 51 points on a scale of 0 to 100 points. Function impairment (higher scores mean worse function impairment) People who received LLLT and exercise had less function impairment than people who had placebo and exercise - function impairment was 12 points less (ranging from 6 to 18 points less) at the fourth week of treatment (12% absolute improvement, ranging from 6% to 18% improvement). - People who had LLLT and exercise rated their function impairment as 36 points on a scale of 0 to 100 points. - People who had placebo and exercise rated their function impairment as 48 points on a scale of 0 to 100 points. Active shoulder abduction (higher degrees of movement mean greater shoulder abduction) People who received LLLT and exercise had greater active shoulder abduction than people who had placebo and exercise - active shoulder abduction was 9 degrees more (ranging from 2 to 16 degrees more) at the fourth week of treatment (5% absolute improvement, ranging from 1% to 9% improvement). - People who had LLLT and exercise had active shoulder abduction of 79 degrees. - People who had placebo and exercise had active shoulder abduction of 70 degrees. Side effects No person in either group reported any side effects. Participant-reported pain relief of 30% or greater, global assessment of treatment success, and quality of life These were not measured in this trial. There was low quality evidence that LLLT for six days may improve global assessment of treatment success more than placebo, when measured at six days. Further research is likely to change the estimate. We are very uncertain about whether PEMF for two weeks improves pain or function any more than placebo because of the very low quality evidence from one trial. There was moderate quality evidence that LLLT plus exercise for eight weeks may improve pain, up to four weeks, and function, up to four months, more than placebo plus exercise. Further research may change the estimate. We are very uncertain about whether therapeutic ultrasound, PEMF, Iodex phonophoresis, continuous short wave diathermy, a combination of Iodex iontophoresis with continuous short wave diathermy, or a combination of therapeutic ultrasound with transcutaneous electrical nerve stimulation (TENS) are effective adjuncts to exercise.
The review authors found two relevant studies. Both of these studies were from the USA and both assessed policies that were introduced in the late 1990s. The first study assessed a policy that aimed to get doctors to prescribe antihistamines that were cheaper but considered to be just as good as other antihistamines. In one part of the study, letters were sent to doctors and to their patients telling them about the new policy, and giving them information about the antihistamine. In another part of the study, letters were only sent to doctors. The second study assessed a policy that aimed to get doctors to prescribe fewer benzodiazepines to certain types of patients. This policy required doctors in the State of New York to fill in three copies of the same form each time they prescribed benzodiazepines. Pharmacies then sent one of these copies to a state surveillance unit that monitored what doctors were prescribing. The study compared these doctors to doctors in the State of New Jersey, who were not monitored in the same way. Because the evidence from both of these studies was of very low certainty, we do not know what effects these policies had on people’s medicine use. We also do not know whether these policies had any effect on people’s health or their use of healthcare services or on costs because the studies did not measure this. How up to date is this review? The review authors searched for studies that had been published up to March 2018.
We searched for studies up to May 2017, and we included four studies involving a total of 495 people with interstitial lung disease due to connective tissue disease. Some people were given cyclophosphamide, and others were given other drugs or a placebo. We compared these different groups to look for differences. We found some low-quality evidence showing small benefit of using cyclophosphamide compared with placebo in terms of lung function and symptoms of breathlessness. No clear evidence shows that people who took cyclophosphamide had better lung function than people who took a different drug (mycophenolate mofetil). Some people experienced low blood counts, blood in their urine, and nausea. We rated the quality of the evidence using one of the following grades: very low, low, moderate, or high. A rating of very low-quality evidence means that we are uncertain about the results. A rating of high-quality evidence means that we are very certain about the results. For this Cochrane review, we found evidence of low quality. We included randomised controlled trials that were blinded, which means that participants and those people who assessed study results did not know whether participants had received cyclophosphamide or a placebo. However, the trials mostly included people with systemic sclerosis, so these results may not apply to all people with interstitial lung disease with connective tissue disease.
This review focuses on travel plans for organisations, such as workplaces or schools. The main reasons for using travel plans are to reduce congestion and to be environmentally friendly, but travel plans are also commonly claimed to improve health. We included 17 studies in this review. One study found that promoting walking in a workplace improved some aspects of health, including mental health, but no other studies directly measured health effects. All 17 studies looked at changes in travel. Although some found that travel plans increased walking, others did not. Overall, there is not enough evidence to know whether travel plans are effective at changing the way people travel, or whether they improve health. Currently, organisational travel plans should be put in place as part of well-designed research studies.
We found only four trials from this search of the literature. All four trials in this review included participants with peripheral neuropathy and HCV-related cryoglobulinemia. There were no studies of HCV-related non-cryoglobulinemic peripheral neuropathy. Only one trial, in which there were results for 37 participants, reported effects on neuropathy. This study compared 48 weeks of rituximab and antiviral therapy versus antiviral therapy alone. Three trials, two of rituximab and one of interferon alfa (83 participants in total), reported adverse events. One trial of HCV-related cryoglobulinemia treated with rituximab and antiviral therapy versus antiviral therapy alone did not demonstrate any significant difference in the number of participants with improvement in neuropathy at 36 months post treatment. Two studies of rituximab (61 participants) and one of interferon alfa (22 participants) provided information on adverse events. Severe adverse events were no more common with interferon alfa or rituximab compared to the control group. All four trials had problems with their design or implementation that could have affected the results. High-quality studies of HCV-related peripheral neuropathy treatment are lacking. There is not enough evidence to make evidence-based decisions about treatment based on the results of this review. The evidence is current to August 2014.
We found six trials comparing different surgeries for PCG. These trials included 102 eyes of 61 children. Two trials were conducted in the USA and one trial in each of these four countries: Egypt, Israel, Lebanon and Saudi Arabia. All trials enrolled infants younger than one year when diagnosed with PCG, and followed them from six months to five years after surgery. No two trials compared the same pair of surgical interventions. One trial compared trabeculotomy versus goniotomy; the second trial compared combined trabeculectomy-trabeculotomy with mitomycin C (CTTM) versus trabeculectomy-trabeculotomy with mitomycin C with deep sclerectomy (CTTM-DS); the third trial compared combined trabeculotomy-trabeculectomy versus trabeculotomy; the fourth trial compared one goniotomy versus two goniotomies; the fifth trial compared trabeculotomy versus viscocanalostomy; and the sixth trial compared goniotomy using a blade versus a laser. The evidence is current to 23 June 2014. In our review, no two trials compared the same pair of operations. Further, there were small numbers of children included in each trial (average of 10 children per trial), thus limiting our ability to draw conclusions about the effectiveness of one surgery over another. Four trials reported adverse events, but no trial reported an important difference between pairs of operations. None of the trials reported quality of life or economic data. The overall quality of the evidence on our review topic was poor. All trials had some limitations in study design, reporting, or both. None of the trials enrolled enough participants to detect an evident difference between surgeries.
We found six small studies (involving 429 adults) of different fixation methods and bone fillers in September 2014. All six trials were small and at substantial risk of bias. We judged the quality of most of the available evidence to be very low, meaning that we are very uncertain about these results Three studies evaluated different methods of fixation. One study found that hybrid fixation is more likely to result in better quality of life and lower-limb function, fewer complications requiring repeat surgery, and more people returning to pre-injury activity levels than standard ORIF. However, the possibility of a better result from ORIF could not be ruled out. Another study compared a minimally invasive, single-plate technique with a traditional open technique using two plates. This study found very little difference between the two groups in knee function, complications or reoperations. The third study compared arthroscopic surgery (which uses a tiny camera to visualise the joint) and internal fixation versus ORIF. It reported better functional outcome and knee mobility in the arthroscopy group. There were no reoperations. Three studies compared different bone substitutes versus bone grafts for managing bone defects, but reported on only a few outcomes. One study found similar results in the two groups in the numbers of participants with good walking, stair climbing, squatting and jumping ability at one year. All three studies found similar numbers of specific complications in the two groups. One study found that all participants in the bone graft group had prolonged pain from the harvest site of the bone graft. Two studies reported similar range of motion results in the two groups, whereas the third study found better results in the bone substitute group at one year. Currently, there is insufficient evidence to ascertain the best surgical methods of fixation and bone defect treatment for tibial plateau fractures in adults. Well-conducted trials are still needed to inform clinical decision-making.
We identified four studies (including 206 participants) that investigated the effectiveness of technology-based interventions to rehabilitate children and adolescents with traumatic brain injury. All four studies were conducted in North America, with three originating from the same research team. One study with 120 participants used an online Counselor-Assisted Problem Solving (CAPS) intervention to rehabilitate executive functioning in adolescents aged 12 to 17 years. One study with 35 participants used a Teen Online Problem-Solving intervention to target the executive functioning of adolescents aged 11 to 18 years. One study with 40 participants used an online Family Problem Solving intervention to target outcomes such as behaviour and aspects of executive functioning in children aged 5 to 16 years. One study with 12 participants used a computer program to target cognitive-communication skills including memory and aspects of executive functions in adolescents and young adults aged 12 to 21 years. All funding sources were in the USA or Canada. One study was funded by the Colorado Department of Human Services and two National Institutes of Health (NIH) awards. A second study was also funded by a NIH grant. One study was funded by a hospital charity in addition to the Easter Seal Research Institute and Apple Canada. The final study was supported by the Ohio Department of Safety. This review found evidence that interventions employing technological aids did improve executive functions in adolescents with traumatic brain injury (i.e. a brain injury resulting from a road traffic accident, fall, or blow to the head). However, this result was relatively modest and is unlikely to have a clinically important effect on the child. One study employed technology to improve memory in adolescents with TBI and showed an improvement for the intervention group. It was not possible to determine how effective this approach was as the study failed to include adequate statistical information. Two studies examined the secondary outcomes of anxiety and depression but did not show any effect between the intervention and control groups at 6 months follow-up. Only one study recorded adverse events, and reported that none occurred. Two studies reported on the amount of use the intervention received. One study reported improvements in social functioning/social competence for the intervention group. No data were reported which related to the review's other secondary outcomes. We found the quality of evidence for all outcomes to be low, which means future research is likely to change the estimate of effect. All four studies were small, and it was not always possible to conceal group allocation to participants. Three studies failed to conceal group allocation to those who measured the outcomes.
We searched medical databases for clinical studies comparing different strategies regarding the frequency of endotracheal tube suction in newborn babies on ventilators. We found only one study recruiting 97 newborns with bodyweights under 2.5 kg (these are called low birthweight infants). Suctioning was performed every six or 12 hours during the first three days of life. There were no important differences on the time the babies were on the ventilator, occurrence of pneumothorax (collapsed lung), need for ventilation or oxygen at more than 30 days, bleeding in the brain, and death in the first month of life. In addition, the study reported no side effects. We only identified one study, which was conducted in 1987 and 1988 and had several shortcomings. We cannot advise health professionals and parents about the optimal frequency of suctioning when newborns are ventilated.
The researchers searched the medical literature up to 23 August 2018. Four published studies, including a total of 188 people, examined antidepressant therapy in people with IBD. The age of participants ranged from 27 to 37.8 years. In three studies participants had IBD in remission and in one study participants had either active IBD or IBD in remission. Participants in one study had co-existing anxiety or depression. One study used duloxetine (60 mg daily), one study used fluoxetine (20 mg daily), one study used tianeptine (36 mg daily), and one study used various antidepressants. Three studies had a placebo (e.g. sugar pill) control group and one study had a no treatment control group. The analysis showed that the symptoms of anxiety and depression were improved in those who took antidepressants compared to placebo. Participants who received antidepressants experienced more side effects than those who received placebo. Side effects reported by those taking antidepressants included: nausea, headache, dizziness, drowsiness, sexual problems, insomnia, fatigue, low mood/anxiety, dry mouth, poor sleep, restless legs and hot flushes. Some aspects of quality of life were improved as was IBD activity in the antidepressant group. The overall quality of the studies included in this review was poor because the studies included small numbers of participants, and involved IBD populations which differed from each other on key characteristics. In addition, different types of antidepressants were assessed so the evidence for any one antidepressant was uncertain. Therefore, future studies are needed to confirm these observations. The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the benefits and harms of antidepressants in IBD can be drawn. More studies are needed to allow for firm conclusions regarding the benefits and harms of the use of antidepressants in people with IBD.
We identified four trials with a total of 1365 participants in searches conducted up to June 2013: three trials compared the intravenous GP IIb-IIIa inhibitor Abciximab with intravenous placebo and one trial compared the intravenous GP IIb-IIIa inhibitor Tirofiban with intravenous aspirin. The results showed that GP IIb-IIIa inhibitors cause bleeding in the brain, and that this complication offset any benefits. Therefore, GP IIb-IIIa inhibitors should be avoided in people with acute ischaemic stroke. Overall, the studies were considered at low risk of bias.
we included nine studies involving 1282 critically ill patients receiving mechanical ventilation. Studies compared daily sedation interruption to strategies that did not include an interruption. Studies were conducted worldwide and involved both medical and surgical critically ill patients. we did not find strong evidence that daily sedation interruption reduced the duration of mechanical ventilation, length of stay in the intensive care unit (ICU) or hospital, death, or the amount of drug used. The effect on adverse events such as accidental removal of the breathing tube or invasive devices, or the rate of delirium was uncertain. However, tracheostomy was performed less often in those who were managed with daily sedation interruption. Sedation practices are known to vary worldwide, and as such an analysis of studies conducted in North America showed a reduction in time on the breathing machine for those who were managed with daily sedation interruption compared to those who were not. we advise caution should be applied when interpreting and applying our study findings. The results are based upon a small number of studies that were heterogeneous or not uniform in terms of methods, patients studied, and clinical management and our overall results only marginally crossed the no-effect line.
This review was updated in 2017. We included two randomized controlled trials (RCT; clinical studies where people are randomly put into one of two or more treatment groups), one involving 14 critically ill children with ARDS and one involving 67 critically ill adults with ARDS. The trials did not measure severity of illness, resolution of organ dysfunction, length of stay in intensive care unit or hospital, and quality of life. The study authors did not report side effects such as bleeding, organ dysfunction, airway reactivity or side effects unrelated to the intervention. None of the included trials reported receiving money from drug companies. Only the RCT involving children provided data on deaths, with no clear difference with and without prostacyclin. The RCT in adults reported a trend towards improved blood oxygen levels, for participants who were treated with alprostadil (prostaglandin E1). Therefore, we could not identify a clear advantage of the use of aerosolized prostacyclin in critically ill children or adults with low blood oxygen levels. The quality of the evidence was very low because of the limited number of participants and poor trial design. The RCT involving children used a cross-over design where one group received aerosolized prostacyclin first and the other group received saline (salt solution). They then changed over to the alternate treatment. There was insufficient information on the effect on death in both trials. We conclude that there is a need for a large-scale clinical trial with low risk of misleading information to investigate the advantages and harms of prostacyclin for critically ill people.
We searched for evidence on July 10, 2017. In this update, we have included 11 randomized controlled studies, involving a total of 3403 women undergoing cesarean section. Eight studies used povidone-iodine for vaginal cleansing, two chlorhexidine, and one benzalkonium chloride. The quality of the evidence using GRADE was moderate for the reported outcomes. We found that cleansing the vagina with an antiseptic solution compared to not cleansing or using saline or water immediately before the cesarean delivery more than halved the risk of post-cesarean infection of the uterus from a rate of 8.7% down to a rate of 3.8% (10 studies, 3283 women). While we should be cautious about results found for women in certain groups, we did also find that the benefit was also seen if the woman's waters had already broken (from 17.9% to 4.3% with vaginal cleansing; three studies, 272 women) and if women were already in labor at the time of the cesarean delivery (from a rate of 11.1% down to 4.7% with vaginal cleansing; four studies, 960 women women). The benefits were similar using both povidone-iodine and chlorhexidine. The risk of experiencing a fever (eight studies, 3109 women) or wound infection (eight studies, 2839 women) after the cesarean delivery may be slightly lowered by antiseptic preparation, but the results were not entirely clear. Only the composite outcome of wound complication or endometritis was reduced overall for women receiving preoperative vaginal cleansing (two studies, 499 women). None of the reports mentioned that any women had adverse events such as an allergic reaction to the cleansing solution or irritation. Cleansing the vagina immediately before a cesarean delivery with either an iodine-based or chlorhexidine-based solution probably reduces the risk of infection of the uterus after a cesarean section. This benefit may be greater for women who have their cesarean delivery after their membranes have already ruptured or they are already in labor. This is a generally simple, well-tolerated way to lower the chances of developing an infection after having a baby by cesarean.
The authors reviewed the results of all randomized trials that compared an aldose reductase inhibitor with a control and lasted at least six months. Many of the 32 randomized controlled trials identified had significant methodological flaws. The trials used a variety of measures to look for a benefit of treatment with aldose reductase inhibitors. The authors elected to focus primarily on changes in muscle strength and sensation. These were chosen because they are thought be the best indicator of the severity of polyneuropathy, and they have been used in a previous landmark study of the effects of intensive blood sugar control on diabetic neuropathy, as well as in studies of treatments in other types of polyneuropathy. Muscle strength or sensation were assessed in 29 trials, but sufficient data for analysis was only available in 13 studies, involving 879 treated participants and 906 controls. There was no overall significant difference between the treated and control groups. For one drug, tolrestat, there was possibly some benefit, but concerns about liver toxicity have lead to withdrawal of tolrestat from use in humans. A few trials did report that symptoms of neuropathy improved for the treated group, but this was contradicted by most other trials. No benefit was detected on electromyography (EMG) parameters (27 studies) or foot ulceration (one study). Quality of life was not assessed in any of the studies. Adverse effects were infrequent and were mostly minor, except for severe allergic reactions with sorbinil, impaired kidney function with zenarestat, and alteration of liver function with tolrestat. The authors concluded that there was no significant benefit of treatment with aldose reductase inhibitors for diabetic polyneuropathy.
In January 2015, we performed searches to look for clinical trials where nortriptyline was used to treat neuropathic pain in adults. We found six studies, with 310 participants with various neuropathic pain conditions. Studies were randomised and double-blind, but often with small numbers of participants. It was not possible to combine information from the different studies, but individually most studies indicated equivalent benefit from nortriptyline (usually at a dose between 50 mg and 100 mg daily) when compared with amitriptyline or chlorimipramine (other antidepressants), gabapentin (an antiepileptic), morphine (an opioid), or placebo (very low quality evidence). More people experienced adverse events with nortriptyline than with placebo, but numbers were similar for nortriptyline and other active medicines (very low quality evidence). There was too little information of adequate quality to be sure that nortriptyline works as a pain medicine in the type of neuropathic pain studies in this review. Other medicines have been shown to be effective.
In total, we have included 41 studies in 27,951 adults and eight studies in 8453 children. Almost all studies used a combination inhaler to deliver salmeterol with ICS and compared this with the same dose of ICS for an average of six months. We did not find a difference in the risk of death or serious adverse events in either adults or children. Eleven of a total of 14,233 adults taking regular salmeterol and ICS died, as did 13 of 13,718 adults taking regular ICS at the same dose. For every 1000 adults treated for 25 weeks, researchers reported one death on ICS alone and a corresponding risk on salmeterol and ICS of one death (95% confidence Interval (CI) 0 to 2 deaths). No deaths in any studies were attributed to asthma, and researchers reported no deaths at all among children. A non-fatal serious adverse event of any cause occurred in 332 adults on regular salmeterol with ICS compared to 282 adults on regular ICS alone. For every 1000 adults treated for 25 weeks, 21 serious adverse events occurred on ICS alone, and the corresponding risk on salmeterol and ICS was 23 adults (95% CI 20 to 27). A total of 65 of 4229 children on regular salmeterol with ICS suffered a serious adverse event of any cause compared to 62 of 4224 children on regular ICS alone. For every 1000 children treated for 23 weeks, 15 serious adverse events occurred on ICS alone, and the corresponding risk on salmeterol and ICS was also 15 children (95% CI 11 to 22). Reviewers assessed the overall risk of bias for all-cause events as low. The two new large studies performed independent assessment to identify the cause of asthma-related serious adverse events. This makes current data on asthma events more reliable than previously reported. Trials reported no asthma deaths among 27,951 adults or 8453 children randomised to regular salmeterol and ICS or ICS alone over an average of six months. The risk of dying from asthma while receiving either treatment was therefore very low, but we remain uncertain about whether the risk of dying from asthma is altered by adding salmeterol to ICS. We can now say that the worst-case estimate (safety margin) from this review is that at least 152 adults and 139 children must be treated with combination salmeterol and ICS for six months for one additional person to be admitted to the hospital (compared to ICS alone). These possible risks must be weighed against the benefits experienced by people who take combination treatment. People monitored in the new trials took over 90% of their prescribed treatment. This is much more than the average amount of medication that people take outside a trial. Therefore the effects shown in trials may be different from the effects experienced by people at home who are not taking their inhalers as prescribed. Because very few people die of asthma, trials would have to be very large to detect differences in the death rate. Therefore it is probably not feasible to find out if adding salmeterol to ICS causes more deaths among participants in randomised controlled trials - as these trials would be very large, difficult to run, and expensive. It might be better to use case-control studies or to review asthma deaths (e.g. from medical records).
In May 2016, we searched for clinical trials in which antipsychotics were used to treat symptoms of fibromyalgia in adults. We found a total of four studies with 298 participants. We found three studies with 208 participants, which were eight and 12 weeks long and compared quetiapine, an antipsychotic, against a fake medication (placebo). One hundred and sixty-six participants were diagnosed with major depression. We also found one study comprising 90 patients that compared quetiapine to an antidepressant named amitriptyline, which is frequently used in the treatment of fibromyalgia. Five people in this study were diagnosed with major depression. Quetiapine was not better than a fake medication in achieving a pain reduction of 50% or more (very low quality evidence). Quetiapine was better than the fake medication in achieving a pain reduction of 30% or more, reducing sleep problems, and improving depressed mood and anxiety (very low quality evidence). Quetiapine was better than the fake medication in improving health-related quality of life. Fewer participants dropped out of the trial due to lack of efficacy with quetiapine than with fake medication (very low quality evidence). There was no difference in tolerability and safety between quetiapine and a fake medication (very low quality evidence). For some people, quetiapine led to substantial weight gain and somnolence (sleepiness). Quetiapine and amitriptyline (an antidepressant which is frequently used to improve sleep and reduce pain in people with fibromyalgia) did not differ in the reduction of average scores for pain, fatigue, sleep problems, depression, anxiety and for limitations of health-related quality of life. Both drugs did not differ in the proportion of patients reporting dizziness, somnolence and weight gain as a side effect (low quality evidence). Compared with amitriptyline, more people experienced side effects and left the study due to side effects with quetiapine (low quality evidence). No serious side effects with either drug were reported (low quality evidence). We found no relevant study with other antipsychotics than quetiapine in fibromyalgia.
Cryotherapy, usually using liquid nitrogen, is often used for the treatment of warts, but it is less convenient, more painful, and also more expensive. One study suggested that there is evidence that cryotherapy is better than SA for warts on the hands, but when we combined this study with our other results, we were unable to confirm this. We found that more aggressive cryotherapy appears to be more effective than gentle cryotherapy, but with an increased risk of adverse effects, such as pain, blistering, and scarring. We only looked at information from clinical trials of cryotherapy and not over-the-counter freezing treatments for warts, so we cannot say if these are as effective. During the production of the last version of this review, duct tape had gained favour as it is a safe and simple treatment that is easy to apply; however, the trial on which this was based was relatively small. In this updated review, we found two further trials of duct tape that suggested that this treatment is not as effective as first thought. Other treatments covered by this review include 5-fluorouracil, dinitrochlorobenzene, intralesional bleomycin, intralesional interferon, photodynamic therapy, and intralesional antigen. None of these treatments are used commonly, even by skin specialists, and there is much less evidence for their effectiveness. The limited available evidence we do have suggests that some of these treatments may be effective and could therefore be used for warts that have not responded to simpler, safer treatments, such as salicylic acid or cryotherapy. Overall, providing a useful idea of 'what works' from such a wide range of studies was difficult as many studies were of poor quality.
In this analysis, we reviewed the currently available evidence to determine the impact of garlic on cardiovascular events and mortality in patients with hypertension. Based on data from two randomized controlled trials that compared garlic to placebo in patients with hypertension it appears that garlic may have some blood pressure lowering effect, as compared to placebo but the evidence currently available is insufficient to determine whether garlic provides a therapeutic advantage versus placebo in terms of reducing the risk of cardiovascular morbidity and mortality. Data on the safety of garlic, as a therapeutic entity, in this population is also lacking. More (and large enough) trials comparing several doses of garlic with placebo are needed to detect possible differences in mortality, serious adverse events, and cardiovascular morbidity.
Previous research on animal and physiological models suggests that antioxidant supplements have beneficial effects that may prolong life. Some observational studies also suggest that antioxidant supplements may prolong life, whereas other observational studies demonstrate neutral or harmful effects. Our Cochrane review from 2008 demonstrated that antioxidant supplements seem to increase mortality. This review is now updated. The present systematic review included 78 randomised clinical trials. In total, 296,707 participants were randomised to antioxidant supplements (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Twenty-six trials included 215,900 healthy participants. Fifty-two trials included 80,807 participants with various diseases in a stable phase (including gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified diseases). A total of 21,484 of 183,749 participants (11.7%) randomised to antioxidant supplements and 11,479 of 112,958 participants (10.2%) randomised to placebo or no intervention died. The trials appeared to have enough statistical similarity that they could be combined. When all of the trials were combined, antioxidants may or may not have increased mortality depending on which statistical combination method was employed; the analysis that is typically used when similarity is present demonstrated that antioxidant use did slightly increase mortality (that is, the patients consuming the antioxidants were 1.03 times as likely to die as were the controls). When analyses were done to identify factors that were associated with this finding, the two factors identified were better methodology to prevent bias from being a factor in the trial (trials with ‘low risk of bias’) and the use of vitamin A. In fact, when the trials with low risks of bias were considered separately, the increased mortality was even more pronounced (1.04 times as likely to die as were the controls). The potential damage from vitamin A disappeared when only the low risks of bias trials were considered. The increased risk of mortality was associated with beta-carotene and possibly vitamin E and vitamin A, but was not associated with the use of vitamin C or selenium. The current evidence does not support the use of antioxidant supplements in the general population or in patients with various diseases.
Randomised controlled trials were therefore developed to test the hypothesis that nicotine patches can induce remission of a flare of ulcerative colitis. This review provides evidence that transdermal nicotine is superior to placebo (fake patch) for the treatment of active ulcerative colitis. However, patients treated with transdermal nicotine were significantly more likely to experience side effects than patients receiving placebo or standard medical therapy. Its use is therefore limited in some patients. The review did not identify any significant advantage for transdermal nicotine therapy compared to standard medical therapy.
We identified and included one study, which compared steroids with placebo (dummy pill) in 49 newborns. The steroids were given to babies by inhalation. We found no ongoing studies. The evidence is up to date as of February 2019. Steroids did not improve lung function or reduce the need for breathing support. Overall, we are uncertain as to whether steroids have an important effect on rapid breathing because the results are imprecise and based on only one small study.
We searched scientific databases for randomised trials in which people scheduled for CABG (with or without valve surgery) were randomly assigned to receive RIPC or sham intervention before surgery. The evidence is current to May 2016. We did not identify any source of bias related to the funding of included studies. We identified 29 studies involving 5392 participants (mean age = 64 years, age range 23 to 86 years, 82% male). RIPC does not improve clinical outcome in people undergoing CABG with or without valve surgery (measured as a composite endpoint including all-cause mortality, non-fatal myocardial infarction or any new stroke, or both, assessed at 30 days after surgery, moderate-quality evidence). There is moderate-quality evidence that RIPC reduces the amount of cardiac troponin T release measured at 72 hours and measured as AUC (72 hours). There is moderate-quality evidence that cardiac troponin I release measured at 48 hours and 72 hours after surgery is lower in the RIPC group than in the control group. Regarding troponin T measured at 48 hours and troponin I measured as AUC 72 hours after surgery there was no difference between groups (low- and moderate-quality evidence). However, this effect on biomarkers does not result in improved clinical outcome. We used reliable methods to assess the quality of the trial evidence. The quality of the evidence of key outcomes ranged from moderate to low quality due to the presence of moderate or high statistical heterogeneity, imprecision of results or due to limitations in the design of individual studies.
We carried out a wide search of medical databases for trials in which participants were randomly assigned to plasma exchange or no treatment except supportive care. We found six trials, which included 649 participants in total. All six trials compared plasma exchange with supportive treatment. All were at low risk of bias, except that participants and their carers were aware of the treatment given (they were not blinded). Two additional studies compared different numbers of plasma exchange and could not be included in the analysis but are discussed. Plasma exchange speeded improvement from GBS. It did not cause harm apart from being followed by a probable slight increase in risk of relapse. Despite this, plasma exchange probably increases the chance of complete muscle strength recovery after one year. No new trials have been done since the first publication of this review in 2001. However trials have been done comparing plasma exchange with intravenous infusion of human immune globulin (the antibody portion of plasma). These trials are included in another Cochrane review and show the effects of the two treatments are similar. The evidence is up to date to 18 January 2016.
Four randomised trials were included in the review. These involved a total of 278, mainly adult, participants with 283 mallet finger injuries. The methods of all four trials were flawed leading to concerns about bias. There was no pooling of data. Three trials compared different types of finger splints versus a standard Stack splint. One trial found less treatment failure in participants treated with a perforated custom-made splint. A second trial found there were fewer complications in participants treated with a padded aluminium-alloy malleable finger splint. However, the incidence of treatment failure was similar in the two treatment groups of this trial. The third trial evaluated the Abouna splint and found a similar incidence of treatment failure in the two groups. However, the Abouna splint often needed replacing due to disintegration of its rubber cover and rusting of the exposed wires and was also less popular with participants. The fourth trial in the review found no significant differences between participants whose mallet finger was treated with Kirschner wire fixation and those with a Pryor and Howard splint. Similar numbers had complications in the two groups. The review concluded that there was not enough evidence to show which is the best way to treat mallet finger injury. It noted, however, that splints used for prolonged immobilisation should be robust enough for everyday use.
The focus of this review is routine early pregnancy ultrasound (before 24 weeks). We included 11 randomised controlled trials involving 37,505 women. Early ultrasound improved the early detection of multiple pregnancies and improved gestational dating, which may result in fewer inductions for post maturity. The detection of fetal malformation was addressed in detail in only two of the trials. There was no evidence of a significant difference between the screened and control groups for perinatal death. Results do not show that routine scans reduce adverse outcomes for babies or lead to less health service use by mothers and babies. Long-term follow-up of children exposed to scans before birth did not indicate that scans have a detrimental effect on children's physical or intellectual development. Studies were carried out over three decades and technical advances in equipment, more widespread use of ultrasonography, and increased training and expertise of operators may have resulted in more effective sonography.
We searched for studies on 13 August 2019, and found two that met our inclusion criteria. Our main focus was to learn if video counselling delivered individually or to a group could help people quit smoking and to learn how it compared with other types of support to help people quit. We also studied the effect of real-time video counselling on the number of times people tried to quit, the number of sessions they completed, their satisfaction with the counselling, their relationship or bond with the counsellor and the costs of using video communication to help people quit smoking. Both studies took place in the USA, and included people from rural areas or women with HIV. Both studies gave one-to-one video sessions to individuals. There were eight video sessions in one study and four video sessions in the other study. Both studies compared video counselling to telephone counselling and looked at whether people quit smoking, the number of sessions they completed and their satisfaction with the programme. One study examined the number of times people tried to quit and one study looked at the relationship or bond with the counsellor. It is unclear how video counselling compares with telephone counselling in terms of helping people to quit smoking. People who used video counselling were more likely than those who used telephone counselling to recommend the programme to a friend or someone in their family, but we found no differences in how satisfied they were, the number of video or telephone sessions completed, whether all sessions were completed and in the relationship or bond with the counsellor. We rated the quality of the evidence for smoking cessation to be very low. There were only two studies, and the limitations in these studies made it difficult to draw reliable conclusions about whether video counselling can help people to quit smoking. This should be taken into account when looking at these findings.
This evidence is current up to July 2018. We included 26 studies involving 23,499 participants. These studies assessed the effects of ezetimibe plus other lipid-lowering drugs versus lipid-lowering drugs alone for heart disease. The participants were adults, and most of them had been diagnosed with coronary heart disease. Ezetimibe with statins probably reduces the risk for combined outcome of death due to heart disease, heart attack or stroke, but the benefit is moderate. However, adding ezetimibe to statin or fenofibrate have little or no effect on death from any cause. Treatment with ezetimibe and statin probably reduces the risk for non-fatal heart attacks and non-fatal stroke. Adding ezetimibe to statin or fenofibrate probably have little or no effect on heart-related death. Ezetimibe with statins might reduce the need for coronary revascularisation (the restoration of an adequate blood supply to the heart) by means of surgery. In terms of safety, we do not have enough evidence to know whether ezetimibe increases or decreases side-effects (e.g. liver injury, muscle pain, cancer, gallbladder-related disease and discontinuation). The analysis of blood lipids revealed that the addition of ezetimibe statin or fenofibrate therapy might further reduce the levels of blood lipids, including low-density lipoprotein cholesterol ('bad' cholesterol), total cholesterol and triglycerides, and likely increased the level of high-density lipoprotein cholesterol ('good' cholesterol). None of the included studies reported on health-related quality of life. There is a lack of evidence supporting the use of ezetimibe monotherapy for the prevention of heart disease, and this topic requires further investigation. The quality of evidence ranged from high to very low across the outcomes.
We included data from three trials of low to moderate risk of bias of 327 children with AOM. One trial (219 children) compared paracetamol versus ibuprofen versus a dummy drug in children with AOM. In this trial, all children also received antibiotic treatment and those with fever > 39 °C may have received paracetamol in addition to the studied treatments. Two other trials compared the effects of paracetamol versus ibuprofen versus ibuprofen plus paracetamol in children with fever and patients with respiratory tract infections, respectively. The authors of these two trials provided crude subgroup data on children with AOM (26 and 82 children, respectively). In one trial, paracetamol, ibuprofen and a dummy drug were supplied by a pharmaceutical company (Ethypharm). No further details were provided about the role of this company in the design, conduct, analysis, or reporting of the trial. The other two trials were funded by governmental (non-commercial) grants. In one trial the drugs were purchased from and provided by two companies (Pfizer and DHP Investigational Medicinal Products) which had no role in the design, conduct, analysis, or reporting of the trial. Very limited information was available to assess how useful painkillers are for relieving children's pain due to AOM. We found that both paracetamol and ibuprofen when used alone were more effective than a dummy drug in relieving ear pain at 48 hours (25% of children receiving a dummy drug had residual pain at 48 hours versus 10% in the paracetamol group and 7% in the ibuprofen group). The adverse events reported in the trials did not significantly differ between children treated with either paracetamol, ibuprofen or dummy drug, but this finding should be interpreted cautiously, given there were few participants, and infrequent occurrence of adverse events. We found insufficient evidence of a difference between paracetamol and ibuprofen in relieving short-term (at 24 hours, 48 to 72 hours and 4 to 7 days) ear pain in children with AOM. We could not draw any firm conclusions on the effects of ibuprofen plus paracetamol versus paracetamol alone in relieving ear pain in children with AOM mainly because of the very limited number of participants (very small sample size). Evidence quality for ear pain relief at 48 hours for the comparisons paracetamol versus a dummy drug and ibuprofen versus a dummy drug was judged low (study limitations and questions about the applicability of evidence affected our confidence in the results); the quality of evidence for adverse events was judged very low (study limitations, small sample size and infrequent occurrence of adverse events affected our confidence in the results). Evidence quality for ear pain relief at 48 to 72 hours for the comparison ibuprofen versus paracetamol was judged low (study limitations and questions about the applicability of evidence affected our confidence in the results); the quality of evidence for ear pain relief at 24 hours and four to seven days was judged very low (study limitations and very small sample size affected our confidence in the results). Evidence quality for all outcomes in the trials comparing ibuprofen plus paracetamol versus paracetamol alone was very low (study limitations and very small sample size affected our confidence in the results).
The objectives of this review were to assess the effects of the sequential combination of glucocorticosteroids and interferon compared to interferon alone in the treatment of chronic hepatitis B. Glucocorticosteroid pretreatment was associated with a significantly higher frequency of loss of hepatitis B markers (HBeAg and HBV DNA), but had no significant effect on clinical outcomes.
We searched for evidence in February 2018, and found three randomised controlled trials, involving over 26,000 women. Two trials contributed data to our analyses; one study did not provide data for any of the outcomes of interest in this review. All of the trials took place in hospital settings. Two trials took place in India, the other was conducted in 13 different European countries. The trials examined different methods of estimating blood loss. One trial (conducted in 13 European countries, involving over 25,000 women) compared the use of a calibrated drape (direct estimation) to visual estimation (indirect estimation). Moderate-quality evidence showed there was probably little or no difference between the methods for the risk of women developing serious conditions (e.g. failure to form clots, poor functioning of the liver, kidneys, and brain, admission to intensive care); their need for blood transfusion; the use of fluids to maintain their blood pressure; or the use of drugs to help their uterus contract to stop the bleeding. The trial did not report the number of women who had anaemia after birth, blood loss of at least 500 mL, or infection. One trial (conducted in India, involving 900 women) compared the use of a calibrated drape (direct estimation) to weighing and measuring blood and blood-soaked materials (indirect method). High-quality evidence showed that calibrated drapes were better than measuring the blood and blood-soaked materials at detecting blood loss of at least 500 mL. Low-quality evidence showed there may be little or no difference between methods in the need for blood transfusion or fluids to maintain blood pressure. High-quality evidence showed little or no difference in the use of drugs to help the uterus contract in order to stop bleeding. The trial did not report the number of women who had anaemia after birth or infection, or the risk of developing serious conditions (such as failure to form clots, poor functioning of the liver, kidneys, and brain, or being admitted to intensive care). There was insufficient evidence to support the use of one method over another to estimate blood loss after vaginal birth. There is a need for high quality trials that measure important outcomes, such as those listed in this review.
This review has tried to do that by examining research about family-centred care. We looked for randomised trials of family-centred care interventions for children aged 0-12 years, in hospitals. We assessed potentially-relevant studies against criteria that identify important parts of family-centred care. Despite extensive searching we identified only one moderate-quality study (Bolton 2004) for inclusion. This study, from a doctoral thesis, showed that the family-centred care model had a positive effect on the adequacy of children's care, parental satisfaction, and costs. For other indicators such as clinical outcomes and children's behaviour there was no significant difference between the family-centred care model and standard inpatient care. There were no harms reported. In this searches for this update, we also found 25 qualitative studies which described aspects of family-centred care, and a review of these will be published by the Joanna Briggs Institute. Our main conclusion from this Cochrane review update, however, is that further, rigorous research is needed to assess the effects of family-centred care on children's experience of hospitalisation, as well as on their parents, hospital staff, and service delivery outcomes such as costs.
We found four small trials that provided data on 358 women. We estimated that the risk of bias was low for women enrolled in the study and the researchers as far as knowing if they were in the treatment group or the control (or placebo) group. It was unclear if there was a risk of bias for how the decisions were made to for women to be in the treatment or control/placebo groups, for those looking at the results and if all the results were reported. Two trials looked at medication compared with placebo or no treatment. One study examined the effect of a medication(sucralfate) in comparison to advice on dietary and lifestyle choice. One trial evaluated acupuncture versus no treatment. Women who received medication reported complete relief from heartburn more often than women receiving no treatment or placebo, or women who received advice on diet and lifestyle choices (moderate quality of evidence). We found no difference in partial relief of heartburn nor in side effects between the treatment groups (very low quality of evidence). We also found women who received acupuncture reported improved quality of life in terms of improved ability to sleep and eat, and no difference in the rate of side effects compared to women who received no acupuncture, From the little evidence there is, medication seems to help relieve heartburn but there is not enough data to say which medication is best. Acupuncture seems to help women to eat and sleep better when troubled with heartburn. Further research is needed to fully evaluate the effectiveness of interventions for heartburn in pregnancy. Future research should also address other medications such as histamine 2-receptor antagonists, promotility drugs, proton pump inhibitors, and a raft-forming alginate reflux suppressant in treatment of heartburn in pregnancy. More research is needed on acupuncture and other complimentary therapies as treatments for heartburn in pregnancy. Future research should also consider any adverse outcomes, maternal satisfaction with treatment and measure pregnant women's quality of life in relation to the intervention.
We undertook a comprehensive search to identify relevant studies. We found 3,072 references, but only one study that met our criteria. The study was performed in 2003-2004 in Tanzania. Pregnant women in the intervention group were provided with a letter inviting their male partners to accompany them to their next visit, in which they were offered voluntary HIV counselling and testing (VCT) together or separately. Women in the control group received the VCT individually during their first visit. The proportions of women that received VCT and collected their HIV test results were significantly lower in the intervention group than in the control group. Most of the women in the intervention group did not return to the clinic for the subsequent visit and most of those that returned accompanied refused to receive VCT together with their male partners. The invitation letter had a negative impact on the PMTCT uptake in that setting. We urgently need more studies assessing different interventions to improve male engagement in PMTCT to identify the most successful approach for women to safely access health care for their own health and to deliver HIV negative children.
Four studies, involving 414 participants, were included in this review. The trials lasted between two months and 12 months. One study was conducted in the UK, the other three in the USA. All studies compared emotional disclosure writing versus non-stressful writing. Three studies were conducted in adult participants and one in adolescents. The average age of participants ranged from 14 to 43 years. In all trials, most of the participants were female. There is no evidence to support that written emotional disclosure is helpful in improving lung function or symptoms in patients with asthma. However, disclosure may be beneficial for patients' perceptions of their own asthma control. Based on evidence obtained from the studies, we are not able to draw conclusions about the role of written emotional disclosure in quality of life, psychological well-being, asthma medication use or use of healthcare facilities for asthma-related problems. Better designed studies are necessary to determine the effects of written emotional disclosure for patients with asthma. Our interpretation of the studies was limited by variation in study settings, topics of the non-stressful writing exercise and study duration. The evidence presented in this review is generally of low quality. This summary was current to January 2014.
People with hypercholesterolemia have a higher risk of developing coronary artery disease, heart attacks, and stroke. Chinese herbal medicines have been commonly used and studied as cholesterol-lowering agents. To evaluate the effects of various herbal formulations (including single herbs, Chinese proprietary medicines, and mixtures of different herbs) for treating hypercholesterolemia, this review examined 22 randomized controlled trials of five different Chinese herbal medicines. The trials lasted from one to six months (average 2.3 months) and involved 2130 participants. There were no data on cardiovascular events and death from any cause. One trial each reported on well-being (no significant differences) and economic costs . No serious adverse events were observed. The available evidence suggests that several herbal medicines showed some cholesterol-lowering effect. However, due to considerable limitations in the quality of the included trials, further higher-quality and rigorously performed studies are required before any confident conclusions can be reached about the effects of Chinese herbal medicines for hypercholesterolemia.
We ran an electronic search in November 2015 for trials that randomised people with serious mental illness to receive either oral health advice, monitoring, or standard care. Three studies meeting the required standards were found and are included in this review. Key results The data available in the included trials suggests that participants receiving oral health education had statistically better plaque index scores than those not receiving oral heath education, but what this actually means clinically is unclear. The trials provided no information about such important issues as number of visits made to dentists or how many times teeth were brushed each day and if there were any potential adverse effects of oral health education. The review authors suggest that although there is currently no real evidence available from trials, it would make sense to follow the guidelines and recommendations put forward by the British Society for Disability and Oral Health working group regarding oral health care for people with mental health problems. Quality of the evidence The quality of evidence in the small number of trials available was low to moderate. There is currently a lack of good-quality evidence available from trials to aid in decision-making about the overall effectiveness of oral health advice for people with serious mental illness. More good-quality trials are required to gather better and more concrete evidence. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/
We searched scientific databases for clinical studies comparing ¹²³I-MIBG or 18F-FDG-PET imaging, or both, with microscopic examination of tissue suspected of neuroblastoma (histopathology). The evidence is current up to 11 September 2012. We identified 11 eligible studies including 621 children that fulfilled our inclusion criteria: children < 18 years old with a neuroblastoma and ¹²³I-MIBG or 18F-FDG-PET imaging or both. All studies included proven neuroblastoma. All 11 included studies had methodological limitations. Only one included study provided data on specificity (the ability of a test to correctly classify an individual as 'disease-free') and therefore we could not perform all of the planned analyses. When compared to histopathological results the sensitivity (the ability of a test to correctly classify an individual person as 'diseased') of ¹²³I-MIBG imaging varied from 67% to 100% in patients with histologically proven neuroblastoma. This means that in 100 children with proven neuroblastoma ¹²³I-MIBG imaging will correctly identify 67 to 100 of the neuroblastoma cases. Only one study, that reported on a lesion level, provided data to calculate the specificity (the ability of a test to correctly classify an individual as 'disease-free'): 68% in 115 lesions. This means that of 100 disease-free lesions in patients with proven neuroblastoma ¹²³I-MIBG imaging will correctly identify 68 lesions. So, in about 10% of the cases the neuroblastoma is not visible on ¹²³I-MIBG imaging (false negative results). For these cases, it is advisable to perform an additional test like 18F-FDG-PET imaging, but to be certain of its clinical value, more evidence is needed. Only one included study reported on false positive findings. This means that ¹²³I-MIBG imaging and 18F-FDG-PET imaging incorrectly identified neuroblastoma lesions in patients which might result in wrongly classifying a patient with metastatic disease. It is important to keep in mind that false positive findings can occur, although more research is needed before definitive conclusions can be made. We could not determine the diagnostic accuracy of 18F-FDG-PET imaging, in case the neuroblastoma was incorrectly not identified with ¹²³I-MIBG, due to limited data. Also, we could not calculate the diagnostic accuracy of 18F-FDG-PET imaging for detecting a neuroblastoma and compare this to ¹²³I-MIBG imaging because of the limited available data.
We included in the review controlled trials from 1966 to February 2015 involving participants of all ages needing rapid intubation using rocuronium and succinylcholine . The minimum dose of rocuronium given was 0.6mg/kg and succinylcholine was 1mg/kg. We have combined the results of 50 trials, with a total of 4151 participants, which compared the effectiveness of succinylcholine versus rocuronium on intubation conditions. No major side effects from use of the drugs were reported. We have found that rocuronium is slightly less effective than succinylcholine for creating excellent and acceptable intubation conditions. Rocuronium should therefore only be used as an alternative to succinylcholine when it is known that succinylcholine should not be used and a more prolonged intubation is expected. The level of evidence is of moderate GRADE due to imperfect study designs and varying techniques used across trials .
In September 2016 we searched for randomised controlled trials (RCTs) that investigated whether ultrasound helps to heal or improves the symptoms of venous leg ulcers. We found 11 trials involving a total of 969 participants. The average (mean) age of participants ranged from 59 years to 70 years. The proportion of female participants ranged from 55% to 79%. Eight studies compared ultrasound with use of no ultrasound for venous leg ulcers and the other three compared ultrasound with sham ultrasound. Seven out of the eleven studies were at high risk of bias and we could not assess the potential bias in three studies due to poor reporting. One study was at low risk of bias. The trials were all different, for example in their duration of follow-up (three weeks to 12 months), and the strength of the ultrasound waves used (high or low frequency ultrasound). It is not clear from this evidence whether ultrasound (high or low frequency) increases the healing of venous leg ulcers. The results of one study (337 participants) suggest that high-frequency ultrasound may be associated with more adverse events such as pain and skin redness (moderate quality evidence). The two studies that evaluated low-frequency ultrasound did not report whether participants experienced side effects. It is also uncertain whether either high- or low-frequency ultrasound affects participants' quality of life. Most of the studies we found did not have many participants, had short follow-up times and had weaknesses of study design that meant they were quite likely to give a misleading result. We consider the available evidence to be low quality due to these risks of bias. This plain language summary is up to date as of September 2016.
This review of two randomized trials (RCTs) showed that continuous ultrasound applied in water to the dorsal and palmar aspects of the hand increased grip strength as compared with placebo. This benefit was not evident with combined therapy (exercise, wax bath, faradic hand baths). Ultrasound also produced a borderline increase in wrist dorsal flexion, decreased morning stiffness, and reduced the number of swollen and painful joints. The conclusions are limited by few studies, small sample size and limitations in study methodology.
This review contains 21 RCTs conducted up to July 2014 that included 2082 participants with heavy menstrual bleeding. Evidence obtained is current to January 2015. Almost all the studies assessed the effects of the LNG IUS and conclusions refer only to this device. The LNG IUS was more effective in reducing heavy menstrual bleeding and improving quality of life than oral medication. Satisfaction with treatment was not assessed in enough trials to know whether this was better with LNG IUS. The evidence suggested that the LNG IUS and techniques used to remove the inner lining of the womb were similarly effective at reducing heavy menstrual bleeding and improving quality of life and satisfaction and the two treatments had similar failure rates. The LNG IUS caused higher rates of some side effects, such as breast tenderness, bloating, weight gain and ovarian cysts, but this did not seem to cause women to stop taking their treatment. The LNG IUS was not as effective as hysterectomy in reducing menstrual blood loss but improvements in quality of life were similar. Although many women trying the LNG IUS eventually went on to have a hysterectomy for their heavy menstrual bleeding, the LNG IUS appeared to have lower overall costs than either endometrial ablation or hysterectomy. Many of the trials in this review were small (<100 participants) and some were at high risk of bias. Ratings for the overall quality of the evidence for each comparison ranged from very low to high. Limitations in the evidence included inadequate reporting of study methods and inconsistency. One large trial compared the LNG IUS with hysterectomy over a 10-year period and a number of other trials made assessments two years after starting treatment, so we have some information on the long-term effects of treatments. Future research needs to measure satisfaction.
We searched for studies up to Novemeber 2019 that compared different ways of managing the drainage of fluid collected in the abdomen of women with gynaecological cancer (cancer that starts in a woman's reproductive organs). The original 2010 review found no relevant studies. This updated review included one randomised controlled trial (RCT: a type of study in which people are randomly assigned to receive different treatments) involving 245 women that compared drainage combined with catumaxomab (a medicine used to treatment malignant ascites) versus drainage alone. However, the results were insufficient to assess the difference between these treatments. Although women receiving drainage combined with catumaxomab had better quality of life (the general well-being of a person) for longer compared to drainage alone, we are very unsure of this evidence due to the small number of participants and trials. There were some side effects in the drainage plus catumaxomab group (e.g. pain, low white blood cell count), but they were not well reported. At present, there is insufficient data regarding the best management of drainage for malignant ascites among women with gynaecological cancer. The evidence is current to 4 November 2019.
We examined evidence about benefits and risks from studies that compared carotid artery stenting to carotid surgery in people who already had symptoms caused by carotid stenosis (stroke, transient ischaemic attack (TIA), or ocular (eye) symptoms) or in people who have never experienced symptoms. The studies had to be randomised; that is, the decision whether people were treated by stenting or surgery had to be made randomly and neither they nor the researchers were able to decide which treatment they received. This was to make the comparison as unbiased, or fair, as possible. We searched for studies up to August 2018. We assessed the quality of all the studies we included. This review included 22 studies involving 9753 participants. In people who have already experienced symptoms from a narrowing in the carotid artery, stenting caused more strokes or deaths around the time of the procedure than surgery. This was especially true for people over the age of 70 years. After the initial procedure, both treatments were equally effective in preventing stroke or death in the long term. In people who had never experienced symptoms from the carotid stenosis, both carotid artery stenting and surgery carried a similar risk of stroke or death in the short and long term, although the certainty of the evidence in these people was only moderate and the results should be interpreted with caution. In general, the quality of the evidence was high. The main factor reducing our confidence in the evidence was in studies comparing both treatments in people who had never experienced symptoms from the narrowing in the carotid artery. For these people, more studies are needed to draw firm conclusions about the risks and benefits of stenting compared to surgery.
We found six studies involving 535 healthcare practitioners. The studies examined strategies encouraging practitioners to use EHI when caring for patients. We measured practitioners' use of EHI by counting the number of times they logged onto it; by measuring whether or not practitioners' followed the guidance provided by EHI; and by improvements experienced by patients. The studies compared the following strategies: EHI versus printed information (one study); EHI on a "mobile" (e.g. laptop computer) versus a stationary, desktop computer (one study); EHI presented with different search interfaces (an interface is what a user sees when accessing an online resource, think of Google versus Yahoo) (one study); and EHI provided with training (three studies). The results of this review showed that when provided with a combination of EHI and training, practitioners used the information more often. Two studies measured doctors' use of electronic treatment guidelines, but showed that the electronic aspect of the guidelines did not mean that doctors followed the guidelines. This review provided no information on whether more frequent use of EHI translated into improved clinical practice or whether patients were better off when doctors or nurses used health information when treating them. All included studies were randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups), which are considered high-quality sources of evidence. However, three of the four comparisons that we examined were supported by only one study each and single studies do not typically produce high-quality evidence. Overall, we rate the body of evidence in this review as low quality.
We included six studies which were small with 310 infants, of whom 297 were included for analysis. The studies were short (10 to 42 days), and generally poor quality. Studies were in different countries, and, where stated, in paediatric clinics. Where stated in three studies, 60% were boys (144 boys among 241 infants). Most infants were aged under seven months; two were aged seven and 12 years. ISD severity where described was mild to moderate; one study included two participants with severe ISD. The treatments tested included: oral biotin (a B group vitamin) compared to placebo; trademarked creams or gels compared to placebo (or a control group); and steroid lotion or ointment compared to licochalcone (Chinese liquorice) cream and eosin (a red staining agent). Four studies had support from pharmaceutical companies: in three studies, a company supplied the intervention product; a company assisted with statistical analysis in one study; one employed a study author; and one had authors who were consultants to the pharmaceutical company. The evidence is current to 22 May 2018. Two trials assessed oral biotin versus placebo. One study only assessed duration of rash, and the other only reported that there was no differences between groups. Thus, it was unclear which treatment was more effective. In the two trials assessing trademarked skin products versus placebo, there was similar improvement in severity between Promiseb cream (96%) and placebo (92%). One trial assessed lactamide MEA gel plus shampoo versus shampoo only. Reduction of surface area covered and severity of rash was slightly higher in the gel group (81.4%) compared with shampoo only (70.2%). When comparing hydrocortisone 1% lotion with licochalcone 0.025% lotion in one study, cure rates, as a sign of severity, were also similar (95.8% with hydrocortisone versus 97.1% with licochalcone). Reduction in body surface area affected was similar when comparing flumethasone pivalate 0.02% ointment (9%) versus eosin 2% aqueous solution (7%). Only two trials reported side effects, including one case of increased skin redness with licochalcone, while in the study comparing lactamide MEA gel plus shampoo versus shampoo only there were no specific side effects reported. No studies measured improvement in quality of life. The quality of the evidence was downgraded to very low for all outcome measures in this review due to serious concerns with how the studies were conducted (risk of bias), how the outcomes were measured and reported, differences between the assessed treatments, and the small number of participants included. Thus, we cannot be certain of their accuracy.
We found nine randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) comparing the insulin analogues, insulin lispro and insulin aspart, to regular human insulin delivered to 2693 participants. The people in the included studies were monitored (called follow-up) for between 24 and 52 weeks. This evidence is up-to-date as of 15 April 2015. According to our analysis, short-acting insulin analogues were slightly better than regular human insulin regarding long-term glycaemic control (where blood glucose is at controlled levels) and showed similar episodes of low blood sugar (called hypoglycaemia), especially with regard to severe (night-time) hypoglycaemia. We found no information on late diabetes complications such as problems with the eyes, kidneys or feet. The studies did not report costs and they were too short to investigate death from any cause reliably. We also found no clear evidence for a marked effect of insulin analogues on the health-related quality of life (which is physical, mental, emotional and social health). The quality of the included studies was low or very low, mainly because none of the studies was carried out in a blinded way (where healthcare professionals and participants do not know which treatment they received) so that risk of bias, especially for outcomes such as hypoglycaemic episodes, was present in all of the studies. Furthermore, several studies showed inconsistencies in the reporting of methods and results.
We searched for evidence in November 2017 and identified six randomised trials. This review included six trials that randomly assigned women to a policy of interventionist management or expectant management when presenting with severe pre-eclampsia before 34 weeks of pregnancy. A total of 748 women were included in these six trials. Babies born to women allocated to an interventionist approach were probably more likely to experience adverse effects such as bleeding in the brain (intraventricular haemorrhage). They may also have been more likely to require ventilation, have a longer stay in the neonatal unit, have a lower gestation at birth in days, and weigh less at birth than those babies born to women allocated to an expectant management approach. There was insufficient evidence for reliable conclusions about the effects on perinatal deaths. Babies whose mothers had been allocated to the interventionist group were no more likely to be admitted to neonatal intensive care. There were no maternal deaths in the two studies that reported this outcome. The evidence was very low-quality for the outcome of fits or convulsions (eclampsia), or of fluid in the lungs (pulmonary oedema), and so it was uncertain whether interventionist care made any clear difference to the mothers' health. Evidence from two studies suggested little or no clear difference between the interventionist and expectant care groups for a severe form of pre-eclampsia, which affects the liver and blood clotting, called HELLP syndrome, which stands for haemolysis (breakdown of red blood cells), elevated liver enzymes (a sign of liver damage), and low platelets (platelets help the blood to clot). None of the studies reported on the incidence of stroke in the mother. With the addition of data from two studies for this update, there was now evidence to suggest that interventionist care probably made little or no difference to the caesarean section rate. In the absence of an over-riding maternal or fetal indication for immediate delivery, delay may be more beneficial for the baby. However, there were insufficient data to enable us to draw reliable conclusions about the comparative effects on most outcomes for the mother, and hence the maternal safety of an expectant approach. This evidence was based on data from only six trials. Further large trials with long-term follow-up of the children are needed to confirm or refute whether expectant care is better than early delivery for women who suffer from severe pre-eclampsia before 34 weeks of pregnancy.
This systematic review uses the data of individual patients from eight and published data from another six randomized controlled trials. We found that the administration of chemotherapy before surgery leads to longer survival in patients with adenocarcinoma of the esophagus, the junction between esophagus and stomach, and the stomach. The findings suggest that patients whose tumor is in the junction between esophagus and stomach and younger patients benefit most from the chemotherapy. Moreover, the addition of radiation to the chemotherapy seems to yield an additional advantage to patients, at least in tumors of the esophagus and the junction between esophagus and stomach. Chemotherapy before surgery does not increase the risk of suffering a complication during or after surgery.
We included 68 Cochrane systematic reviews on various stages of the ART cycle. All were of high quality. We included in the overview reviews of in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). We did not include reviews of intrauterine insemination (placing sperm inside a woman's uterus to facilitate fertilisation) or ovulation induction (stimulation of ovulation by medication). This overview provides the most up-to-date evidence from randomised controlled trials on ART cycles. The overview is up-to-date to May 2018. The reviews identified 38 interventions that were effective (n = 23) or promising (n = 15), and they identified 19 interventions that were ineffective (n = 2) or possibly ineffective (n = 17). For 15 interventions, the reviews were unable to draw conclusions owing to lack of evidence. Use of evidence from this overview to guide clinical practice should help to improve live birth rates and reduce rates of multiple pregnancy, cycle cancellation, and ovarian hyperstimulation syndrome. All included reviews were of high quality. The quality of the evidence for specific comparisons ranged from very low to high.
In this review, we analysed studies which investigated a wide variety of interventions. Our results suggested that bupropion (an antidepressant medication previously shown to be effective for smoking cessation) helps patients with schizophrenia to quit smoking. The effect was clear at the end of the treatment and it may also be maintained after six months. Patients who used bupropion in the trials did not experience any major adverse effect and their mental state was stable during the treatment. Another medication, varenicline (a nicotine partial agonist which has been shown to be an effective intervention for smoking cessation in smokers without schizophrenia), also helps individuals with schizophrenia to quit smoking at the end of the treatment. However, this evidence is only based on two studies. We did not have sufficient direct evidence to know whether the benefit of varenicline is maintained for six months or more. In addition, there has been ongoing concern of potential psychiatric adverse events including suicidal ideas and behaviour among smokers who use varenicline. We found that two patients, among 144 who used varenicline, had either suicidal ideas or behaviour. Smokers with schizophrenia who receive money as a reward for quitting may have a higher rate of stopping smoking whilst they get payments. However, there is no evidence that they will remain abstinent after the reward stops. There was too little evidence to show whether other treatments like nicotine replacement therapy and psychosocial interventions are helpful.
Animal and cell culture studies have produced evidence that inflammatory processes may be involved in the pathogenesis of AD. As a result, agents such as ibuprofen have been proposed for the treatment of people with AD. Although ibuprofen is better tolerated overall than some other NSAIDs, such as indomethacin, no randomized controlled trials investigating the efficacy of this drug for treatment of people with AD have been published. One such a trial is underway. The use of ibuprofen for the treatment of AD cannot at present be recommended.
Six studies randomising 596 healthy kidney donors to either keyhole or open surgery, found keyhole surgery to be associated with less pain for the donor but had similar numbers of complications that can require further treatment or surgery or both. Donor kidneys that were obtained using the keyhole surgical technique were deprived of nutrients for longer periods of time than kidneys obtained for transplant using open surgery, but this does not appear to have any short-term consequences.
Forty-nine trials met the inclusion criteria. Six trials involving 497 participants were included to study efficacy, and compared acetylcysteine or carbocysteine to placebo. Thirty-four trials (including the previous six) were eligible to study safety and involved 2064 paediatric patients. The results of this review suggest actual but limited efficacy of acetylcysteine and carbocysteine (e.g. reduction of cough at day seven) and good overall safety (except for rare mild gastrointestinal side effects) among children older than two years of age. However, the number of participants included was limited and the methodological quality was questionable. These results should also take into consideration the fact that acetylcysteine and carbocysteine are prescribed for self limiting diseases (for example, acute cough, bronchitis). In children younger than two years, and given strong concerns about safety (increased instead of decreased bronchial secretions), these drugs should only be used for acute upper and lower respiratory tract infections in the context of a randomised controlled trial.
We found that calcium channel blockers (CCB) reduced the risk of graft loss by about 25% in randomised studies, compared to placebo or no treatment. CCB also improved the function of grafts, as measured by glomerular filtration rate (GFR) with GFR 4.5 mL/min higher on average in patients receiving CCB compared to placebo. There were fewer studies comparing angiotensin converting enzyme inhibitors (ACEi) to placebo and their results were inconclusive. In studies that compared ACEi to CCB, ACEi worsened GFR by about 11.5 mL/min on average. ACEi also lowered haemoglobin and increased the risk of elevated blood potassium compared to CCB. There were not enough studies of other classes of drugs to draw conclusions about their relative effects. On current evidence CCB might therefore be the best agents for kidney transplant patients.
In November 2015, we searched for clinical trials where hydromorphone was used to treat neuropathic pain in adults. We found one small study that did this and met our requirements for the review. The study had a complicated design. Only a minority of participants had neuropathic pain, with only 94 in the comparison with placebo. Important pain outcomes were not reported. The study provided no convincing evidence of any benefit for hydromorphone over placebo. Of those people who started taking hydromorphone, one in eight stopped because of side effects in the first part of the study. The most common side effects were constipation and nausea, which are typically experienced with opioids. We rated the quality of the evidence as very low because of the study design, poor reporting of important outcomes, and small numbers of participants. Very low quality evidence means that we are very uncertain about the results.
We reviewed 20 studies on the effects of fluoridated water on tooth decay and 135 studies on dental fluorosis. The evidence is up to date at 19 February 2015. Nineteen studies assessed the effects of starting a water fluoridation scheme. They compared tooth decay in two communities around the time fluoridation started in one of them. After several years, a second survey was done to see what difference it made. Around 70% of these studies were conducted before 1975. Other, more recent studies comparing fluoridated and non-fluoridated communities have been conducted. We excluded them from our review because they did not carry out initial surveys of tooth decay levels around the time fluoridation started so were unable to evaluate changes in those levels since then. We reviewed one study that compared tooth decay in two fluoridated areas before fluoridation was stopped in one area. Again, after several years, a second survey was done to see what difference it made. Around 73% of dental fluorosis studies were conducted in places with naturally occurring – not added – fluoride in their water. Some had levels of up to 5 parts per million (ppm). Our review found that water fluoridation is effective at reducing levels of tooth decay among children. The introduction of water fluoridation resulted in children having 35% fewer decayed, missing and filled baby teeth and 26% fewer decayed, missing and filled permanent teeth. We also found that fluoridation led to a 15% increase in children with no decay in their baby teeth and a 14% increase in children with no decay in their permanent teeth. These results are based predominantly on old studies and may not be applicable today. Within the ‘before and after’ studies we were looking for, we did not find any on the benefits of fluoridated water for adults. We found insufficient information about the effects of stopping water fluoridation. We found insufficient information to determine whether fluoridation reduces differences in tooth decay levels between children from poorer and more affluent backgrounds. Overall, the results of the studies reviewed suggest that, where the fluoride level in water is 0.7 ppm, there is a chance of around 12% of people having dental fluorosis that may cause concern about how their teeth look. We assessed each study for the quality of the methods used and how thoroughly the results were reported. We had concerns about the methods used, or the reporting of the results, in the vast majority (97%) of the studies. For example, many did not take full account of all the factors that could affect children’s risk of tooth decay or dental fluorosis. There was also substantial variation between the results of the studies, many of which took place before the introduction of fluoride toothpaste. This makes it difficult to be confident of the size of the effects of water fluoridation on tooth decay or the numbers of people likely to have dental fluorosis at different levels of fluoride in the water.
This review of existing studies was carried out by Cochrane Oral Health authors and the evidence is current up to 3 May 2017. We searched scientific databases for randomised controlled trials (studies where people are randomly put into one of two or more treatment groups) comparing different types of materials for prosthodontic treatment in people who were followed up for at least one year. Of the nine included trials three were conducted in Germany, one in Sweden, one in Spain, one in Switzerland and the USA, one in Denmark, one in Italy, and one in Switzerland. All the included trials were single-centre conducted at university dental clinics and had a parallel-group study design. All the included trials received support from industry. The review included nine studies with 448 participants in which a total of 224 crowns and 132 bridges on natural teeth, and a total of 74 crowns and 25 bridges on implants were used. Each trial was addressing a different type of intervention. The studies had durations up to 10 years but included very small numbers of participants and were assessed as at unclear or high risk of bias. Based on these studies, there is currently insufficient reliable evidence to support which of these materials are more effective. Two trials were at unclear risk of bias and seven were at high risk of bias. The overall quality of evidence was very low, therefore caution should be exercised when generalising the results of the included trials. Future research should aim to provide more reliable information which can help clinicians to decide on appropriate materials for fixed prosthodontic treatment whilst taking into consideration the individual circumstances and preferences of their patients.
Seventeen randomised controlled trials compared deferiprone with desferrioxamine. They report little data on death or end organ damage, so we report the effects of therapy using mainly other markers. Removing excess iron was assessed by iron concentration in the blood and liver; heart function; and the amount of iron passed in urine. However, the amount of iron removed with either deferiprone or desferrioxamine was not consistent; one reason being that outcomes were measured differently. This makes it difficult to compare results between trials. Adverse events included joint pain, nausea, stomach upsets and low white blood cell count with deferiprone and pain or skin reactions at the injection site and joint pain with desferrioxamine. In one trial, the risk of an adverse event with deferiprone was twice that of the risk with desferrioxamine. Two further trials showed a three-fold increased risk of an adverse event with combined deferiprone and desferrioxamine therapy compared with desferrioxamine alone. We found no evidence to change current recommendations to treat iron overload in thalassaemia with deferiprone when desferrioxamine cannot be used or is inadequate. Intensified desferrioxamine treatment or use of other oral iron chelators (or both of these) remains the established treatment to reverse heart problems due to iron overload. Indeed, the US Food and Drug Administration (FDA) recently gave support for deferiprone only to be used as a last resort treatment in patients with thalassaemia, myelodysplasia and sickle cell disease. The danger of raised liver enzymes or a very low white blood cell count with deferiprone means that this treatment should not be used unless close monitoring of full blood counts and liver function is possible. Large trials of chelation therapy with standardised measures of iron stores and end organ damage are needed so valuable trial data can be compared and analysed.
We included 14 studies in this review, involving a total of 6641 participants. All studies lasted between two and 78 weeks. All people included in these studies had received a diagnosis of asthma. Trials included both men and women, and one study included children and young people. All studies looked at VI and FF versus another medication or placebo. In all studies, the VI/FF combination was taken through a dry powder inhaler. We found that participants who received a combination of FF and VI therapy had improved lung function compared with those given placebo, but evidence was insufficient to permit any other conclusions because researchers attempted to answer too many different questions. Evidence was lacking on whether the combination of VI and FF therapy once-daily is better or worse than a twice-daily alternative. More studies are needed, so that we can gain a better understanding of the evidence overall. Overall, the evidence presented in this review is taken from well-designed studies at low risk of bias in terms of decisions on who received which treatment, blinding and how to report outcomes for participants who did not finish the study. However, because we were not able to combine results for many of our outcomes of interest, or because the outcome was rare, we judged the quality of the evidence overall to be low to moderate.
Authors fromCochrane Oral Healthcarried out this review and the evidence is current up to 15 August 2018. It includes 96 studies published between 1955 and 2014: seven studies with 11,356 randomised participants reported the effects of fluoride toothpaste up to 1500 ppm on the primary teeth; one study with 2500 randomised participants reported the effects of 1450 ppm toothpaste on the primary and permanent dentition; 85 studies with 48,804 randomised participants reported the effects of toothpaste up to 2400 ppm on the permanent teeth of children up to 18 years of age; and three studies with 2675 randomised participants reported the effects of up to 1100 ppm toothpaste on the permanent teeth of adults. Most studies assessed decay after participants had been using the toothpastes for 36 months. We present below findings for which there is moderate- or high-certainty evidence. In primary teeth of young children, brushing teeth with a toothpaste containing 1500 ppm fluoride reduced the amount of new decay when compared with non-fluoride toothpaste; the amount of new decay was similar with 1055 ppm compared with 550 ppm fluoride toothpaste; and there was a slight reduction in the amount of new decay with 1450 ppm toothpaste compared with 440 ppm fluoride toothpaste. Eighty-one studies assessed the effects of different strengths of fluoride toothpaste compared against each other (seven different strengths in 21 combinations) in permanent teeth of children and adolescents. We found that there was less new decay when toothbrushing with toothpaste containing 1000 to 1250 ppm or 1450 to 1500 ppm fluoride compared with non-fluoride toothpaste, and that toothbrushing with 1450 to 1500 ppm fluoride toothpaste reduced the amount of new decay more than 1000 to 1250 ppm toothpaste. We found that there was a similar amount of new decay when children and adolescents used a toothpaste of 1700 to 2200 ppm or 2400 to 2800 ppm fluoride compared to 1450 to 1500 ppm toothpaste. The evidence for the effects of other strengths of toothpaste was less certain. In permanent teeth of adults of all ages, 1000 or 1100 ppm toothpaste reduced decay compared with non-fluoride toothpaste. Most studies did not measure harmful effects of toothpaste use, but when reported, effects such as soft tissue damage and tooth staining were minimal. There is high-certainty evidence that toothpaste containing 1000 to 1250 ppm fluoride is more effective than non-fluoride toothpaste. There is moderate-certainty evidence for the other findings reported in 'Main results' above. For other toothpaste strengths compared against each other or against non-fluoride toothpaste, there are too few studies with too few participants to have any clarity about the effects. There are benefits of using fluoride toothpaste at certain strengths to prevent tooth decay when compared with non-fluoride toothpaste. The stronger the fluoride concentration, the more decay is prevented. For many of the comparisons of different strengths of toothpaste, the findings are uncertain and could be challenged by further research. The choice of fluoride toothpaste for young children should be balanced against the risk of fluorosis.
The evidence is current to October 2013. We included studies in children (age > 28 days and < 18 years) and adult patients (age > 18 years) of either gender who received mannitol or hypertonic saline during craniotomy for brain tumour. We reran the search in January 2017 and found five potential studies of interest which have been added to a list of ‘Studies Awaiting Classification' and will be incorporated into the formal review findings during the review update. We found six studies with 527 participants. Three studies reported the level of brain relaxation. Hypertonic saline may provide better brain relaxation than mannitol. The length of intensive care unit stay and hospital stay was reported by one study. No study reported on the effects of mannitol and hypertonic saline on mortality, the condition of the patient three months after the operation or patient quality of life. Based on our results, we would expect that of 100 patients who received hypertonic saline during surgery, around 22 patients would fail to have adequate brain relaxation compared with 36 patients given mannitol. The quality of evidence for brain relaxation with use of hypertonic saline is low. Further research is needed to assess more important issues such as long-term mortality, long-term outcomes, adverse events and quality of life with use of the two fluids.
We found 25 randomised clinical trials (studies where participants with ADHD were randomly assigned to one of two or more groups) involving a total of 2690 participants. The trials lasted between five weeks and two years. The social skills training generally focused on teaching the children how to 'read' the subtle cues in social interaction, such as learning to wait for their turn, knowing when to shift topics during a conversation, and being able to recognise the emotional expressions of others. Social skills training often consists of role play, exercises and games, as well as homework. Children in the control groups either received no intervention or were placed on a waiting list. We found no significant differences between social skills training versus controls on social skills, emotional competencies, and general behaviour as assessed by teachers. Compared with the children who had no social skills training, teachers rated those who had been in the social skills groups as having fewer ADHD symptoms at the end of treatment.. However, this finding was questionable because our other analyses did not support it. We found no indications of harmful effects. All trials suffered from methodological problems such as overestimation of benefits and underestimation of harms. Many studies were also difficult to compare because they involved different interventions. The results from some trials were not very precise, which means it is difficult to be confident in the results. In seven trials, study authors were board members of pharmaceutical companies, had received funding from such companies, or had performed previous research on the topic. We are unable to conclude whether social skills training is beneficial or not for children with ADHD. We need more randomised clinical trials on social skills training for children and adolescents with ADHD that have a sufficient number of participants and higher methodological quality.The evidence base regarding adolescents is especially weak. We found no adverse treatment effects.
When comparing cephalosporins against penicillins, we found 27 studies, involving 7299 women as of September 2014. The quality of the studies was generally unclear and three studies reported drug company funding. Cephalosporins and penicillins had similar effects in reducing infections after caesareans and similar adverse effects. However, none of the studies considered infections after the women left hospital. None of the studies looked at outcomes on the babies. Other evidence show tetracyclines can cause discolouration of teeth in children and are best avoided. Consideration also needs to be given to antibiotics compatible with breastfeeding. We were unable to assess bacterial resistance, and this is crucial when considering which antibiotic might be used. At caesarean sections, cephalosporins and penicillins have similar benefits and side effects for mothers when considering infections immediately following the operation but there is no information on babies. Clinicians need to consider bacterial resistance and women's individual circumstances.
We included 14 trials (854 participants with leprosy). Participants mostly had only one wound on one foot. Wounds were mainly simple (not infected) and varied in size and depth, and were less than one year old; some wounds were more complicated. Participants ranged from 18 to 74 years old. In the 11 studies which reported gender, more men were included. Studies were conducted in Brazil, Ethiopia, Egypt, Indonesia, Mexico, South Korea, and India, in mainly outpatient clinics. Most studies did not report funding sources. Treatments were mostly compared to dry dressings or dressings soaked in differing solutions. Other comparisons included special plaster, canvas shoes, and foot soak. Treatments evaluated included: laser therapy, light-emitting diode (LED), zinc tape or paste, pentoxifylline injections, exposure to pulsed magnetic fields, wax therapy, ketanserin gel, amniotic membrane gel, phenytoin powder, plaster shoes, and footwear. Outcomes were measured from the beginning of treatment. The following key results are based on very low-certainty evidence, so we are not sure of these results. Three studies compared zinc tape with other interventions: magnesium sulphate glycerin, povidone iodine, or gauze soaked in Eusol. After one month of treatment, the number of healed ulcers was higher and the ulcer area was lower in the zinc tape group compared with magnesium sulphate glycerin. There was no clear difference in the reduction of ulcer area at six weeks when comparing zinc tape to povidone iodine. The healing time for deep ulcers in the zinc tape group was 17 days compared to 30 days with gauze soaked in Eusol. This study also reported no signs of skin sensitisation in either group at two months; the other two studies provided no data on adverse events. Two studies compared topical phenytoin to salt water dressing. One study showed a greater reduction in ulcer area with phenytoin. The other study found a greater reduction in ulcer volume in favour of phenytoin. Both studies measured this outcome after four weeks of treatment. No adverse events were observed in either study. The five studies just described did not assess prevention of ulcers, as the therapies were for treatment rather than prevention. Two studies compared protective footwear (with or without self-care) with either polyvinyl chloride (PVC - a form of plastic) boots, or pulsed magnetic fields plus self-care and protective footwear. In the study comparing canvas shoes versus PVC boots, none of the participants who had scars at the start developed new ulcers over one year. There was no clear difference between the groups in the number of people whose ulcers had healed. In the study assessing pulsed magnetic fields, prevention of new ulcers was not measured; however, there was no clear difference between groups in volume of ulcers four to five weeks after the start of treatment. Only one study reported information about adverse events: the PVC boots could become very hot in strong sunlight, with the possibility of burning. We judged the evidence as very low certainty, meaning the results are ambiguous. There were concerns regarding how participants were allocated to treatments, whether participants and study investigators knew which treatment had been received, and the number of participants who dropped out of the studies.
We found no completed studies that compared keyhole surgery and radiotherapy alone or combined with chemotherapy. Two ongoing trials did fulfil our selection criteria, however neither are yet complete. One has an estimated completion date of June 2021 and the other planned to start recruiting patients mid-2016. There are not yet any completed studies to include in the review so there are no results. The role of keyhole surgery in the management of throat cancer is expanding as is demonstrated by its incorporation into the current national guidelines in the USA. Evidence is mounting regarding its outcomes both in terms of survival and fewer side effects. Based on this review, there is currently no high-quality evidence from randomised controlled trials that compare keyhole surgery with radiotherapy and chemotherapy for patients with throat cancer.
The review included 26 trials with a total of 2051 participants. The findings suggested that music listening may have a beneficial effect on preoperative anxiety. Most trials presented some methodological weakness. Therefore, these results need to be interpreted with caution. However, these findings are consistent with the findings of three other Cochrane systematic reviews on the use of music interventions for anxiety reduction in medical patients. Therefore, we conclude that music interventions may provide a viable alternative to sedatives and anti-anxiety drugs for reducing preoperative anxiety.
The findings are based on eight studies measuring a variety of outcomes, using a range of standardised measures. It was possible to combine results (meta-analysis) for nine comparisons. Results from four of these meta-analyses suggest that parenting programmes may be effective in improving parent responsiveness to the child, and parent-child interaction, both post-intervention and at follow-up. Infant responsiveness to the mother also showed improvement at follow-up. The results of the other five meta-analyses we carried out were inconclusive. Further rigorous research is needed that provides both short- and long-term follow-up of the children of teenage parents, and that assesses the benefits of parenting programmes for young fathers as well as young mothers.
We included three randomized controlled trials with a total of 140 participants. All three studies included participants with risky alcohol intake (3 to 40 AU daily) who were in need of surgery. These studies investigated intensive alcohol interventions aimed at complete alcohol cessation at the time of surgery compared with no intervention. Interventions included educational strategies for alcohol withdrawal and relapse prevention. Programmes were started three months before surgery, four weeks before surgery, and from the time of admission to surgery, and continued for six weeks after surgery, respectively. The quality of the evidence is of moderate to low quality. In all three studies, intensive intervention programmes clearly increased the number of participants who quit drinking alcohol. The occurrence of postoperative complications appeared to be reduced as well. Of 61 participants in the intervention groups, 20 had complications requiring treatment, compared with 33 of 61 participants in the control groups (moderate-quality evidence). Of 70 participants in the intervention groups, 41 successfully quit drinking, compared to five of 70 participants in the control groups (moderate-quality evidence). Data were insufficient to show the effect of quitting drinking on the number of deaths (low-quality evidence), and results show no effect on length of hospital stay. None of the included studies reported on the number of participants who continued to avoid risky drinking in the longer term (at three-, six-, nine-, and 12-month follow-up). Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could be more motivated and/or more interested in participating in clinical research or otherwise different, and effects may therefore have been overestimated for both intervention and control groups in these studies. More research is needed and new strategies are required to improve outcomes after surgery among risky drinkers.
We found five studies including more than 100 schools that compared an asthma education programme for school staff against a control. Researchers measured outcomes for teachers and staff, and often for children or parents as well, most often at between 1 and 12 months. We conducted the most recent search for studies on 29 November 2016. We could not tell whether educating school staff reduced the number of children who needed to visit the emergency department (ED) or hospital, and no studies reported any deaths. Study authors measured asthma control in different ways but found little benefit, especially more than a year after the intervention was provided. Schools that received asthma education stuck to asthma policies better and staff were better prepared; more schools that had received staff asthma training had written asthma policies compared with control schools, more intervention schools showed improvement in measures taken to prevent or manage exercise-induced asthma attacks and more staff at intervention schools felt that they were able to administer salbutamol using a spacer. We wanted to assess what the education sessions should cover and how they could best be delivered, but we did not find enough information to do this. To sum up, asthma education for school staff increases asthma knowledge and preparedness in the schools, but we do not know much about actual benefits of this education for children with asthma. The small number of studies and the variation between them mean that we cannot be sure of the overall effect of educating school staff about asthma. The ways researchers allocated schools, teachers or children to groups may have caused some bias. Also, the fact that teachers knew whether they were in the active or control group may have affected how they behaved and answered questionnaires, and this may have led to overestimation of benefits. Lots of people who were included in the studies did not return questionnaires at the end of the study, which means that we do not have a full picture of the results of asthma education interventions.
Most of the evidence on non-drug interventions was based on just one or two studies and so the findings are not definitive.  However, we found that immersion in water, relaxation, acupuncture and massage all gave pain relief and better satisfaction with pain relief. Immersion and relaxation also gave better satisfaction with childbirth. Both relaxation and acupuncture decreased the use of forceps and ventouse, with acupuncture also decreasing the number of caesarean sections. There was insufficient evidence to make a judgement on whether or not hypnosis, biofeedback, sterile water injection, aromatherapy, and TENS are effective for pain relief in labour. Overall, there were more studies of drug interventions. Inhaled nitrous oxide and oxygen (Entonox®) relieved pain, but some women felt drowsy, nauseous or were sick.  Non-opioid drugs (e.g. sedatives) relieved pain and some gave greater satisfaction with pain relief than placebo or no treatment, but satisfaction with pain relief was less than with opioids. Epidurals relieved pain, but increased the numbers of births needing forceps or ventouse, and the risk of low blood pressure, motor blocks (hindering leg movement), fever and urine retention. Combined spinal-epidurals gave faster pain relief but more women had itching than with epidurals alone, although urinary retention was less likely to be a problem. Local anaesthetic nerve blocks gave satisfaction but caused side effects of giddiness, sweating, tingling, and more babies had low heart rates. Parenteral opioids (injections of pethidine and related drugs) are less effective than epidural but there was insufficient evidence to make a judgement on whether or not they are more effective than other interventions for pain relief in labour. Overall, women should feel free to choose whatever pain management they feel would help them most during labour. Women who choose non-drug pain management should feel free, if needed, to move onto a drug intervention. During pregnancy, women should be told about the benefits and potential adverse effects on themselves and their babies of the different methods of pain control. Individual studies showed considerable variation in how outcomes such as pain intensity were measured and some important outcomes were rarely or never included (for example, sense of control in labour, breastfeeding, mother and baby interaction, costs and infant outcomes). Further research is needed on the non-drug interventions for pain management in labour.
We searched scientific databases to find all studies on treatments for PPS up to July 2014. We found 13 studies involving a total of 675 participants that were of sufficient quality to include in this review. Ten studies evaluated the effects of drugs (modafinil, intravenous immunoglobulin (IVIg), pyridostigmine, lamotrigine, amantadine, prednisone), and three studies evaluated other treatments (muscle strengthening, rehabilitation in a warm climate (that is temperature ± 25°C, dry and sunny) and a cold climate (that is temperature ± 0°C, rainy or snowy), static magnetic fields). IVIg is a treatment in which antibodies that have been purified from donated blood are given as an infusion into a vein over a period of time. There was moderate- and low-quality evidence that IVIg has no beneficial effect on activity limitations in the short term and long term, respectively. Evidence for effectiveness on muscle strength was inconsistent, as results differed across studies. IVIg caused minor side effects in a substantial proportion of the participants. Lamotrigine is a drug used to help control certain kinds of epilepsy and to treat bipolar psychiatric disorder. Results of one trial provided very low-quality evidence that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations, and in this study it was well-tolerated. We based these conclusions on results of only one small trial with important limitations in study design. There was very low-quality evidence that muscle strengthening of thumb muscles is safe and beneficial for improving muscle strength. Again, we based these conclusions on results of only one small trial with important limitations in study design, and they are applicable only to thumb muscles. Static magnetic fields is a therapy in which electrical currents are applied to the skin with the intention of reducing pain. There was moderate-quality evidence that static magnetic fields are safe and beneficial for reducing pain directly after treatment, although functional effects on activity limitations and long-term effects are unknown. Finally, there was evidence varying from very low quality to high quality that modafinil, pyridostigmine, amantadine, prednisone and rehabilitation in a warm or cold climate are not beneficial in PPS.
We identified one new trial, so there are now three studies involving 108 participants. All studies were conducted in Brazil during 2004, 2007, and 2012. Two trials evaluated the effects of carvedilol versus placebo; one trial assessed rosuvastatin versus placebo. The results were inconclusive that carvedilol reduced all-cause mortality or improved quality of life more than placebo. The safety profile of carvedilol for Chagas cardiomyopathy remains unclear. One study assessed the effect of rosuvastatin versus placebo, but did not show an effect size. Therefore, the results from available clinical trials neither support nor reject the use of carvedilol or rosuvastatin in treating this clinical entity. Further investigation is warranted to investigate the exact applicability of conventional heart failure treatment agents in Chagas cardiomyopathy. Our confidence in the results of this review is very low because the included trials had a high risk of bias and were small. which generated imprecise results. 15 February 2016.
This review attempted to evaluate this assumption. We found only one published study from developing countries and none from developed countries. The only study included in the review showed an increase in VCT uptake after home-based VCT intervention. Because of the limited evidence to date, however, further research is needed to evaluate if home-based VCT is better than facility-based VCT or other testing methods.
We found 12 studies, eight weeks in duration, that randomly assigned 7439 adult people with uncomplicated mild-to-moderate hypertension to aliskiren at doses ranging from 75 mg to 600 mg or placebo. All studies were funded by the manufacturer Novartis. Detailed information regarding adverse events, obtained from nine clinical study reports submitted to regulators, are included in this update. We concluded that aliskiren is better than placebo at lowering blood pressure and that the magnitude of this effect could be similar to other classes of drugs when 300 mg, which is the maximum recommended dose, is used. Aliskiren 300 mg reduced blood pressure by eight points in the upper number (called systolic blood pressure) and five points in the lower number (called diastolic blood pressure). Aliskiren had no effect on blood pressure changeability. Due to very limited information regarding change in heart rate and pulse pressure (difference between upper and lower number) it was not possible to analyze these outcomes. The studies were too short in duration to assess side effects. Aliskiren did not increase death, non-fatal serious adverse events or withdrawal due to side effects. The most common adverse events observed were headache, diarrhoea, dizziness and fatigue. Diarrhoea was considerably increased with aliskiren 600 mg as compared to placebo. The decrease in blood pressure at the recommended dose was rated as moderate-quality evidence and adverse event data was graded as low-quality evidence as included studies were assessed to have high likelihood of reporting and funding bias.
Five trials with 246 participants were included. There is no evidence that antidepressants have a beneficial effect on narcolepsy. Moreover, despite the clinical consensus recommending their use for cataplexy, there is scarce evidence to support the use of antidepressant drugs to treat this symptom.
The review authors identified only two small randomised controlled trials with a combined total of 57 participants testing the safety and effectiveness of this treatment. The findings were inconsistent. In one trial, pain at rest, pain-free walking distance, ankle brachial blood pressure index, and the number of amputations all clearly improved in the group receiving mononuclear cell implantation. In the other trial only the number of amputations showed a significant improvement in the treatment group compared with the control group. No deaths were reported during the study period. Quality of the evidence The two included studies differed from each other in how they obtained the cells for injection and assessed the clinical effects at different time points, up to three months in one trial, and six months in the other. They were classified as having a moderate risk of bias with unclear issues regarding their methods and the overall quality of the evidence was considered moderate.
The quality of the included studies was difficult to grade due to a lack of information. These are not, therefore, high quality studies. We found a small amount of evidence that reducing uric acid levels may slow down damage to kidneys but no evidence that it improves blood pressure or any of the other cardiovascular markers that were investigated. The number of patients requiring dialysis treatment for complete kidney failure appears unchanged. Two measures of kidney failure (serum creatinine and glomerular filtration rate) were improved at six and 12 months but not at two years. The amount of protein in the urine was also reduced by treatment. We found no clear effect on death, blood pressure, rates of hospitalisation, or side effects of treatment. There is limited data which suggests urate lowering therapy may slow down damage to the kidneys but the conclusion is very uncertain. Benefits were not observed at all time points and study quality was generally low. Larger studies are required to study the effect of uric acid lowering therapy on CKD progression.
The review, however, looks at only eight studies. The methods of most of these studies were considered poor and there was no definitive description of crisis intervention or crisis care for studies included before 2006, meaning there was a lack of focus on crisis care in its pure form. Most studies excluded service users with alcohol or drug misuse, and those who were a danger of being harmful to themselves or others. The authors of the review suggest more studies are needed to create a stronger evidence base. Crisis care may be currently delivered without sound and good quality evidence. For example, no data or information were available on carer input, concordance or the willingness of service users to take medication and the number of relapses experienced by service users. Finally, despite reports of staff 'burn-out', staff satisfaction with crisis care was not assessed. This plain language summary has been prepared by Ben Gray, Senior Peer Researcher, McPin Foundation (. http://mcpin.org/).
For some medicines there were no published trials. For other medicines there was inadequate information. For some medicines, there was adequate information, but the results could be overturned by just a few unpublished studies in which there was no effect. None of these could be regarded as reliable. There remained 53 pairs of medicine and dose with reliable evidence. The range of results with single dose analgesics in participants with moderate or severe acute pain was from 7 out of 10 (70%) achieving good pain relief with the best medicine to about 3 out of 10 (30%) with the worst medicine. No medicine produced high levels of pain relief in all participants. The period over which pain was relieved also varied, from about two hours to about 20 hours. Good results were found for medicines combined in a fixed dose in a single tablet, or medicines made for rapid absorption from the stomach. Commonly used analgesic medicines at the recommended or licensed doses produce good pain relief in many, but not all, people with acute pain. The reasons for this are varied, but people in pain should not be surprised if medicines they are given do not work for them. Alternative analgesic medicines or methods should be found that do work.
We found eight studies on 570 people with cough lasting over three weeks. Studies included different types of participants in terms of age, duration of coughing and risk factors for cough. Studies also varied in types of ICS, doses, treatment lengths and types of inhaler used. Cough severity was measured using different scales. We looked at the proportion of people who were clinically cured or showed a significant improvement in cough severity as our primary outcome, but the data were too mixed to be able draw any conclusions. These differences between studies also prevented meaningful pooling of study results for proportion of people showing improvement in cough and average improvement in one specific type of cough scale. There was low quality evidence that ICS reduced cough severity score. There was not enough data about changes in pulmonary function, complications of cough and markers of inflammation to allow pooling of results.There was evidence of moderate quality that ICS treatment did not increase the risk of adverse events. This review has shown that the effects of ICS for subacute and chronic cough are inconsistent. Further studies with more consistent patient populations, interventions, outcome measures and reporting are needed to determine whether ICS help subacute and chronic cough in adults. This Cochrane plain language summary was written in December 2012.
We are moderately certain that CBT, exercise, and relaxation techniques probably decrease symptoms of depression for patients treated with long-term dialysis. Counselling may slightly decrease depression symptoms, while we are uncertain whether acupressure, telephone support, or meditation make any difference. We found moderate certainty evidence that CBT provides higher quality of life for dialysis patients. Studies did not measure effects of psychosocial treatments on major depression, suicide risk, and whether therapies made any difference to anxiety, hospital admissions, or withdrawal from dialysis treated is uncertain. Adverse events from treatment is very uncertain. Some study authors did not report the methods for their studies clearly, so we could not be certain whether patients truly had a random chance of being in each treatment group or whether the trial results were assessed by people knowing which treatments that patients actually received. For most outcomes, we identified very few studies, which decreased our confidence in the results. CBT, exercise, and relaxation techniques probably decrease depressive symptoms for dialysis patients while CBT also improves life quality. Counselling may slightly reduce depression among those receiving dialysis. We are not certain whether interventions prevent or treat major depression, anxiety, suicide risk, or withdrawal from dialysis care before death or whether psychological and social treatments have adverse effects.
The five randomised trials included in the review involved only 428 elderly patients. One small and potentially biased trial of 23 patients with undisplaced intracapsular fracture provided limited evidence that surgical fixation increased the chances of the fracture healing. The four trials on extracapsular fractures tested a variety of surgical techniques and implant devices and only one trial involving 106 patients can be considered to test current practice. This trial found no major difference between surgery and traction for people with extracapsular fractures. However, people who had surgery had better anatomical outcomes, tended to leave hospital sooner, and seemed less likely to lose their independence. The review concluded that overall there was insufficient evidence to determine if surgery is better than bed rest and traction for the two categories of hip fractures tested in randomised trials. However, nowadays most people with hip fracture are treated surgically where it is safe to do so. This reflects advances in surgery and anaesthesia and a clearer understanding of the benefits of early mobilisation and of the risks of prolonged hospital stay.
There was reasonable randomised controlled trial (RCT) evidence in L. braziliensis infections that oral pentoxifylline plus IVSSG was better than IVSSG alone; IVMA was better than IM aminosidine sulphate and IV pentamidine isethionate; and IMMA was better than the Bacillus Calmette-Guérin vaccine. Regarding L. panamensis infections, oral ketoconazole for 28 days and oral miltefosine and topical PR-MBCL were all better than placebo; oral allopurinol better than IVMA, aminosidine sulphate 12mg/kg/day and 18mg/kg/day for 14 days were better than aminosidine sulphate 12mg/kg/day for 7 days. There was complete absence of RCT evidence on alternative treatments, surgery, oral itraconazole and fluconazole, oral antibiotics like rifampicin, metronidazole and cotrimoxazole, intravenous or topical amphotericin B, oral dapsone, photodynamic therapy, promoting healing therapies, laser, and cryotherapy treatments. Moreover, none of the studies reported quality of life, "microbiological or histopathological cure of skin lesions", changes in ability to detect the parasite by diagnostic methods (e.g. smear or culture) or mortality. No general consensus on optimal treatment has been achieved but alternatives to intramuscular or intravenous treatments are under active investigation. The evidence base for the treatment of American cutaneous and mucocutaneous leishmaniasis has many limitations due to poor design and reporting of clinical trials. Because resources are limited for clinical research into neglected diseases, there is a need for prioritising properly designed clinical trials. Therefore, we suggest the creation of an international strategy to improve the quality and standardization of future trials for a better evidence-based strategic approach in the future.
Twenty-five studies, involving 6382 people, were included in this review. These studies lasted between eight and 60 weeks. All of the people included in the studies had asthma, of different severity. Both men and women were included, and some of the studies included children and young people. All studies compared omalizumab versus placebo. In keeping with current medical practice, most studies (21 of 25) used omalizumab given by injection under the skin. Some of the older studies used omalizumab injected into a vein or given by inhalation. The evidence presented here is current to June 2013. Most of the studies were sponsored by the pharmaceutical industry. We found that people receiving omalizumab were less likely to have a flare-up (‘exacerbation’) of their asthma. For example, on average, 26 of 100 people who were receiving placebo (over a 16 to 60-week period) had an exacerbation compared with an average of 16 of 100 people receiving omalizumab. People receiving omalizumab were also more likely to be able to reduce the doses of inhaled steroids. For example, on average, 21 of 100 people with moderate or severe asthma who were receiving placebo were able to completely stop their inhaled steroids (over a 28 to 32-week period) compared with an average of 40 of 100 receiving omalizumab. People receiving omalizumab also experienced improvement in their asthma symptoms and in their health-related quality of life. People receiving omalizumab were no more or less likely to have unwanted side effects overall. However, people receiving omalizumab were more likely to have skin reactions at the site of the injection. Perhaps unfortunately, many of the trials in this review included participants with moderate asthma, and this drug is not licenced for this group. More trials need to focus on whether this drug is effective in people with the most severe asthma; evidence for efficacy in this group is poor, in spite of current guidelines. The evidence presented in this review is generally of moderate quality. Most of the studies did not clearly explain how investigators decided which people would receive omalizumab and which would receive placebo, and this decision is an important part of well-conducted studies.
The evidence on which this review is based is up to date as of 28 February 2013. Twelve studies with a combined total of 689 participants were included in this review. Participants ranged in age from 16 to 68 years and most participants (90%) were male. All of the studies compared different types of surgical treatments, and each study evaluated a different aspect of surgical treatment such as different types of plates, screws, or wires or how long the jaw was immobilized after surgery. There were concerns about the design and quality of all the studies. All the studies evaluated different aspects of surgical treatment. None of the studies evaluated non-surgical treatments such as intermaxillary fixation and no study compared surgical treatment with non-surgical treatment. As a result there is no clear evidence to indicate which approach is the best to manage these fractures. The quality of the evidence found is poor. Recommendations are made for further well-conducted research studies in this area to be undertaken.
Disulfiram showed a trend toward fewer dropouts from psychosocial treatment when compared to placebo (three trials) or naltrexone (three trials) but this was not statistically significant. Assessing cocaine use, single studies were in favour of disulfiram on number of weeks of abstinence in one out of four comparisons when compared with placebo and on maximum weeks of consecutive abstinence and number of people achieving three or more weeks of consecutive abstinence in one study comparing disulfiram to no pharmacological treatment.   The included studies did not specifically investigate the adverse effects of disulfiram itself or its potential to increase alcohol and cocaine adverse effects.
We included three randomised controlled trials in which a total of 77 women took part. Two studies compared metformin versus megestrol acetate (a form of progesterone), and one study compared metformin plus megestrol acetate versus megestrol acetate alone. Women in all studies received treatment for approximately 12 weeks. The evidence is current to 10 January 2017. Comparisons of metformin versus megestrol acetate have provided insufficient evidence to show differences in effectiveness for curing endometrial hyperplasia. It remains uncertain whether there is any difference between metformin and megestrol acetate in reducing hysterectomy rates or abnormal uterine bleeding in women with endometrial hyperplasia. Although both studies provided data on progression of endometrial hyperplasia to endometrial cancer, there were no events in either arm, and study authors reported no data on adverse effects. When metformin plus megestrol acetate is compared with megestrol acetate, differences in effectiveness between groups treating endometrial hyperplasia remain unclear. Three of eight patients in the metformin plus megestrol acetate study arm reported nausea. Occurrence of other adverse events is unclear. We rated the quality of evidence as very low for all outcomes owing to very serious risk of bias (associated with poor reporting, attrition, and limitations in study design) and imprecision.
We found seven relevant studies of 1550 people with COPD. We did not include studies that gave other treatments, such as an exercise programme or longer educational sessions, along with an action plan. People in three studies had ongoing support to help them use the action plan. People in the included studies had moderate to severe symptoms and were followed up for six or 12 months. Key results People with COPD who are given an action plan have fewer emergency department visits and hospital stays related to breathing problems over a year. We calculated that for every 19 people given an action plan, one person would avoid a hospital stay for an exacerbation. People with an action plan took more corticosteroid and antibiotic medicines for exacerbations - on average just under one more course of corticosteroids and two more courses of antibiotics over a year. Some studies showed that giving people an action plan improved their ability to recognise and self-start treatment for worsening COPD symptoms. Giving people an action plan made no difference in their chance of dying from any cause over a year, but this finding showed some variability. We could not say whether follow-up phone calls added benefit over following an action plan alone. Quality of the evidence The evidence in this review is generally independent and reliable, and we are very or moderately certain about the results. Conclusions We believe that people with COPD should be given an individualised action plan with a short educational component so they can benefit from fewer and shorter hospital stays, better understanding of the need to self-start treatment and appropriate use of medication for exacerbations.
We found 12 completed trials (involving 1871 infants). Most trials, particularly those trials conducted more recently, used reliable methods. Evidence is up to date as of 3 May 2019. The combined analysis of data from these trials shows that feeding with formula increases rates of growth during the hospital stay, but is associated with a higher risk of developing the severe gut disorder called 'necrotising enterocolitis'. There is no evidence of an effect on survival or longer-term growth and development. The currently available evidence suggests that feeding preterm infants with artificial formula (rather than donor breast milk when mother's own breast milk is not available) is associated with faster rates of growth, but with a near-doubling of the risk of developing necrotising enterocolitis. Further, larger trials could provide stronger and more precise evidence to help clinicians and families make informed choices about this issue. Currently, four such trials (involving more than 1100 infants) are ongoing internationally, and we plan to include the data from these trials in this review when these become available.
The two randomised controlled trials included in this review tested arthroplasty versus internal fixation in a total of 148 mainly female and older participants. Both trials had methodological flaws that may affect the validity of their results and there was a general lack of evidence on long-term effects. One of the trials found a longer length of surgery for the arthroplasty and both trials found an increased need for blood transfusion for the arthroplasty. Pooled data from the two trials showed no statistically significant differences between the two procedures for reoperations, wound healing complications or mortality at one year. Neither trial found a significant difference in longer-term function. Overall, the evidence from the two small trials comparing these two approaches for treating extracapsular hip fractures was too limited to make any definite conclusions as to which is better.
Randomised controlled trials of preterm babies below 32 weeks' gestation or below 1500 grams at birth who were treated with CPAP applied within the first 15 minutes of life compared with babies who were given either (1) routine supportive care such as oxygen therapy or (2) mechanical ventilation. There were a total of seven studies involving 3123 infants. They were generally of moderate quality. Parents and care-givers would have known which treatment group the babies were in, but we judged this not to be important for most outcomes measured. In the four studies (765 babies) comparing CPAP with supportive care, CPAP resulted in fewer infants requiring further breathing assistance but there was considerable inconsistency between the studies. In the three studies (2354 babies) that compared CPAP with assisted ventilation with or without surfactant, CPAP resulted in a small but clinically important reduction in BPD and the combined outcome of BPD and mortality. There was a reduction in the need for mechanical ventilation and the use of surfactant in the CPAP group.
Deep venous incompetence (DVI) is a problem in the veins that can lead to leg ulcers (sores), pain and swelling. It may be caused by a problem in the valves of the vein, by a blockage of the veins or by a combination of these events. For most people, wearing special compression stockings and treating the ulcers is enough. When this does not ease the problem, surgery is sometimes tried. This review includes four studies with a total of 273 participants. All included studies reported on outcomes following surgical repair of venous valves (valvuloplasty). We did not identify studies investigating other surgical procedures for the treatment of patients with DVI. All included studies investigated primary valve incompetence (when valves do not close properly because of laxity of the vein wall or valve cusps). We found no trials that investigated the results of surgery for secondary valvular incompetence (when valves do not close properly, for example, when valves are damaged as a result of deep vein thrombosis) or for the obstructive form of DVI. As different outcomes were reported, it was not possible to combine the results of these studies. The methodological quality of the included studies was low, mainly because information regarding allocation of treatment and blinding was missing, or because data were incomplete or were poorly presented. Ulcer healing and ulcer recurrence were not reported in one study, and the remaining three studies did not include patients with ulcers or active ulceration. Three studies reported no significant complications of surgery or no incidence of DVT during follow-up. One study did not report on the occurrence of complications. Clinical changes were assessed by subjective and objective measurements, as specified in the clinical, aetiological, anatomical, and pathophysiological (CEAP) classification score. This requires vascular laboratory measurements of lower limb haemodynamics before and after surgery. Tests include an overall evaluation of venous function with venous refilling time (VRT) or ambulatory venous pressure (AVP). Results show improvement in clinical symptoms and muscle pumping function and significant improvement in the haemodynamic status of patients who had external valvuloplasty along with surgery to the superficial venous system. In patients who had surgery to the superficial venous system only, clinical symptoms improved, but no improvement in muscle pumping function was reported. Evidence is not sufficient to show the effects of surgery on the treatment of patients with DVI. The individual trials included in this review have demonstrated possible long-term benefit in certain groups of patients, but these trials were small, used different methods of assessment and overall were of poor quality. They did not include patients with severe DVI. Trials investigating the effects of other surgical procedures on the deep veins are needed. Until evidence from such trials becomes available, conventional conservative measures, such as high compression therapy or elasticated hosiery, remain the treatments of choice.
The aim of this review was to determine if homocysteine lowering therapies effectively reduce cardiovascular event rates in kidney transplant recipients. A single study was identified that randomised 4110 adult participants with a functioning kidney transplant to homocysteine lowering with folic acid and high dose multivitamins or to low dose multivitamins and followed them for an average of four years. Despite effectively lowering homocysteine levels, there was no evidence of benefit for any of a range of cardiovascular events. Similarly there was no evidence of harm.
We searched for studies in August 2017. We included eight studies, involving 399 adults with traumatic brain injuries, in this review. Most study participants were men in their mid-thirties who had severe brain injuries. We found no studies that included children. The fitness training programmes were conducted in a range of settings including hospital, community and at home. In six of the eight studies all fitness training sessions were supervised. The type of fitness training varied, and included exercising on a fixed cycling machine, in water, on gym equipment such as a treadmill, home-based exercise, and a fitness group in the military. In six of the eight studies the prescribed intensity, duration and frequency of fitness training met the guidelines set by the American College of Sports Medicine. Three of the eight studies, with 67 participants, assessed change in fitness at the end of the treatment programme. Exercise was conducted on a fixed cycling machine in two studies, and in water in the third, and all sessions were supervised. The fitness training was compared to non-exercise interventions in two of these studies, and to no intervention in the third study. We combined the results of the three studies, which demonstrated an average (mean) improvement of 35 watts on an exercise test in the fitness training groups compared to the non-exercise intervention and no intervention groups. This improvement represents approximately a 36% improvement in fitness from the start of the study, which is a large effect. However, this estimate is uncertain and the difference is likely to be between 3 to 68 watts, which may or may not be important clinically. More than one study reported on six other outcomes; body composition, strength, tiredness, depression, quality of life and walking. It was unclear whether fitness training was better or worse than the non-exercise interventions or no intervention at improving these outcomes. Measures of cognition, activities of daily living, and return to everyday activities were only measured in one study, and there were no studies that measured the effect of fitness training on levels of physical activity and motivation. Only three studies examined the effect of fitness training beyond the end of the programme, but these could not provide a clear answer regarding the long-term effects of fitness training. In the five studies that provided supervision for all fitness training sessions, all participants in the fitness training groups completed the studies. Treatment attendance varied between studies, and was reported as ranging from 59% to 100%, and was not reported for two studies. There was no evidence of harm caused by fitness training in any study. Our certainty in these findings is reduced due to the low quality of the evidence caused by small numbers of study participants, poor reporting of some study details, and possible errors in the way some of the studies were carried out. It is unclear whether fitness training after a traumatic brain injury improves physical fitness. There is not enough evidence to understand the effect of fitness training on other important outcomes. Whilst fitness training appears to be well attended by people with traumatic brain injury, particularly when supervised, and there is no evidence of harm, further well-designed studies are required before we can draw any definite conclusions. In the absence of high quality evidence, health professionals may be guided by pre-exercise screening checklists to ensure the person with traumatic brain injury is safe to exercise, and to set training parameters using guidelines established by the American College of Sports Medicine for people who have suffered a brain injury.
Evidence is current to September 2015. We found five studies with 403 participants, each of which compared two or three methods of guiding fluid therapy. These methods include 'usual care' (whereby staff use changes in basic measurements, such as heart rate, to decide for themselves how much fluid to give), 'protocols using standard measures' (whereby staff use changes in basic measurements when giving fluid according to a formal set of rules) and 'advanced haemodynamic monitoring' (whereby staff use invasive equipment, such as specialized blood pressure monitoring devices placed into arteries, to determine how much fluid to give). These trials found no evidence to suggest that using one method instead of another reduces harm, including death, or decreases the number of complications. We found no evidence, when study results were combined, indicating that any method reduced length of hospital stay or time that participants were assessed as medically fit for discharge. Results also showed no difference in the number of participants able to return to normal accommodation after discharge. We found few relevant studies with only a small number of participants. The time difference between the earliest study, published in 1985, and the latest study, published in 2014, suggests that standard practice for managing hip fracture may differ between these studies. We judged one study as having a high risk of bias, and we used the GRADE approach to assess evidence quality as low or very low. Results of the review are applicable only to countries in which the relevant studies were conducted, as 'usual care' may differ in other countries. Current evidence is insufficient to show which method of finding maximum effective fluid levels in people undergoing hip fracture surgery is preferable.
This review concludes that there is a small amount of evidence from studies performed to date that intrathecal baclofen is an effective treatment for reducing spasticity in children with cerebral palsy in the short-term. The effect of intrathecal baclofen on spasticity in children with cerebral palsy over the long term is less clear. Two short-term studies (by the same investigators) demonstrate a reduction in spasticity, but a single, longer term study shows minimal evidence for reduced spasticity with the use of intrathecal baclofen. Two further short-term studies showed reduction in spasticity with the use of intrathecal baclofen, but the authors used inappropriate methods of analysing the data, so it is uncertain whether these results are valid. All these studies had a small number of participants, making the findings less reliable. The research also provides evidence from one short term study and one longer term study (again, by the same investigators), that intrathecal baclofen therapy improves the comfort, ease of care and some aspects of quality of life for children with cerebral palsy. However, the results of the longer term study may have been influenced by both the participants and the investigators being aware of whether they were receiving treatment or allocated to the control group. This same study found that intrathecal baclofen improves gross motor function a little in children with cerebral palsy, but again, these results may have been influenced by the way the study was conducted. Further evidence of the effectiveness of intrathecal baclofen for treating spasticity is needed from other investigators in order to validate these results. There is little evidence from the short-term randomised controlled trials about the safety and economic implications of this treatment when long-term therapy is administered through an implanted device. For the same reasons, we could not reach a conclusion on whether the subsequent need for orthopaedic surgery is altered in children receiving intrathecal baclofen therapy.
Twenty-two trials randomised approximately 6200 people to pioglitazone treatment. The longest duration of pioglitazone therapy was 34.5 months. Unfortunately, the published studies of at least 24 weeks pioglitazone treatment in people with type 2 diabetes mellitus did not provide convincing evidence that patient-oriented outcomes are positively influenced by this compound. The occurrence of oedema was significantly raised. The results of the single trial with relevant endpoints (Prospective Pioglitazone Clinical Trial In Macrovascular Events - PROactive study) have to be confirmed by other independent investigations. Until new evidence becomes available (several large trials are ongoing) the place of pioglitazone in the treatment of type 2 diabetes mellitus remains unclear.  Furthermore, confusion arises due to different labelling of pioglitazone, for example in Europe and the USA. Consumers and physicians need clear guidance and transparent information about which studies exactly are used for the decisions of the relevant drug authorities.
This review looked at all studies where patients were randomized to one of these drugs or placebo, in this period. One class of blood pressure lowering drug, the so-called nitrates, demonstrated reduction in mortality in patients with heart attack. For 1000 patients treated 4 to 8 deaths were prevented during the first 2 days of this acute event. The ACE-inhibitors class also decrease mortality when continued for 10 days (3 to 5 deaths prevented per 1000). No other class of drug showed a reduction in mortality.
In this overview, we used information from about 35,000 participants in about 350 studies to look specifically at the adverse events (unwanted effects) experienced with painkillers, and compared the results with those for placebo (dummy pill). Measuring adverse events is complicated because the particular method used to collect information influences how many adverse events are reported. Most people in the studies had wisdom teeth removed, were relatively young and fit, and were likely to take occasional painkillers. Adverse events may be different in people who are less well, older, or who take painkillers for several days or longer. The results we have showed that for most nonsteroidal anti-inflammatory drugs (painkillers like aspirin, ibuprofen, or diclofenac), paracetamol, and combinations of different painkillers that do not contain opioids (drugs like codeine), adverse events happened to the same proportion of people with painkillers and placebo. With aspirin 1000 mg, opioids, or fixed dose combinations containing opioids, people typically experienced significantly more adverse events than with placebo. A combination of ibuprofen and paracetamol resulted in significantly fewer adverse events than placebo. Serious adverse events were rare, occurring a rate of about 1 in 3200 people. The results are not unexpected for single dose studies, which are likely to be different from the situation when analgesics are taken over the medium or longer term.
This review included 19 studies reporting the outcomes of ACL reconstruction with patellar tendon versus hamstring tendon grafts in a total of 1597 young to middle-aged adults. Many trials used flawed methods that might have affected their results. The limited data available for functional outcomes including patient-rated assessment did not show whether one graft was better than the other. Similarly, there were no differences found between the two types of graft for re-rupture or in the results of an internationally used knee score. All tests for knee stability favoured patellar tendon grafts. Conversely, people had more anterior knee pain and discomfort with kneeling after patellar tendon reconstruction. After patellar tendon reconstruction, more people had some loss in their ability to straighten out their leg at the knee. In contrast, more people had some loss in their ability to bend their leg at the knee after hamstring tendon reconstruction. It is not clear how important these losses in range of motion of the knee were to the patients themselves. The review concluded that the current evidence was insufficient to recommend which of the two types of graft was better for ACL reconstruction.
The review authors summarised information from one clinical trial that compared botulinum toxin to a placebo, to treat tics in adults with Tourette’s syndrome. We found one small study. The study was limited by the number of participants (N = 18), who mainly had mild tics. We are very uncertain about the effects of botulinum toxin injections on reducing tic frequency and severity, and measures of overall well-being. Some participants experienced harms, which included weakness, restlessness, and neck discomfort following the injection. We do not know from the study whether participants who received the injection developed resistance to the botulinum injections, which would make them less effective over time. The evidence is current to 25 October 2017.
This systematic review looked at studies providing selenium supplements to cancer patients and found no clear evidence that selenium supplements improve side effects of cancer therapy. No adverse effects were reported in the studies, but evidence of overdosing, all be it unintentional and selenium intoxication has occurred in several selenium users. More research is needed to find out which doses of selenium supplements can be reasonably used by cancer patients and whether selenium supplements can affect the side effects of cancer therapy.
This review looked for studies that had considered the effectiveness of drugs used to help patients to empty their bladder after surgery. Few studies were found. There is some evidence that introducing an agent called prostaglandin into the bladder can help patients to regain the ability to empty their bladders. There is weaker evidence that drugs called cholinergics, combined with a sedative, can also help. There is a need for more research in this area.
This review was carried out to evaluate whether these methods lead to improved health outcomes for the mother and her baby. The review included three randomised controlled studies that involved a total of 275 women (data reported for 271) with PPROM at up to 34 weeks' gestation. All three studies were from the USA. They each investigated different methods of fetal assessment, so no meta-analysis could be conducted. Instead, the review reported the results of each individual study. One study compared weekly endovaginal ultrasound scans where the probe is placed inside the vagina versus no assessment, one compared an amniotic fluid test to measure levels of fetal lung surfactant with no assessment, and one compared a daily 'nonstress test' (recording the fetal heartbeat) with daily modified biophysical profiling (recording the fetal heartbeat as well as estimating the volume of amniotic fluid surrounding the baby). In each study, there were few statistically significant differences between groups in outcomes for the mother, fetus or neonate. The overall quality of the evidence was poor, because participants knew which group they were in. More studies are needed to assess the benefits and harms of fetal assessment methods for improving neonatal and maternal outcomes in women with PPROM before firm conclusions can be drawn.
The review of trials found 56 studies involving 3257 children. Alarm interventions reduce night-time bed wetting in about two thirds of children during treatment, and about half the children remained dry after stopping using the alarm. Alarms take longer to reduce bedwetting than desmopressin, but their effects continue after treatment in half the children who use alarms. So alarms are better in the long term than treatment with desmopressin or tricyclic drugs. Overlearning (giving children extra fluids at bedtime after successfully becoming dry using an alarm) and dry bed training (getting children to go to the toilet repeatedly and changing their own sheets when they wet) may reduce the relapse rate. There are no serious side-effects, which can occur with drug treatment. However, children need more supervision and time from other family members at first. There was not enough evidence with which to compare alarms with other non-drug treatments. Because some of the studies were of poor quality, better research comparing alarms with other treatments is needed, including follow-up to measure relapse rates.
We searched medical databases up until February 2014 to find studies comparing warmed fluids with unwarmed fluids and other methods of warming the patient. We found 24 relevant trials with 1250 adult patients undergoing all types of surgery. We did not include studies for which it was intended that the patient would become cold (such as to facilitate heart bypass surgery). We had intended to collect data on which patients became hypothermic (when their body temperature dropped to below 36 degrees Celsius), but no trials reported this, so we collected data on patient temperatures at various time points throughout surgery. We found evidence of moderate quality showing that if patients had the fluids they were given into their veins warmed up, they were about half a degree Celsius warmer and shivered less than those who received unwarmed fluids; however, we were unable to show a significant difference in patients who received warmed fluids to wash out parts of their bodies. We have demonstrated that warming fluids does keep adult patients warmer; however it is unclear whether this alone can make a difference in the severe complications that becoming cold may cause.
The two small studies in this review suggest that Chinese herbal medicine (CHM) may be as effective as gestrinone and may be more effective than danazol in relieving endometriosis-related pain, with fewer side effects than experienced with conventional treatment. However, the two trials included in this review were small and of limited quality so these findings must be interpreted cautiously. Better quality randomised controlled trials are needed to investigate a possible role for CHM in the treatment of endometriosis.
The authors of this systematic review found 54 studies that looked at the error rates of this galactomannan test. These studies compared the results of the galactomannan test with the results of a more elaborate diagnostic workup, so that the percentages of false positive results (patients without invasive aspergillosis, according to the elaborate testing, but with a positive galactomannan test) and false negative results (patients with invasive aspergillosis, according to the elaborate testing, but with a negative galactomannan test) could be calculated. The galactomannan test does not result in a yes/no answer, but in a so-called 'optical density index' (ODI). The authors of the different studies defined the galactomannan test as positive when the ODI was above 0.5, 1.0 or 1.5. Four studies used a different ODI and these were not included in the meta-analysis. Studies and results When an ODI of 0.5 or higher was said to be positive, the galactomannan test missed 22 out of every 100 patients with invasive aspergillosis and it resulted in a false positive test in 15 out of every 100 patients without invasive aspergillosis. When an ODI of 1.0 or higher was said to be positive, the galactomannan test missed 29 out of every 100 patients with invasive aspergillosis and it resulted in a false positive test in 10 out of every 100 patients without invasive aspergillosis. When an ODI of 1.5 or higher was said to be positive, the galactomannan test missed 37 out of every 100 patients with invasive aspergillosis and it resulted in a false positive test in only 7 out of every 100 patients without invasive aspergillosis. Limitations The studies showed variable results and had small numbers of patients with invasive aspergillosis.
The review of trials found that NSAIDs can cause small, temporary negative effects on the kidneys in adults, but no one in the trials experienced renal failure or serious kidney problems. These results may not apply to children or adults with decreased kidney function
We identified 41 studies (around 13,000 participants) that researched ways of helping teenagers to quit smoking. These studies were of mixed quality and looked at various methods for stopping smoking, including one-to-one counselling, counselling as part of a group, methods using computers or text messaging, or a combination of these. Four studies used drug treatments such as nicotine patches. Most studies recruited participants from schools, and 29 of the studies were carried out in North America. Although some programmes showed promise, especially those that used group counselling and those that combined a variety of approaches, there was no strong evidence that any particular method was effective in helping young people to stop smoking. Trials differed in how they measured whether a person had quit smoking, and many trials did not have enough participants for us to be confident about wider application of the results. Medications such as nicotine replacement and bupropion were not shown to be successful with adolescents, and some adverse events were reported, although these events were generally mild and findings were based on studies with small numbers of participants. Based on these findings we cannot currently identify a programme for helping adolescents to stop smoking that is more successful than trying to stop unaided. The quality of evidence was low or very low for all of the outcomes in this review. This is because of issues with the quality of some of the studies, the small number of studies and participants for some outcomes, and the differences between the studies.
In July 2018 we searched for clinical trials where mirtazapine was used to treat fibromyalgia in adults. We found three studies with 606 participants. Studies were seven to 13 weeks long. They compared mirtazapine 15 mg to 45 mg daily against a fake medication (placebo). There was no difference between mirtazapine and placebo for any primary outcome: mirtazapine and placebo reduced pain by 50% in two of 10 people (low-quality evidence). Only one single serious adverse event was available for evaluation of safety (very low-quality evidence). Three of 10 participants with mirtazapine and two of 10 participants with placebo dropped out of the trial due to side effects (low-quality evidence). Mirtazapine reduced pain by 30% or more in five out of 10 people, compared with three out of 10 with placebo (low-quality evidence). It was also better for average pain intensity (low-quality evidence) and sleep problems (low-quality evidence). Mirtazapine was not better than placebo in reducing fatigue, depression, or improving health-related quality of life (low-quality evidence). Mirtazapine and placebo were no different in how many participants experienced a side effect (low-quality evidence). People dropped out at the same rate with mirtazapine and placebo or because they felt the drug did not work (low-quality evidence). For some side effects, mirtazapine was worse than placebo. This was true for drowsiness (4 out of 10 with mirtazapine, 1 out of 10 with placebo), weight gain (2 out of 10 with mirtazapine, 0 out of 10 with placebo), and high liver enzymes (1 out of 10 with mirtazapine, 0 out of 10 with placebo) (low-quality evidence). Two of the studies were of poor quality. We rated the quality of the evidence using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High quality evidence means that we are very confident in the results. We judged that the evidence was mostly of low-quality, which means that while the research provides some indication of the likely effect, the true effect may be substantially different. The main issues were poor study quality, decisions about the types of people included in the studies, risk of important information not being published, and sometimes low numbers of events.
We looked for studies lasting at least two months, in which it was decided at random whether a person received a mucolytic drug or a placebo. We did not include studies involving children or people with other breathing conditions such as asthma and cystic fibrosis. We found 38 studies to include in our review. These studies included a total of 10,377 adults with COPD or chronic bronchitis. The studies used a variety of mucolytic drugs, including N-acetylcysteine, carbocysteine, and erdosteine and lasted from two months to three years. Mucolytics were taken by mouth between one and three times per day. These studies measured several different outcomes to find out if the drug was useful, including flare-ups, hospital admissions, quality of life, lung function, and side effects. We found that people taking mucolytic drugs were less likely to experience a flare-up compared to those taking placebo. Approximately eight people would need to take the drug for nine months for one extra person to avoid having a flare-up. This result was based on 28 studies involving 6723 people. However, the studies carried out a longer time ago (1970s to 1990s) show greater benefit than those carried out more recently. Shorter studies also seemed to show more benefit than longer studies. This could be because the newer trials were larger and may be showing that mucolytics are less beneficial than the earlier studies showed. Or it could be that only studies that showed mucolytics as beneficial were published before the 2000s, when there was a push to report all trial results regardless of whether or not they showed benefit. People taking mucolytics had fewer days of disability (i.e. days when they could not do their normal activities) every month, but this was quite a small difference - less than half a day per person per month. They were also approximately one-third less likely to be admitted to hospital, although this result is based on only five studies that provided this information. Study results suggest that mucolytics do not have an important impact on quality of life or lung function. People taking mucolytics did not experience more unwanted side effects than those taking placebo. But we could not be sure about their impact on death during the study period because only 37 deaths occurred amongst the 3527 participants in studies where deaths were measured and reported. We are moderately confident about the results we have presented. Our confidence is reduced by the results from individual studies looking quite different from one another and the mix of older and newer studies that we found. Also, in some cases there were not enough data to be sure whether mucolytics were better or worse than, or the same as, placebo. Mucolytics appear to be useful for reducing flare-ups, days of disability, and hospital admissions in people with COPD or chronic bronchitis, and they do not appear to cause more side effects. However, they do not appear to have much impact on quality of life or lung function, and we could not be sure about their impact on death. This plain language summary is current to April 2019.
We included 5 randomised controlled trials including 11,466 participants with minor abnormalities on cervical cytology, treated either with immediate colposcopy or repetitive cytology. The included studies assessed differences in occurrence of cervical precancerous lesions between the two treatments. The results suggested that women attending immediate colposcopy after a single low-grade abnormal cervical cytology test were more likely to have clinically insignificant findings detected than women who were managed with 'watchful waiting'. There were 18 cases of invasive cervical cancer, seven in the immediate colposcopy and 11 in the cytological surveillance groups. The detection rate of clinically insignificant low-grade lesions was higher in the immediate colposcopy group, as was the detection rate of clinically more significant high-grade precancerous lesions (CIN2 or CIN2 or worse) at 18 months, but not by 24 months. The risk of non-compliance was significantly greater for the repeat cytology arm and increased with the length of the follow-up. We graded the evidence as low to moderate quality. HPV DNA testing has been shown to be an effective triage tool for women with minor cervical cytology abnormalities. However, this test is not currently routinely available globally. Therefore, if HPV DNA testing is not available, immediate colposcopy is likely to detect more precancerous lesions earlier than cytological surveillance, but after two years there does not seem to be a difference between the two approaches. Women could be referred for immediate colposcopy after a single low-grade abnormal or borderline cervical cytology test, if compliance with cytological surveillance is expected to be poor. When follow-up compliance is expected to be good, repeat cervical cytology may be offered, as this may reduce the risk of over-diagnosis and over-treatment.
Seven studies were found that addressed this question, including a total of 1728 patients. Continuing blood thinning injections after hospital discharge decreased the risk of both blood clots in the limbs and in the lungs. This review determined that the overall incidence of having a blood clot is reduced from 13.2%, when no post-discharge blood thinner injections are used, to 5.3% when a blood thinner injection is prescribed for at least 14 days following discharge in 30 days follow-up. Both symptomatic and asymptomatic blood clots decreased with the use of prolonged duration blood thinner injections in postoperative patients. No increase in bleeding complications or death, common concerns when blood thinners are used, were observed in patients treated with prolonged duration blood thinner injections. Continuation of blood thinning injections for at least 14 days after abdominal or pelvic surgery reduces the risk of blood clots.
The findings of this review are based on five randomised clinical trials with 290 patients. Phyllanthus was tested versus antiviral drugs, including lamivudine, interferon alpha, thymosin, or thymosin alpha 1 for three months to 12 months. The primary findings of this review are that phyllanthus seemed to have a superior effect on clearance of serum HBeAg at the end of treatment in conventional meta-analysis, but not when trial sequential analysis was applied. Phyllanthus had no significant effect on clearance of serum HBsAg, serum HBV DNA, or HBeAg seroconversion when compared with antiviral drugs. No data were identified on mortality or morbidity, adverse events, quality of life, or liver histology. However, the findings in our review are inconclusive due to the small numbers of patients and outcomes, risk of bias, and the study design. We need more randomised trials to confirm or reject the potential effects of phyllanthus. We advocate that phyllanthus is primarily assessed against placebo. This can be done in randomised clinical trials in which all patients receive antiviral drugs that are known to offer more benefit than harm and the patients are then randomised to phyllanthus versus placebo. If the effect of phyllanthus versus placebo is unequivocally demonstrated in such trials, it may be prudent to assess the effects of phyllanthus versus other antiviral drugs superior to placebo in such trials. The quality of trials regarding conduct and report should also be taken into account.
This review included experimental studies called randomised controlled trials (studies in which participants are assigned to a treatment group based on a random method) that compared the effectiveness of pharmacological interventions (antidepressants) to placebo (inactive treatment in the same form as the active treatment, e.g. a pill). Study participants were adults diagnosed with COPD and depression. What does the evidence from the review tell us? We have identified only four studies worldwide that were eligible for inclusion in our review. This means limited evidence to support the use of antidepressants for the treatment of depression in patients with COPD. Only one study evaluated a tricyclic antidepressant, nortriptyline, finding that it reduced depressive symptoms when compared to a placebo. Three studies evaluated a newer generation class of antidepressants called selective serotonin reuptake inhibitors (SSRIs), finding no evidence for their effectiveness in improving depressive symptoms. Due to the limited evidence, we are unable to make definitive statements about the effectiveness but also safety of antidepressants when used for COPD-related depression. However, SSRIs may increase exercise capacity in patients with COPD. Given that the current findings were based on only four small studies with evidence rated as of very low quality, it is important to interpret our results with caution. What should happen next? Insufficient evidence prevented us from making clear recommendations for doctors, other healthcare professionals, researchers, or policymakers. More studies with better methodological quality and a larger number of participants are needed.
The proportion of participants developing a depression in the upcoming winter was similar in both groups as well as the severity of these depressive episodes. However, the quality of the evidence was very low, so we can draw no valid conclusion if MBCT is really ineffective in preventing SAD or not. The included study reported no information on side effects of the intervention. Doctors need to discuss with patients the advantages and disadvantages of MBCT and other potentially preventive treatments for winter depression, such as other psychological therapies, drug treatments, or lifestyle interventions. As no available studies have compared these treatments, treatment selection should be strongly based on patient preferences and other preventive interventions that are supported by evidence. Review authors recommend that future studies should evaluate the efficacy of different psychological therapies in preventing SAD in larger study samples and should directly compare these interventions versus other preventive treatments, such as light therapy, antidepressants and agomelatine, to determine the best treatment option for prevention of SAD.
This review compared the clinical effects of clozapine with the other atypical antipsychotics. Twenty-seven studies fulfilled the review's criteria and provided data to compare clozapine with antipsychotics such as olanzapine, quetiapine, risperidone, ziprasidone and zotepine. Clozapine was somewhat more efficacious than zotepine. Also, inefficacy of treatment led more frequently to leaving the studies early in the risperidone group suggesting a certain higher efficacy of clozapine. The principal drawback of clozapine were its adverse effects which lead to significantly higher numbers of participants leaving the studies early compared to olanzapine and risperidone. Clozapine was associated with more sedation and hypersalivation than olanzapine, quetiapine and risperidone and with more seizures than olanzapine and risperidone. There was a higher incidence of white blood cell decrease in clozapine groups than olanzapine and more weight gain than in risperidone groups. On the other hand clozapine produced fewer movement disorder than risperidone and less prolactin increase than olanzapine, quetiapine and zotepine.
This review update (up to 26 August 2016) includes two clinical trials that compared antibiotics with placebo for children in the post-acute bronchiolitis phase (> 14 days). The first was reported from Turkey and enrolled 30 infants aged seven months or younger. The second was reported from Australia and New Zealand and enrolled 249 infants aged 24 months or younger. Both trials initiated treatment during hospitalisation for bronchiolitis and provided follow-up for six months post hospitalisation. This review update includes a total of two trials with 249 children (n = 240 completed). Both studies contributed to primary and secondary outcomes, but the quality of evidence was low. Review authors noted no significant differences between treatment groups for our primary outcomes: proportion of children (n = 249) who had persistent symptoms at follow-up, and number of children (n = 240) rehospitalised with respiratory illness within six months; nor for our secondary outcome: proportion of children (n = 240) with wheeze at six months. One study reported bacterial resistance, but only at 48 hours. One study reported adverse events from which all children recovered and remained in the study. Currently, not enough evidence is available to inform whether antibiotics should be used to treat or prevent persistent respiratory symptoms in the post-acute phase of bronchiolitis. Clinical trials are needed to evaluate the efficacy of antibiotics for reducing persistent respiratory symptoms, especially in countries where morbidity of bronchiolitis is high (e.g. indigenous populations).
We found six studies that included 477 kidney transplant patients. The majority of these patients had a kidney transplant from a living donor. The overall quality of the studies was low to average, and the main problem was the small number of studies and the small size of the studies. There was no information on funding source for most of the studies. Compared to normal saline, giving kidney transplant patients solutions that contain less chloride during their transplant operation resulted in lower blood acid levels but did not affect how the transplant kidney worked after surgery, or the number of patients who had high blood potassium levels. Harmful effects were not reported in many studies. In the group of patients who were given lower-chloride fluids, the transplant failed in one patient and one patient rejected the transplant. In the group of patients who were given normal saline, the transplant failed in four patients, and two patients rejected the transplant. However, this is probably an incomplete picture of harmful effects.
We identified 26 randomised clinical trials with a total of 3842 participants. Of these, 23 randomised clinical trials (3693 participants) provided information for one or more outcomes. The trials mainly included participants undergoing liver transplantation for the first time, for various reasons. Funding: 14 trials were funded by pharmaceutical companies who would benefit from the results of the trial; two trials were funded by parties who had no vested interest in the results of the trial; and 10 trials did not report the source of funding. The overall quality of the evidence was low or very low, and all of the trials were at high risk of bias, which means it is possible that the conclusions made could overestimate the benefits or underestimate the harms of a given intervention because of the way the trials were conducted. In addition, because of insufficient information, the results of network meta-analysis are not entirely reliable. Several medical drugs were compared in the trials. We found no evidence of difference in the risk of death or graft loss between the different immunosuppressive regimens based on the network meta-analysis. In the direct comparison, based on a single trial including 222 participants, the risk of death and graft loss was higher with tacrolimus plus sirolimus than with tacrolimus alone. There was no evidence of differences between the various immunosuppressive regimens in percentage of people who developed serious adverse events, percentage of people who developed any adverse events, risk of poor kidney function requiring dialysis or kidney transplantation (kidney dysfunction), prolonged kidney disease, graft rejections requiring treatment, and any graft rejections. The number of adverse events was lower with cyclosporine A than with many other immunosuppressive regimens. The risk of retransplantation was higher with cyclosporine A than with tacrolimus. None of the trials reported number of serious adverse events, health-related quality of life, or costs. There is significant uncertainty as to the optimal maintenance immunosuppressive regimen after liver transplantation; further well-designed randomised clinical trials are required. Future trials should be performed in people who are generally seen in the clinic rather than in highly selected participants and report clinically important outcomes such as death, graft loss, kidney dysfunction, long-term kidney disease, and retransplantation. Such trials should use tacrolimus as one of the control groups. Moreover, such trials ought to be designed in such a way as to ensure low risk of bias and low risks of random errors.
This review assessed evidence from nine randomised, double-blind, placebo-controlled clinical trials, in which there were 906 adults in comparisons of diflunisal (a non-steroidal, anti-inflammatory drug) with placebo for treatment of moderate to severe acute post-operative pain. It is an effective analgesic over the dose range 250 mg to 1000 mg, with a long duration of action. At 1000 mg, the analgesic effect over 4 to 6 hours is as good as the combination of paracetamol 1000 mg and codeine 60 mg in similar studies using the same methods.
We included 10 studies involving 762 participants who were randomly assigned to receive AMBMT alone or in combination with PR or PR alone (mainly unstructured walking training). The quality of included studies was generally poor. Given the quality of available evidence, effects of AMBMT in comparison with PR or of AMBMT added to PR in comparison with PR alone remain inconclusive. One key reason for this is that PR programmes used as comparators had major design flaws, for example, the term 'PR' was uncritically used in the vast majority of studies, and PR was often considered equal to unstructured walking training. This, together with the poor quality of evidence, limits our confidence in the observed effects. Available evidence suggests that when AMBMT was compared to PR alone, larger improvements in disease-specific quality of life were observed with AMBMT, although AMBMT was not superior to PR with regard to dyspnoea (breathlessness). AMBMT added to PR resulted in large improvement in generic quality of life when compared with PR alone, although the addition of AMBMT to PR did not lead to further improvements in disease-specific quality of life. However, before definitive conclusions can be drawn, future research studies comparing AMBMT to PR are needed, and these should follow current PR guidelines for designing comparator interventions, preferably delivered by properly trained professionals with a comprehensive understanding of respiratory physiology, exercise science, and the pathology of COPD.
Physical rehabilitation (interventions based on exercising the body) may have a role, and this review examines the evidence available. This review included 67 trials, 36 of which were conducted in North America, 20 in Europe, and seven in Asia. In total, 6300 participants with an average age of 83 years were involved. Most interventions in some way addressed difficulties in activities of daily living. This review investigates the effects of physical rehabilitation on activities of daily living, strength, flexibility, balance, mood, cognition (memory and thinking), exercise tolerance, fear of falling, death, illness, and unwanted effects associated with the intervention, such as injuries. While variations between trials meant that we could not make specific recommendations, individual studies were often successful in demonstrating benefits to physical health from participating in different types of physical rehabilitation.
In this Cochrane review we found six randomised controlled trials including 198 participants with 250 ulcers. Four of the randomised controlled trials were conducted in Jamaica and two in the USA. These trials included medications or dressings applied directly to the ulcer (topical medications) and medications given orally or intravenously (systemic medications). Given the very different modes of action of these two groups, we treated them separately throughout the review. The topical agents included Solcoseryl® cream, RGD peptide matrix dressing and topical antibiotics. Socoseryl aims to improve the use of oxygen by the skin tissue and so promote wound healing. Topical antibiotics are also used to prevent infection. The RGD peptide matrix is a gel that promotes cell growth. The systemic interventions included arginine butyrate, L-cartinine, and isoxsuprine. Aginine butyrate, given intravenously, is thought to accelerate wound healing, L-carnitine, given orally, is thought to improve tissue hypoxia, and isoxsuprine, given orally as isoxsuprine hydrochloride, is thought to widen blood vessels, so increasing blood flow to an affected wound. One medication, a topical intervention (RGD peptide matrix) reduced ulcer size in treated participants compared to controls. However, this effect should be interpreted with caution given the high risk of bias due to the inadequacies associated with this trial report. The evidence for the use of interventions to treat people with sickle cell disease and chronic leg ulceration is not strong. All randomised clinical trials that we included in this review were associated with a high risk of bias. This systematic review has shown the need for well-designed, high-quality randomised trials to assess the benefits and harms of interventions to improve the healing of leg ulcers in people with sickle cell disease.
We found only one small trial for our review. It included 20 children with beta thalassaemia who were considerably shorter than they should be based on growth charts. Ten of the children were randomly selected to receive daily growth hormone treatment in addition to their usual (standard) treatment and the other 10 children just had their usual treatment. Investigators recorded the height of the children and did blood tests every three months. The trial was conducted over a one-year period. Height velocity is the rate at which a child grows taller and is calculated by measuring the difference in height over a period of time (usually measured as cm per year). In this review, the children who received growth hormone for one year had a higher height velocity (on average 2.28 cm per year more) compared to those who did not receive growth hormone. In other words, those given growth hormone grew modestly faster than those not on growth hormone. The height of a child may also be scored based on standard charts of the population (height standard deviation scores). Using this measurement, children treated with growth hormone had similar scores to those not on growth hormone at the end of one year. None of the 20 children suffered from any side effects. Although, while there was no clear difference between groups in the oral glucose tolerance test at one year, those children on growth hormone therapy had higher fasting blood glucose levels, but these were still within the normal range. The trial did not provide information beyond the one-year period, hence we do not know if the adult height of the children in the trial was affected by growth hormone therapy in any way. There were no trials in people with thalassaemia which examined the effects of growth hormone therapy over a longer period, at different dosages or in different age groups; neither were there any trials studying the effect of growth hormone therapy on adult height or general well-being (quality of life). Overall, we considered the quality of evidence for the outcomes described above (short-term growth and side effects) to be moderate, but we had a major concern that there was only a small number of participants. Based on moderate quality evidence from one small trial, the use of growth hormone may modestly improve some measures of growth. However, there was no information on final height or quality of life. More trials are needed before a clear conclusion can be drawn on the overall benefits and risks of using growth hormone in people with thalassaemia.
Routine outcome monitoring of CMHDs using PROMs was not shown conclusively to be helpful in analyses combining study results, either in terms of improving patient symptom outcomes (across 12 studies), or in changing the duration of treatment for their conditions (across seven studies). It was not possible to analyse changes in drug treatment or referrals for further treatment as only two studies reported these. Similarly, health-related quality of life, social functioning, adverse events, and costs were reported in very few studies. More research of better quality is required, especially in primary care where most CMHDs are treated. Studies should include people treated with drugs as well as psychological therapies, and should follow them for longer than six months. As well as symptoms and length of treatment, studies should measure possible harms, quality of life, social functioning, and the costs of monitoring.
Three studies involving 146 participants were included in this review. All three studies compared palliative care delivered in home visits versus usual care for people with MS. Two studies included only participants with MS. The third study (Ne-PAL) included participants with MS and other neurodegenerative diseases. In all three studies, interventions focused on assessment and management of symptoms and end-of-life planning. We did not find studies that compared different types of palliative care with each other. We are uncertain about differences between palliative care versus usual care for the following outcomes assessed at long-term follow-up (> six months post-intervention): change in health-related quality of life, adverse events and hospital admission. The included studies did not assess fatigue, cognitive function, relapse-free survival or sustained progression-free survival. We are uncertain whether palliative care interventions are beneficial for people with MS. There is low- or very low-certainty evidence regarding the difference between palliative care interventions versus usual care for long-term health-related quality of life, adverse events and hospital admission. This evidence is up-to-date as of 31 October 2018.
The evidence is current to August 2014. We found 15 randomized controlled trials on 2242 participants addressing this question. All the trials were performed in individuals who were not seriously ill under elective general anaesthesia. A LMA Classic was used for all studies. Children were enrolled in 11 studies and adults in five studies. None of the trials were of high methodological quality. The risks of complications such as laryngospasm (tight closure of the windpipe preventing effective breathing), and lowering of oxygen content in the blood (desaturation), were similar with early removal and late removal of the LMA. Coughing was less frequent after early removal of the LMA, with a risk of 13.9% as compared to the risk of 19.4% after late removal of the LMA. However, airway obstruction was more likely after early removal, with a risk of 15.6%, as compared to a risk of 4.6% after late removal of the LMA. No data were available on length of stay in the recovery room or hospital, or patient satisfaction. Thus, overall, this systematic review suggests that with the current available evidence, early and late removal of the LMA are comparable in persons undergoing general anaesthesia, and neither is superior in terms of safety. The quality of the evidence that is available is either low or very low for all the outcomes described. This was mainly due to poorly conducted studies, the small number of people that they recruited, and to a lesser extent, some variation in the study results.
Five randomised controlled trials were identified involving 309 people with spinal cord injury. None of the locomotor interventions had a beneficial or harmful effect on the people taking part. In all five studies there were no differences in adverse events or drop-outs between study groups. There is not enough evidence to conclude which locomotor training strategy is most effective in improving walking ability in people with spinal cord injury, or that locomotor training benefits a person's ability to walk over other kinds of rehabilitation.
One randomised clinical trial comparing microwave coagulation with conventional surgery (liver resection) is included in the review: 14 participants received microwave coagulation and 16 participants underwent conventional surgery. The trial was judged to have a high risk of systematic error (ie, overestimation of benefits and underestimation of harms). On the basis of one randomised trial, which did not describe allocation concealment or blinding, and which excluded from analysis 25% of participants after random assignment, evidence is insufficient to show whether microwave coagulation provides any significant benefit in terms of survival or recurrence compared with conventional surgery for participants with liver metastases from colorectal cancer. The number of adverse events, except for the requirement for blood transfusion, which was more common in the liver resection group, was similar in both groups. At present, microwave therapy cannot be recommended outside randomised clinical trials.
We found 63 randomised clinical trials where people with or suspected of a heart attack were randomly allocated to receiving beta-blockers compared with placebo or no intervention. The 63 trials included 85,550 adults with a mean age of 57.4 years. Only one trial was at low risk of bias. The remaining trials were at high risk of bias. The quality of the evidence according to GRADE ranged from very low to high. Fifty-six trials commenced beta-blockers versus control during the acute phase of acute myocardial infarction and seven trials during the subacute phase. We found 33 trials that were fully or partly funded by the industry, 20 trials that did not report their funding source, and 10 trials that were funded by other sources than the industry. Our present review shows that people receiving beta-blockers compared with people receiving placebo or no intervention seem at lower risk of a new heart attack in the acute phase after a heart attack. People receiving beta-blockers also seem at lower risk of dying from any cause and from any cardiac cause at long-term follow-up after a heart attack. Nevertheless, people receiving beta-blockers do not seem to have a lower or a higher risk of dying from any cause or from any cardiac cause in the acute phase after a heart attack. The effects of beta-blockers on all remaining outcomes (serious adverse events according to International Conference on Harmonization - Good Clinical Practice, major adverse cardiovascular events (composite of dying from a cardiac cause and a new non-fatal heart attack), new heart attack at long-term follow-up, quality of life, and angina) are uncertain due to none or sparse data.
Pooling the data from the few studies that were available suggest kidney damage was less likely with a lipid preparation of amphotericin B compared with conventional amphotericin B. It is reasonable to recommend a lipid preparation of amphotericin B, if cost permits. No significant differences have been observed in children when other antifungal agents have been compared. More studies in children evaluating available antifungal are required to further clarify any benefits with regard to the risk of dying, prospects of complete recovery and drug toxicities.
Evidence included in this review is current to April 2015. We included 49 studies involving 4807 participants. Thirteen studies evaluated pelvic endometriosis, 10 studies ovarian endometrioma, 15 studies deep endometriosis (endometriosis deeply situated in tissues in the pelvis) and 33 studies endometriosis at specific sites within the pelvic cavity. All studies included women of reproductive age who were undergoing diagnostic surgery because they had symptoms of endometriosis. None of the imaging methods was accurate enough to provide this information on overall pelvic endometriosis. Transvaginal ultrasound identified ovarian endometriosis with enough accuracy to help surgeons determine whether surgery was needed, and magnetic resonance imaging (MRI) was sufficiently accurate to replace surgery in diagnosing endometrioma but was evaluated in only a small number of studies. Other imaging tests were assessed in small individual studies and could not be evaluated in a meaningful way. Transvaginal ultrasound could be used to locate more anatomical sites of deep endometriosis when compared with MRI, helping surgeons better plan an operative procedure. Endometriosis in the lower bowel appears to be relatively accurately identified by both transvaginal and transrectal ultrasound, by MRI and by multi-detector computerised tomography enema. New types of ultrasound and MRI show a lot of promise in detecting endometriosis but studies are too few to clearly show their diagnostic value. Generally the studies were of low methodological quality, and most imaging techniques were assessed by only a small number of studies. Differences between studies involved how they were run, groups of women studied, ways imaging tests were performed and how surgery was undertaken. Additional high-quality research is needed to accurately evaluate the diagnostic potential of non-invasive imaging tests for endometriosis.
This review found that patients with acute pancreatitis receiving enteral nutrition have fewer episodes of death, systemic infections, multiple organ failure and operative interventions. This data suggests that EN should be considered the standard of care for patients with acute pancreatitis requiring nutritional support.
We found 13 eligible randomised controlled trials (RCTs) involving 701 people for inclusion in this review. There is some evidence that recombinant growth hormone therapy in people with burns covering more than 40% of the total body surface area helps burn wounds and donor sites heal more rapidly and reduce the length of hospital stay, without increased mortality or increased scarring. We found it difficult to assess the quality of these studies due to poor reporting therefore we cannot be completely confident in their results.
A total of 1092 patients were studied in 21 trials. Patients were assigned to a low pressure group (509 patients) or a standard pressure group (583 patients). The choice of treatment was determined by a method similar to the toss of a coin. Most of the trials included low surgical risk patients undergoing planned laparoscopic cholecystectomy. Laparoscopic cholecystectomy could be completed successfully using low pressure in approximately 90% of people undergoing this procedure. No deaths were reported in either low pressure or standard pressure groups in eight trials that reported deaths (total of 434 patients in both groups). Seven trials with 394 patients described complications related to surgery. One participant experienced the outcome of serious adverse events (low pressure group 1/179, 0.6%; standard pressure group 0/215, 0%). Quality of life, return to normal activity, and return to work were not reported in any of the trials. The difference in the percentage of people undergoing conversion to open operation (from key-hole operation) between the low pressure group (2/269; 0.8%) and the standard pressure group (2/287; 0.7%) was imprecise. This was reported in 10 studies. No difference was noted in the length of hospital stay between the groups. Operating time was about two minutes longer (very low quality evidence) in the low pressure group than in the standard pressure group. Currently no evidence is available to support the use of low pressure pneumoperitoneum in low surgical risk patients undergoing planned laparoscopic cholecystectomy. The safety of low pressure pneumoperitoneum has to be established. Only one trial including 140 participants was at low risk of bias (low chance of arriving at wrong conclusions because of study design). The remaining 20 trials were at high risk of bias (high chance of arriving at wrong conclusions because of trial design). The overall quality of evidence was very low. Further well-designed trials are necessary, particularly in high surgical risk patients undergoing laparoscopic cholecystectomy.
A literature search up to December 2013 found 6 trials (containing 6497 participants, 3 trials at low risk of bias). Five of the studies were based in Asia. We found that antibiotics for H. pylori have a small benefit in preventing gastric cancer (51 (1.6%) of 3294 participants given treatment developed gastric cancer subsequently, compared with 76 (2.4%) of 3203 given no treatment or a placebo), but it is unclear whether or not they decrease the number of deaths from the disease, increase or decrease the number of deaths due to any cause, or increase or decrease the number of cases of oesophageal cancer. Data about side effects of treatment were poorly reported. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. One study was at high risk of bias because no placebo was used for the active eradication therapy regimen, and so this part of the trial was unblinded, and the other study was at high risk of bias due to inconsistencies in data reporting at the two points of follow-up. We were unable to resolve this discrepancy despite contacting the original authors. As a result, we downgraded the quality of evidence from high to moderate due to serious risk of bias.
The results of this review support the current practice of topical medication to lower IOP and clearly demonstrate a visual field protective effect. The review authors identified a total of 26 controlled trials that randomised 4979 people with OHT or open angle glaucoma to receive topical medication or a placebo, another topical medication or no treatment for at least a year. Meta-analysis of 10 trials testing different topical medications against placebo or untreated controls showed reduced incidence of glaucomatous visual field defects with treatment for people with OHT. The odds ratio (OR) was 0.62 (range 0.5 to 0.8). The class of beta-blockers (including timolol) had positive but weak evidence for a beneficial effect in protecting against visual field defects (OR 0.7, range 0.5 to 1.0). No single drug showed significant visual field protection in OHT with the evidence available. Medications included beta-blockers, dorzolamide, brimonidine, pilocarpine and epinephrine. From the reports, the majority of trials were of low methodological quality. Local and systemic side effects leading to treatment being stopped were often poorly reported and did not appear to differ between treatment groups. Drop-outs due to side effects occurred with similar frequency in people treated with beta-blocker or placebo and appeared to be less with timolol compared to brimonidine, in three trials.
We searched for new evidence in October 2016 and identified no new randomised controlled trials. From previous updates, this review found limited evidence on the effectiveness of NSAIDs (specifically naproxen) for management of pain caused by endometriosis. This review is also limited in that it includes only one study with data suitable for analysis, and this study involved only 20 women. Available evidence is of very low quality, mainly owing to poor reporting of methods, lack of precision in findings for overall pain relief, unintended side effects of treatment and the need for extra pain relief. The included trial did not report on quality of life, effects on daily activities, absence from work or school or participant satisfaction with treatment. Available evidence does not allow us to conclude whether NSAIDs are effective for managing pain caused by endometriosis, or whether any individual NSAID is more effective than another. As has been shown in other Cochrane reviews, women who use NSAIDs must be aware that NSAIDs may cause adverse effects such as nausea, vomiting, headache and drowsiness. Unless we identify new evidence in the future, we will not update this review again. Evidence was of very low quality owing to risk of bias and imprecision (findings were based on a single small trial).
This is an update of a previous review that included studies on migraine and tension-type headache. This original review has been split in two separate reviews: this update addresses only studies on migraine, while a second focuses on tension-type headache. In November 2014, we identified three new studies. Eight studies were already included in the previous version of the review. Overall, we analysed a total of 585 participants. All the studies had a small number of participants and were conducted over a period of two to three months. Only a few were of high quality. The results suggest that SSRIs and SNRIs are no better than placebo (sugar pill) for reducing the number of migraine attacks. There were no differences in minor side effects between participants treated with SSRIs or SNRIs versus those treated with placebo. SSRIs and SNRIs seem not to offer advantages when compared to other active treatments, specifically the tricyclic antidepressant amitriptyline. The participants treated with SSRIs or SNRIs suffered fewer minor side effects than those who took amitriptyline, however the number of people who stopped taking one drug or the other due to side effects was approximately equal. These results are based on short-term trials (no more than three months), which are not properly sized and feature serious methodological deficiencies. We did not find studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. antiepileptics and anti-hypertensives).
In the present review we assessed the evidence for the efficacy, acceptability and tolerability of duloxetine in comparison with all other antidepressants in the acute-phase treatment of major depression. Sixteen randomised controlled trials (5735 participants) were included. Duloxetine was not more effective than some other new antidepressant agents in the acute-phase treatment of major depression, and it was less well tolerated than escitalopram and venlafaxine as more patients allocated to duloxetine withdrew treatment before study end. However, due to the limited number of studies per comparison these results should be interpreted with caution.
We reviewed evidence from 27 trials covering 21 different herbal treatments in both adults and children from both in-patient and out-patient settings. In general, the reporting of trials was poor. The outcomes measured by the trials varied considerably which made it difficult to compare the results of studies that did look at the same treatment. On the basis of the available evidence it is not possible to show whether any of these herbal treatments can improve asthma symptoms. Further trials of high quality are needed to assess the use of herbal treatments in asthma.
We identified 13 studies: one cluster randomised controlled trial (CRCT) and 12 interrupted time series (ITS) studies, involving 40 hospitals, 51 intensive care units (ICUs), 27 wards and more than 1406 healthcare professionals and 3504 patients, which assessed the impact of different interventions to reduce the occurrence of device-related infections for inclusion in this review. We judged all studies to be at moderate to high risk of bias. The effect sizes were small with the largest median effect for studies addressing central line associated blood stream infections (CLABSIs) occurring immediately after the implementation of an intervention to improve adherence to guidelines, in the majority of studies this change was not sustained over longer follow-up times. The median effect for studies aiming to reduce ventilator-associated pneumonia (VAP) was somewhat greater and was sustained up to 12 months follow-up. The results of six studies that reported adherence/non-adherence with infection control recommendations showed very varying adherence scores ranging from 14% to 98%. The low to very low quality of the evidence of the studies included in this review provides insufficient evidence to determine with certainty which interventions are most effective in changing professional behaviour and in what contexts. However, interventions that may be worth further study are educational interventions consisting of more than one active element and that are repeatedly administered over time, and interventions employing dedicated personnel, who are focused on a certain aspect of care that is supported by evidence e.g. dentists/dental auxiliaries providing oral care. If healthcare organisations and policy makers wish to improve professional adherence to guidelines for the prevention of device-related infections, funding of well designed studies to generate high quality evidence is needed to guide policy.
When researchers want to answer a question they can use an approach called a systematic review, which is intended to examine all of the studies that have been done in a particular area of interest. When examining and summarizing the literature, researchers are expected to determine which of the studies were well-conducted (i.e. high quality) and those that were not. What we do not know enough about is how researchers should conduct the assessments to determine which studies were of high quality. This is important because if the researcher is aware of certain study characteristics (e.g. what journal the study was published in) they may inadvertently assess the study a certain way. For example, if the author of the study is well-known to the assessor, they may be more likely to assume it is of 'high quality'. Our research examines whether blinding researchers to study characteristics makes a difference when the goal is to summarize the literature. We only found a few studies that reported data relevant to our question. The results from these studies were inconsistent, however, the results suggest that it may not make a difference if quality is appraised under blinded or unblinded conditions during a systematic review.
Until 4 August 2016, we did computer searches for studies of hormonal birth control among women who were overweight or obese. We looked for studies that compared overweight or obese women with women of normal weight or body mass index (BMI). The formula for BMI is weight (kg) / height (m)2. We included all study designs. For the original review, we wrote to investigators to find other studies we might have missed. With 8 studies added in this update, we had 17 with a total of 63,813 women. We focus here on 12 studies with high, moderate, or low quality results. Most did not show more pregnancies for overweight or obese women. Two of five studies using birth control pills found differences between BMI groups. In one, overweight women had a higher pregnancy risk. The other found a lower pregnancy rate for obese women versus nonobese women. The second study also tested a new skin patch. Obese women in the patch group had a higher pregnancy rate. Of five implant studies, two showed differences among weight groups. They studied the older six-capsule implant. One study showed a higher pregnancy rate in years 6 and 7 combined for women weighing 70 kg or more. The other reported pregnancy differences in year 5 among the lower weight groups only. Results for other methods of birth control did not show overweight or obesity related to pregnancy rate. Those methods included an injectable, hormonal IUC, and the two-rod and single-rod implants. These studies generally did not show an association of BMI or weight with the effect of hormonal methods. We found few studies for most methods. Studies using BMI rather than weight can show whether body fat is related to how well birth control prevents pregnancy. The methods studied here work very well when used according to directions. The overall study quality was low for this review, especially in the older reports. However, many studies would have higher quality for their original purpose than for the comparisons here.
In reviewing evidence available until November 2013, we found seven eligible studies of children hospitalised with acute asthma; four of these studies (472 children one to 18 years of age) contributed data to the review. Four studies compared the combination of anticholinergics (ipratropium bromide) and beta2-agonists versus the same dose of beta2-agonists alone. Included studies enrolled both girls and boys, with a gender ratio ranging from 59% to 73% males. No additional benefit was noted by adding anticholinergics to β2-agonists in terms of duration of hospital stay in patients compared to those who received beta2-agonists alone. Two of four trials (50%) contributing data were deemed of high methodological quality. No trial reported information on serious adverse events. No statistically significant group difference was noted in other markers of response to therapy, that is, the need for supplemental asthma therapy, time to short-acting beta2-agonists spaced at four hours or longer, asthma clinical scores, lung function and overall withdrawals for any reason. No apparent benefit is derived from adding anticholinergics to beta2-agonists in children hospitalised for an acute asthma exacerbation, that is, beyond initial treatment in the emergency department. No adverse health effects were reported, yet the small number of trials combined with inadequate reporting prevents firm reassurance regarding the safety of anticholinergics. In the absence of trials conducted in the intensive care unit (ICU), no conclusion can be drawn regarding children with very severe exacerbations who are admitted to the ICU. Our findings support the ongoing recommendations provided by national and international guidelines. This review is based on a small number of identified trials conducted in children with acute asthma. All trials contributing to the primary outcome are of high methodological quality, but they are few. As the addition of new trials may change the conclusion, the quality of evidence was downgraded from high to moderate. Additional and larger trials are needed.
The purpose of this review was to assess the evidence for the effectiveness of auditory integration therapy and therapies like it that have been developed to improve abnormal sound sensitivity and autistic behaviours in such individuals. Seven relatively small studies met the inclusion criteria for the review. These often measured different outcomes and reported mixed results. Benefits for participants receiving auditory integration therapy were only reported in two studies, involving 35 participants, for two outcomes. A study of Tomatis therapy did not measure behavioural outcomes and did not find any difference in language development between intervention and control groups. As such, there is no evidence to support the use of auditory integration therapy or other sound therapies at this time.
We searched the medical literature comprehensively, finding two completed trials. Only brief reports (abstracts) of these trials are available. The participants were children aged from five to 15 years with DMD who were able to walk and not able to walk. The treatments were risedronate versus no treatment in one trial (with 13 participants) and whole-body vibration versus a placebo (inactive) device in the other (with 21 participants). We found two completed studies that were potentially eligible for this review, for which full results have not yet been published, and two studies ongoing at the time of the search. These studies are looking at the effects of whole-body vibration (two studies), risedronate, and zoledronic acid. Both completed trials, presented as abstracts only, reported an improvement in bone mineral density in children who received active treatment and no improvement in children in the control (placebo or no treatment) groups. However, the reports did not report results for the comparison of treatment versus control groups, which means that it is not possible to draw conclusions about the effectiveness of either treatment. All children tolerated whole-body vibration treatment. Neither study provided information on adverse events. We know of no evidence from randomised clinical trials to guide use of treatments to prevent or treat osteoporosis and prevent fragility fractures in people with DMD taking corticosteroids. Searches are current to September 2016.
In detailed searches of the medical literature, we found six trials that were suitable for inclusion in our analysis, that together included 460 adults. All six trials were conducted in an approved statistical manner (randomised and double-blinded); however, all had limitations that could lead to an overestimation of efficacy in treating this type of pain. Four were of very small size and five were of short duration, both of which can bias the results of chronic pain trials. Although it was not possible to combine the results of all trials to make an overall conclusion, individually they did all show some, albeit moderate, benefit for venlafaxine in treating neuropathic pain. Usually this benefit was achieved at doses of 75 to 225 mg per day. Known side effects of venlafaxine, including sleepiness, dizziness, and mild gastrointestinal problems, were reported by some studies, but were not particularly problematic. Overall, there is currently an inadequate amount of information available to warrant any change in current prescribing practice and we cannot recommend venlafaxine as a first-line treatment for neuropathic pain. However, it is a reasonably well-tolerated drug and may be of some benefit in people who cannot tolerate other antidepressants or anticonvulsant drugs that are more widely prescribed to people with neuropathic pain. Larger clinical trials may provide more robust evidence for the effectiveness of venlafaxine in treating neuropathic pain.
Four randomised controlled trials with a combined total of 1439 women assessed the effects of induction of labour for women managed as outpatients versus inpatients. Out of a total of four studies, the induction agents differed in two studies, whereas the remaining two studies evaluated the same induction agent (vaginal PGE2). The limited information from these trials did not support more successful induction within 24 hours, shorter length of stay in hospital or differences in need for further induction or the mode of giving birth. The information available was limited and it is, therefore, not yet possible to determine whether induction of labour is effective and safe in outpatient settings.
The evidence gathered in this review was considered of low quality. We downgraded the quality of the evidence because we had concerns about the risk of bias in the included studies and imprecision of the results. It was possible that patient prognosis or clinicians' preferences influenced the allocation of participants to receive one or another medication. This process should be implemented by chance to allow a fair comparison between the therapies. We were not confident that staff implementing the trials were not aware of which treatment participants were receiving, and it was possible that the incomplete reporting of data could have affected the estimates. The detection of HIT throughout the trials was also problematic, and we were not confident that it was performed adequately. The results may be correct, but they may be changed by future research.
This update reviews the randomised controlled trial evidence of a class of drugs called the neuraminidase inhibitors in treating and preventing influenza in children. Neuraminidase inhibitors work against influenza by preventing viruses from being released from infected cells and subsequently infecting further cells. Oseltamivir (Tamiflu), an oral medication, and zanamivir (Relenza), an inhaled medication, are currently licensed, whilst laninamivir is undergoing Phase III clinical trials. Neuraminidase inhibitors are usually prescribed to patients presenting with flu-like symptoms during epidemic periods to reduce symptoms or prevent spread of the virus. We included six treatment trials involving 1906 children with clinically suspected influenza and 450 children with influenza diagnosed on rapid influenza testing. Of these 2356 children, 1255 had proven influenza infection confirmed on laboratory testing. We also included three trials of neuraminidase inhibitors for the prevention of influenza, which involved 863 children who had been exposed to influenza. This review found that treatment with neuraminidase inhibitors was only associated with modest clinical benefit in children with proven influenza. Treatment with oseltamivir or zanamivir shortened the duration of illness in healthy children by about one day. One trial demonstrated that the new neuraminidase inhibitor drug laninamivir reduces duration of illness by almost three days in children with oseltamivir-resistant influenza. The effect of neuraminidase inhibitors in preventing transmission of influenza was also modest; 13 children would need to be treated to prevent one additional case. Neuraminidase inhibitors are generally well tolerated but there will be one extra case of vomiting for every 17 children treated with oseltamivir. Other side effects such as diarrhoea and nausea were no more common in children treated with neuraminidase inhibitors compared to placebo. There is currently no high-quality evidence to support targeted treatment of 'at risk' children (with underlying chronic medical conditions) with neuraminidase inhibitors.
This review aimed to evaluate the strategies that encourage people with cystic fibrosis to participate in daily physical activity. There were four included studies with a total of 199 participants which investigated the effect of exercise training on participation in physical activity. These were mostly conducted in children. The study methods and results were not clearly reported, so it was difficult to tell if the results were influenced by the way in which participants were assessed, or the nature of the outcomes reported. The training programmes ranged from 18 days to three years. In two studies the exercise training programmes were supervised and in two studies they were unsupervised and home-based. Due to differences in the study design and the outcomes measured, we could not combine data from different studies. None of the studies reported any improvement in participation in physical activity when the exercise training lasted less than six months. There was very limited evidence that using a home-exercise programme, for at least six months after receiving activity counselling and exercise advice, improved participation in physical activity in people with cystic fibrosis. No training program showed significant effects on quality of life. It is unknown whether strategies such as health coaching or Internet-based advice may help promote regular participation in physical activity in people with cystic fibrosis.
This review examines the efficacy and safety of the use of various Ayurvedic treatments for diabetes mellitus. We found seven trials which included 354 participants (172 on treatment, 158 on control, 24 could not be classified). All these studies included adults with type 2 diabetes mellitus. Six studies tested five different types of herbal mixtures (proprietary drugs) and only one tested 'whole system' Ayurvedic treatment. The duration of treatment ranged from three to six months. One study each of Diabecon, Inolter and Cogent DB (proprietary herbal mixtures) found significantly lower glycosylated haemoglobin A1c (HbA1C) levels at the end of the treatment period compared to controls. Two studies of Diabecon, and one study of Cogent DB (proprietary herbal mixtures) found significantly lower fasting blood sugar levels at the end of the study period in the treatment group. No deaths were observed in these trials and side effects did not differ significantly between intervention and control groups. One study of Pancreas tonic reported no significant change in health-related quality of life. No study reported on or was designed to investigate diabetic complications, death from any cause and costs. Despite positive results in some studies, and absence of serious side effects, firm conclusions cannot be drawn due to weak methods and small number of participants in the evaluated studies. Further research is needed to assess the efficacy of these treatments. Ayurvedic physicians generally use a mixture of various herbs or proprietary preparations along with diet, exercise and mode of living. The treatments are usually individualised taking into account the balance of three 'doshas'. It is possible that the interventions in the trials analysed have not replicated actual Ayurvedic practice but only assessed some components individually.
Until then, the reviewers propose that the use of antidepressants which have no known life threatening side effects remain more attractive. The review sets out the required methodology for effectively studying these substances in proper controlled studies.
We searched scientific databases to find all the new evidence up to 26 January 2016. This review updates a previous one published in 2006. We included 15 studies that compared different types of fixed and removable retainers and different durations of wear. There were 1722 participants including adults and children. Nine studies took place in a hospital or university setting, five studies in specialist practice and one in a National Health Service Clinic. The studies evaluated four comparisons: removable retainers versus fixed retainers (three studies); different types of fixed retainers (four studies); different types of removable retainers (eight studies); and one study compared a combination of removable and fixed retainers, use of an adjunctive procedure and a positioner. We also found four ongoing studies and four studies await classification. Most of the evidence was of low quality. One small but well conducted study that compared full-time and part-time wear of thermoplastic retainers did not find evidence of a difference in stability (moderate quality evidence). There is not enough high quality evidence to recommend any one approach to retention over another. Further high-quality studies are needed.
We identified four trials that included 758 participants. We excluded studies in which the participants had complications. Two of the four included studies in this review were small and the quality of the evidence was low to moderate. We do not know if acetaminophen is effective for reducing common cold symptoms or its adverse effects. We cannot either 'recommend' or 'not recommend' its use in common practice because we do not have enough well-designed trials to reach a conclusion. There is a need for more high-quality studies to determine the effectiveness of acetaminophen in relieving common cold symptoms.
This review considers the available evidence on the procedures of spinal decompression (widening the spinal canal or laminectomy), nerve root decompression (of one or more individual nerves) and fusion of adjacent vertebrae. There is moderate evidence that instrumentation can increase the fusion rate, but any improvement in clinical outcomes is probably marginal. The effectiveness of intra-discal electrotherapy (IDET) remains unproven. Only preliminary results are available on disc replacement and it is not possible to draw any conclusions on this subject.
This review finds that giving antibiotics is not supported by conclusive evidence. The review identified four trials involving 852 GBS positive women. Three trials, which were more than 20 years old, compared ampicillin or penicillin to no treatment and found no clear differences in newborn deaths although the occurrence of early GBS infection in the newborn was reduced with antibiotics. The antibiotics ampicillin and penicillin were no different from each other in one trial with 352 GBS positive women. All cases of perinatal GBS infections are unlikely to be prevented even if an effective vaccine is developed.
Atrial fibrillation after heart surgery is a common complication that has been associated with poor outcomes. We reviewed the literature to better understand the role of preventative interventions for this condition. By combining the results of 118 studies with 17,364 participants, we are able to gain a better understanding of the evidence behind each of these interventions. All of the interventions studied were effective in reducing the occurrence of atrial fibrillation, length of hospital stay, cost of hospital treatment and may be effective in reducing the risk of stroke. The interventions did not have an effect on death after heart surgery. It was not possible to analyze the adverse events associated with the medications studied in this review, but these should be considered by clinicians when choosing an appropriate intervention for their patients. Furthermore, differences in the design between the studies combined in this review may complicate interpretation of these results.
We included five trials with a total of 122 participants. In these trials the length of treatment ranged from two to eight weeks. Four of the trials compared inhaling before to inhaling after the airways had been cleared and found no overall difference in clinical outcomes. However, in children with well-preserved lung function, inhaling of dornase alfa after airway clearance techniques was better for small airways function. However, this did not affect quality of life or other outcomes. In the remaining trial, morning versus evening inhalation had no impact on lung function or symptoms. Therefore, for many people with cystic fibrosis, the timing of dornase alfa inhalation (before or after airway clearance or the time of day) can be based on practical reasons or individual preference. Apart from one trial published only in abstract form, the quality of the evidence ranged from low to very low. This was due to issues relating to group allocation, blinding, incomplete reporting of outcome data and the the limited age range of participants.
We identified 66 trials comparing group-based programmes to other types of support, or comparing different types of group programme. The most recent search was in May 2016. In 13 trials (4395 participants) people in the control conditions were provided with a self-help programme. There was a benefit for the group-based approach, with the chance of quitting increased by 50% to 130%. This means that if five in 100 people were able to quit for at least six months using self-help materials, eight to 12 in 100 might be successful if offered group support. We judged the quality of this evidence as moderate, because studies did not report methods in enough detail to exclude possible bias. There was also evidence of a benefit of group support compared to advice and brief support from a healthcare professional (14 trials, 7286 participants), although the difference was smaller and more variable. We rated this as low-quality evidence, because of the variability as well as possible risk of bias. There was also low-quality evidence of a benefit in studies that did not provide the control group with any help to quit (9 trials, 1098 participants). Six trials (980 participants) compared group format with individual face-to-face counselling; there was no sign that one approach was more helpful than the other. The remaining studies compared different types of group programmes; typically they did not show differences, so it is not possible to show which components of group-based programmes are most helpful.
We searched four computerised databases and five trial registers to 20 January 2017. We looked for all trials that randomly allocated participants to one treatment or another (randomised controlled trials (RCTs)), and included adults (aged 18 years or older) with early non-small cell lung cancer (stages I to III), confirmed by laboratory testing of a sample of the tumour. We found nine RCTs, which included nearly 5000 participants who had received surgery or curative radiotherapy, and were randomly allocated to receive either immunotherapy or no further treatment. We found that giving immunotherapy, mainly vaccine-based (aiming to activate the host immune system to induce human immune response to tumour-specific antigens), after surgery or radiotherapy did not, on average, make people live longer. We did not find any results that could tell us whether the addition of immunotherapy improved the quality of life, but it seemed that those who were given vaccine-based immunotherapy may have experienced, on average, more side effects. At the moment, there is no evidence to support or refute giving immunotherapy (mainly vaccine-based) to people with localized NSCLC (stages I to III). RCTs are in progress that are testing new, more promising immunotherapy drugs (e.g. checkpoint inhibitors). The evidence we found about overall survival and progression-free survival was high quality. When we looked for evidence about how many patients lived to one, two, three, or five years, it was only moderate or low quality, because the RCTs were not very well done, and their results did not agree with each other.
We included eight studies with 233 male participants with haemophilia A or B (of any severity), aged eight to 49 years. Length of study ranged from four to 12 weeks. Several types of exercise programs were studied, including stretching, strengthening with weights, exercise in water, treadmill walking, and exercise bicycle. Some studies compared participants who did one type of exercise with those who did another type of exercise; other studies compared an exercise group with a control group that did no exercise. There were no data relating to our primary outcomes which indicated whether bleed frequency changed after an exercise program. There were no adverse effects measured or reported. Quality of life was not measured. Regarding our secondary outcomes, improvements were seen in balance, joint health, and pain. Walking distance was the only functional status measured. In an unplanned additional analysis, improvements were seen in the range of motion, biceps perimeter; strength, and knee circumference. These small studies showed more improvements in pain, muscle strength and joint range of motion in exercise groups than in control groups. Studies that included functional activity, such as walking on a treadmill, showed more improvement than exercise alone. Exercise in water seems to be more effective than land exercise in relieving joint pain in adults. Four studies included only males with moderate haemophilia. Three studies included all severities of haemophilia and in one, participants used clotting factor prior to participating. Two studies included males with both haemophilia A and B; three studies did not specify type. Only one study limited their participants to those with severe haemophilia, and these also had osteoporosis. It is not clear whether the same results would be achieved if only males with severe haemophilia A were studied. The results should be interpreted with caution due to the quality of the evidence; we judged that all but one of the outcomes assessed were low or very low quality, due to small sample sizes and potential bias.
The evidence is current to August 2019. We found two studies assessing add-on losigamone for focal epilepsy, which recruited a total of 467 participants aged over 18 years. Both studies assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal epilepsy. The results of this review showed that participants taking losigamone as an add-on treatment were more likely to reduce their seizure frequency by 50% or more in the short term; however losigamone was associated with more treatment withdrawal side effects than placebo. The most frequent adverse event caused by losigamone was dizziness. We assessed one study as being of good methodological quality while the other was of uncertain quality. We judged the overall quality of the evidence for the outcomes assessed as moderate.
We selected studies that assessed the effect of dietary calcium interventions such as supplementation or food fortification on blood pressure in normotensive people of all ages. The last search date was October 2014. This review analysed information from 16 trials (3048 participants). We found that an increase in calcium intake slightly reduces both systolic and diastolic blood pressure 1.43 mmHg lower and 0.98 mmHg lower respectively. This effect was higher with doses of calcium above 1000 mg/day. Systolic blood pressure was reduced by 1.14 mmHg with doses of calcium 1000 to 1500 mg/day and by 2.79 mmHg with doses of calcium equal to or over 1500 mg/day. We noted a reduction in blood pressure in both men and women and at ages from 11 to 82 years old, but the reduction was greater among younger people. Systolic blood pressure was reduced by 2.11 mmHg among those less than 35 years and by 0.96 mmHg among those 35 years or older. None of the studies reported adverse events. We need further research to determine the ideal dosage of supplementation and whether it is more effective and safer as part of the diet or as a supplement. We found high quality of evidence for systolic and diastolic blood pressure in both men and women. The quality of evidence was also high for participants 35 years or older and moderate for younger people. The quality of evidence was high for doses of calcium of 1000 to 1500 mg/day and was moderate for lower or higher doses. Five of the 16 trials were industry funded.
We included twelve randomised trials (577 participants) in this updated review. Most of the included trials studied foot ulcers in people with diabetes (10 trials). For diabetes-related foot ulcers, we found that HBOT seemed to improve the chance of healing in the short term (up to six weeks), but not with longer term follow-up. HBOT may reduce the number of major amputations in people with diabetes who have chronic foot ulcers. For chronic wounds caused by disease to the veins of the leg, we found that HBOT may reduce the size of wounds. For chronic wounds caused by lack of blood supply through the arteries or chronic pressure ulcers, we found no evidence to confirm or refute any effects of HBOT. We could not assess safety as none of the trials included in our review reported whether there were any major adverse events. This plain language summary is up-to-date as of 23/1/15
We reviewed randomized trials of reducing pain during IUC insertion through 22 June 2015. We found 33 studies with a total of 5710 women. Most were recent trials. Methods tested were nonsteroidal anti-inflammatory drugs (NSAIDs), lidocaine, misoprostol, and other treatments. Lidocaine 2% gel had no effect on pain during IUC insertion (three trials) or pain with tenaculum (type of forceps) placement (two trials). Other types of lidocaine showed some effect. Pain score for IUC insertion was lower with a lidocaine and prilocaine cream and with 10% lidocaine spray. With 4% lidocaine gel, pain scores were lower shortly after IUC insertion. With 1% lidocaine injection, pain score at tenaculum placement was lower compared with no intervention. With four misoprostol trials, the pain score with IUC insertion was higher for misoprostol versus placebo ('dummy' treatment). Two other trials showed higher pain scores with misoprostol versus placebo either at IUC insertion or after. However, another study showed the misoprostol group had less serious IUC-insertion pain. Also, the misoprostol group rated the insertion more favorably. In analysis of four trials, cramping was more likely with misoprostol versus placebo. Within two other trials, the misoprostol group was more likely to have shivering, headache, or abdominal pain. In one study, the misoprostol group was less likely to choose the treatment again or recommend it. Pain score during IUC insertion was lower for the opioid tramadol versus naproxen. In the same trial, pain was lower for naproxen versus placebo. The naproxen group was less likely than the placebo group to rate the experience as unpleasant and not want the treatment in the future. In another trial, women with several naproxen doses had lower pain scores after IUC insertion than the placebo group. Overall, the effectiveness results were of moderate quality, having come from single studies. Trials of lidocaine, tramadol and naproxen showed some effect on reducing pain from IUC insertion.
Individual randomised controlled trials have demonstrated that antidepressants are effective for OCD. This review summarises all the available evidence for one class of antidepressant drugs, the selective serotonin re-uptake inhibitors (SSRIs) (including citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) compared to placebo in the treatment of OCD in adults. The review included 17 studies (3097 participants), and showed that SSRIs were effective in reducing the symptoms of OCD. Based on 13 studies (2697 participants), the review showed that people receiving SSRIs were nearly twice as likely as those receiving placebo to achieve clinical response (defined as a 25% or more reduction in symptoms). Indirect comparisons of effectiveness suggested that although individual SSRI drugs were similar in their effectiveness, they differed in terms of their adverse effects. The most common adverse effect reported by participants was nausea. Further studies involving head to head comparisons between different SSRI drugs are required to obtain more reliable information on differences between SSRIs, both in terms of effectiveness and adverse effects.
We conducted a wide search for reports of clinical trials of treatments for nerve damage in leprosy. We found five clinical trials that met our criteria, involving 576 people with leprosy. Two of the included trials compared prednisolone with placebo. One of these trials, with 84 participants, recruited people who had mild abnormality of feeling of less than six months' duration and the other, with 95 participants, assessed treatment effects in people with abnormal nerve function of 6 to 24 months' duration. A third trial, with 334 participants, compared three 12-month corticosteroid regimens for severe type 1 reactions. Type 1 reactions are episodes in which nerves become inflamed. The fourth trial (21 participants) compared a low dose of prednisone with a high dose of prednisone for people with damage to the ulnar nerve (a nerve in the arm). The fifth trial (42 participants) compared intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone in people with a type 1 leprosy reaction or abnormal nerve function of no more than six months' duration. There was no important difference in improvement in nerve function between people treated with prednisolone or with placebo after one year, according to two trials. More people on a three-month course of prednisolone failed to respond to treatment and required extra corticosteroids compared to people on either a high-dose or a low-dose regimen of five months' duration. The trials comparing corticosteroids with placebo and a trial comparing intravenous methylprednisolone and oral prednisolone with intravenous normal saline and oral prednisolone found no differences in the occurrence of adverse events between groups. We considered the quality of the evidence to be moderate to low. Although trials were well conducted and designed, they were largely small and did not always use proven measures to capture the effects of corticosteroids. The evidence in this review is up to date to June 2015.
Other Cochrane reviews provide clear evidence that giving anti-D immunoglobulin (anti-D) within 72 hours of the birth to a Rh-negative mother of a Rh-positive baby and during the third trimester reduces Rh antibody formation in future pregnancies. The chances of developing Rh antibodies may also be reduced if anti-D is given to Rh-negative women following a spontaneous miscarriage or a dilatation & curettage (D&C) for incomplete miscarriage after 12 weeks. However, our review only identified one poor quality randomised controlled trial (involving 48 women) that considered anti-D administration after therapeutic D&C or spontaneous miscarriage for preventing Rh alloimmunisation (development of antibodies in response to antigens from a non-self protein). The included study did not report any data on the review's primary or secondary outcomes. More high-quality research is needed in this field.
The review included 31 randomised controlled trials which compared SSRIs with placebo in a total of 4372 women who were clinically diagnosed with PMS. SSRIs were found to be effective for reducing the overall symptoms of PMS and also for reducing specific types of symptoms (psychological, physical and functional symptoms, and irritability). SSRIs were usually taken for about two weeks before the start of the menstrual period (the luteal phase) or every day (continuously). Both regimens appeared to be equally effective, although more research is needed to confirm this. Adverse effects were more common in the women taking SSRIs than in those taking placebo. The most commonly occurring side effects were nausea and decreased energy. The review authors calculated that nausea is likely to occur as a drug side effect in approximately one out of seven women with PMS taking a moderate dose of SSRIs, and lack of energy is likely to occur as a drug side effect in approximately one out of every nine women. The overall quality of the evidence was rated as low to moderate, the main weakness being poor reporting of methods in the included studies. At least 21 of the studies received funding from pharmaceutical companies.
We searched for trials which looked at the health outcomes for women and babies after specific interconception care, and compared the outcomes for standard care (with no interconception care of this type). Our search identified one trial which has yet to issue a full set of results, plus two further trials; one of these is still underway and the other has yet to be published. Because there are no studies currently available, there is not enough evidence at present to say if interconception care for women with a history of GDM can help to improve the health of mothers and their infants. More high-quality studies are needed, which assess both short- and long-term health outcomes for women and their babies, as well as evaluating the impact on the health services.
This review aimed to compare cholesterol-lowering dietary interventions either in combination with each other or alone. These interventions included adding omega-3 fatty acids or plant sterols or plant stanols or soya proteins to diet. Fifteen trials were included in this updated review. The included trials had either a low or unclear risk of bias for most of the domains used for risk assessment. All the trials were short term and the majority were cross-over in design. For most of the comparisons there was no significant difference in the various intervention strategies when compared to cholesterol-lowering diet. However, for total cholesterol levels, serum low density lipoprotein (LDL) concentrations, a significant benefit was obtained with plant sterols. However, before drawing any conclusions, methodological problems with pooling results from cross-over trials should be considered. There is a need for long-term trials with parallel group design to assess the potential benefits and harms of a cholesterol-lowering diet.
This review included 17 studies (1586 children). Long-term antibiotics (equal to or more than six weeks) almost halved the risk of further infections. There was not enough information to know if antibiotics reduced acute otitis media with perforation or chronic suppurative otitis media (chronic perforation), or improved long-term outcomes. Antibiotics did not appear to be a frequent cause of significant side effects (for example, allergic reactions or diarrhea). Parents must balance these potential side effects plus the cost and inconvenience associated with antibiotics against the likely benefits of treatment. Antibiotic resistance from the long-term use of these drugs is also an issue which should be considered, particularly for children with recurring infections.
This review found that a single intranasal dose was effective in relieving migraine headache pain and associated symptoms of nausea, sensitivity to light, and sensitivity to sound. Pain was reduced from moderate or severe to no pain by two hours in approximately 2 in 10 people (24%) taking sumatriptan 10 mg, compared with about 1 in 10 (10%) taking placebo. Pain was reduced from moderate or severe to no worse than mild pain by two hours in 5 in 10 people (50%) taking sumatriptan 10 mg, compared with approximately 3 in 10 (32%) taking placebo. In addition to relieving headache pain, sumatriptan also relieved symptoms of nausea and sensitivity to light and sound by two hours in about half of those who took it, compared with about one-third of those who took placebo. The 20 mg dose had greater efficacy, but may be associated with more adverse events, most of which were of short duration and mild or moderate in severity.
Nine studies enrolled 351 participants. The studies used different formulations of the enzyme, Agalsidase alfa or beta, and compared them to placebo (a 'dummy' treatment) or to each other. Comparison was also made in regard to different dosing schedules. Two studies comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma. The combined effects were not significant between the treatment and placebo groups. The study that reported pain and pain-related quality of life showed an improvement for participants receiving treatment over the six-month observation period. Death was not an outcome in either study. One of the three studies comparing agalsidase beta to placebo reported on globotriaosylceramide and showed improvement in kidney, heart and composite results. There was no significant difference for death and no studies reported on pain. Only two studies compared agalsidase alfa to agalsidase beta. One of them showed no significant difference for any adverse events such as dyspnoea, hypertension and gastrointestinal symptoms - these are not adverse events as gastrointestinal problems are actually a symptom, as may be hypertension in the context of renal disease. Two studies compared different dosing schedules of agalsidase alfa. No differences were found among the schedules for self-assessed health state or for pain scores. In summary, studies comparing enzyme replacement therapy to placebo show significant results in regard to microvascular endothelial deposits of globotriaosylceramide and in pain-related quality of life. There is, however, no evidence identifying if the alfa or beta form is superior, though included trials were small in sample size. With regards to safety, adverse events (i.e., rigors, fever) were more significant with agalsidase beta as compared to placebo. From the information available in most of the study reports, we were not able to clearly judge whether all volunteers had equal chances of being in either of the treatment groups and whether they would have known in advance or during the study which treatment they were receiving.
The evidence is current to April 2013. The review included 20 randomised controlled trials with a total of 1969 premenopausal women with heavy menstrual bleeding for whom non-surgical treatment had not worked. Studies compared GnRH analogues, danazol and progestogens versus placebo or no treatment; GnRH analogues versus danazol, progestogens, GnRH antagonists or dilatation & curettage; and danazol versus progestogens. Four studies performed more than one comparison. Three studies used the newer second-generation surgical techniques for endometrial destruction. GnRH analogues and danazol used before hysteroscopic surgery improve both operating conditions for the surgeon and short-term bleeding symptoms for women (up to 24 months after surgery). GnRH analogues thin the lining of the womb better and more consistently than danazol, although both agents produce satisfactory results. Adverse effects were more common in women taking GnRH analogues or danazol compared with no treatment, and this was especially true with danazol. Adverse effects included menopausal symptoms such as hot flushes, vaginal dryness, hirsutism, decreased libido and voice changes, as well as other side effects such as headache and weight gain. The use of medications to thin the lining of the womb before surgery does not appear to improve heavy menstrual bleeding in the long term (i.e. longer than 24 months). However, only a few small studies followed up with women for longer than 24 months. Also, medications given to thin the womb lining do not provide additional benefit when used with the newer second-generation endometrial destruction techniques, which are being performed increasingly in hospitals. Overall, the quality of the evidence was very low because of risk of bias in the included studies and differences between the studies. The quality of reporting of adverse events was generally poor.
In May 2016, we searched the medical literature and found four studies involving 1253 participants looking at ketoprofen for frequent episodic tension-type headache. Only a fraction of the participants were involved in comparisons between ketoprofen 25 mg and placebo (a dummy tablet). Results were usually reported two hours after taking the medicine or placebo. The International Headache Society recommends the outcome of being pain-free two hours after taking a medicine, but other outcomes are also suggested. Few studies reported these recommended outcomes, so there was limited information to analyse for some outcomes. The outcome of being pain-free at two hours was reported by 27 in 100 people taking ketoprofen 25 mg, and in 16 out of 100 people taking placebo, meaning that only 11 in 100 people benefited because of ketoprofen 25 mg (low quality evidence). The outcome of being pain-free or having only mild pain at two hours was reported by 66 in 100 people taking ketoprofen 25 mg, and in 38 out of 100 people taking placebo (moderate quality evidence), meaning that 28 in 100 people benefited because of ketoprofen 25 mg. About 14 in 100 people taking ketoprofen 25 mg reported having a side effect, which was slightly more than with placebo (7 in 100 people) (low quality evidence). Most side effects were mild or moderate in intensity. No side effects were serious. Ketoprofen 25 mg was not different from paracetamol 1000 mg for any measure of headache relief (moderate and low quality evidence), but was associated with more side events (low quality evidence). The quality of the evidence for being pain-free at two hours was low quality, and for having mild pain at two hours was moderate quality. Moderate quality evidence means that we are reasonably confident about the results. Low quality evidence means that we are not very certain about the results and they could change with more information.
Five of the RCTs evaluated the efficacy of IVIg for the treatment of exacerbations or worsening (the former being usually more severe than the latter). One RCT of IVIg versus placebo, which included 51 participants, showed some evidence of the efficacy of IVIg for treating myasthenia gravis with worsening weakness. Two trials, the first of which included the first 87 and the second 84 participants, showed no significant difference between IVIg and plasma exchange. In the first of these trials there was a high risk of bias because the assigned treatments were not hidden. A trial including 33 participants showed no difference in efficacy between IVIg and a corticosteroid (methylprednisolone) but did not recruit enough participants to detect an effect, so there is insufficient evidence to favour IVIg over corticosteroids in moderate exacerbations. Another trial, which included 168 participants, showed no evidence of superiority of IVIg 2 g/kg over IVIg 1 g/kg on the change of myasthenic muscle score (MMS) after 15 days (MD 3.84; 95% CI -0.98 to 8.66). Two RCTs evaluated the efficacy of IVIg for the treatment of moderate or severe myasthenia gravis. One compared, in 12 participants, IVIg and plasma exchange. The second, with 15 participants included, compared IVIg and a placebo. Both are underpowered and the first at some risk of bias, so no conclusion could be drawn from these two trials. There is no evidence from RCTs nor from other trials to determine whether IVIg improves function or reduces the need for steroids.
This review looked at the effectiveness of dietary advice given by dietitians to lower blood cholesterol, compared with the effectiveness of dietary advice given by other types of health professional or using self-help resources. The review found that advice by dietitians to lower blood cholesterol was more effective than that of doctors (in the short to medium term), but possibly not more effective than using self-help resources. There was no evidence to suggest that dietary advice given by dietitians was more effective than that given by nurses.
We reviewed the published research on this treatment to investigate how effective and safe it is. Unfortunately, we identified only one randomized controlled trial comparing LDR-BT versus RP. The results were considerably prone to bias. Important survival outcomes were not reported. Due to lack of research studies, it has not been proven whether patients treated with this procedure live longer than patients treated with treatment alternatives. In this single study, after the intervention, a rise in prostate-specific antigen (PSA) was similarly likely to occur after LDR-BT and RP, but this finding does not resolve the question of whether cancer was truly present again in both groups. Urinary incontinence was less frequent after LDR-BT and urinary irritation was less frequent after RP at a short-term follow up at 6 months. No results were reported at 12 and 60 months. Significant differences after long-term follow up were not identified for patient-reported outcomes. At present, the question whether LDR-BT is a favorable treatment compared to other treatment alternatives in patients with localized prostate cancer remains unanswered.
This review wanted to find out if there was evidence to support that there is any difference between ziprasidone and the other atypical medications. Because of the large number of people that dropped out of the studies it is difficult to draw any firm conclusions, however, people taking ziprasidone did not do as well regarding their symptoms, as those taking olanzapine and risperidone and perhaps amisulpride, but they were less likely to gain weight.
We included all randomised controlled trials (a type of study in which participants are assigned to a treatment group using a random method) that assessed whether those who received individualised caseworker discharge planned management (the intervention group) had better outcomes compared to those who received usual care (the control group). We considered the number of hospital readmissions, emergency department visits, and/or unscheduled general practitioner visits following discharge. The evidence is current to 15 November 2017. We found four studies that included 773 children aged 14 months to 16 years. All the studies involved children with asthma. The programme used for the discharge plan differed among the studies, but all were delivered by a trained asthma educator (lay health worker or nurse specifically trained on educating patients with asthma). The studies followed the children for 2 to 14 months after discharge. We could only include data from two studies in a combined analysis (i.e. the meta-analysis), as the other two studies also enrolled children who were not hospitalised, and we could not obtain data specific to the children who were hospitalised and one of those studies included children with acute wheezing illness( no previous asthma diagnosis); the data specific to this review could not be obtained. In this review involving children hospitalised with asthma flare-ups, trained asthma educator-led and structured discharge plans that included follow-up support (compared to the control group) reduced the number of hospital readmissions for acute asthma. No clear benefit was seen on future emergency department or general practitioner visits for acute asthma. Data on cost-effectiveness, length of stay of future hospitalisations, and adherence to discharge medications were not available. One study reported quality of life and found no differences between the intervention and control group. There were no studies relating to other long-term breathing diseases. Individual caseworker-assigned discharge planned management, as compared to non-caseworker-assigned management, may prevent readmissions to hospital for asthma flare-ups in children. However, the current evidence is limited to only two studies in children with asthma. Further studies are needed in a broad range of long-term breathing diseases in childhood. We considered the quality of the evidence to be moderate for the outcome of hospital readmissions and low for the outcomes of future emergency department visits and general practitioner consultations for asthma flare-ups.
This review of trials sought to assess these benefits and harms. Twenty-two out of 29 included studies (1793 women) contributed data to this review. There were some differences that favoured regional anaesthesia, for example, less blood loss. The evidence on the differences in pain relief was difficult to evaluate. There were not enough participants to assess the very rare outcome of mortality for the mother, which may be an important aspect. None of the trials addressed important outcomes for women such as recovery times, effects on breastfeeding, effects on the mother-child relationship and length of time before mother feels well enough to care for her baby. As there is insufficient evidence on benefits and adverse effects, women are most likely to choose anaesthesia for caesarean section, depending on whether they wish to be awake or asleep for the birth.
The evidence for this review is current as of 1 October 2018. We included three trials that compared dilute formula milk (half-strength, double-volume) with full-strength formula milk. The trials involved 102 preterm or low birth weight infants; two were conducted in the USA and one in India. The trials were small (14, 38 and 50 infants, respectively) and conducted between 25 and 30 years ago. The quality of two trials was judged to be poor due to insufficient information being provided in the trial publications, but judged to be moderate in the third trial (of 38 infants). None of the trials assessed necrotising enterocolitis as an outcome. Infants receiving dilute formula (half-strength, double-volume) experienced fewer episodes of feeding intolerance and achieved full energy intake earlier than infants receiving full-strength formula (20 kcal/oz (˜ 68 to 70 kcal/100 mL)). Feeding intolerance Two measures of feeding intolerance (abdominal distension and episodes of gastric residuals) were reported across the trials. Two trials (88 infants) provided data for abdominal distension and gastric residuals. Infants fed dilute formula experienced 19% (CI 16% to 23%) fewer episodes of abdominal distension (> 2 cm), equivalent to 0.67 episodes per infant in the half-strength group compared to 0.83 episodes in the full-strength group. It was not possible to combine data on gastric residuals but both trials reported fewer episodes of gastric residuals in the dilute formula group. The third trial (14 infants) only reported that there was no difference between the groups with respect to these two outcomes. Time to establish full enteral feeding In two trials (88 infants) infants receiving dilute formula experienced a 22% (CI 16% to 28%) reduction in the number of days required to reach an adequate energy intake (420 joules/kilogram), equivalent to 8 days in the half-strength group compared to 10.3 days in the full-strength group. In exclusively formula-fed preterm or low birth weight infants, low-certainty evidence shows that diluted formula may lead to an important reduction in the time taken to attain adequate enteral fluid and energy requirements, without increasing indicators of feeding intolerance. The clinical importance of the reduction in episodes of feeding intolerance is unclear. These findings are based on three small, old trials that may be of less relevance to current practice. A lack of data on other important outcomes, such as the incidence of necrotising enterocolitis and weight gain, limits the usefulness of the studies.
We found seven randomised controlled trials comparing hysterectomy with salpingectomy to hysterectomy without salpingectomy. They included a total of 350 women undergoing a hysterectomy for benign conditions of the female reproductive tract. The evidence is current to January 2019. We found no studies that reported ovarian cancer incidence after hysterectomy with salpingectomy to hysterectomy without salpingectomy. The number of complications that occur after hysterectomy is generally very low. This means that only a few complications occurred in the trials included in this review and we were unable to make a good comparison of complication rates. We found no evidence for any difference in onset of menopause after hysterectomy with salpingectomy. Our results suggest that the AMH concentrations after hysterectomy with salpingectomy would be between 1.89 pmol/L lower and 0.01 pmol/L higher than after hysterectomy without salpingectomy. The minimum difference in AMH concentration (0.01 pmol/L) represents no difference in the onset of menopause. The maximum difference in AMH concentration (1.89 pmol/L) shows that menopause could occur up to 20 months earlier after hysterectomy with salpingectomy compared to hysterectomy without salpingectomy. This result is calculated from the average decline of AMH per year. The evidence was of very low to low quality. The main limitations in the evidence were a low number of complications, meaning no comparison could be made, and differences in outcome measures of the included studies. Also, the total numbers of included studies and included women were low.
We conducted a systematic review and meta-analysis of randomised controlled trials of corticosteroids for treating eosinophilic meningitis. The evidence is current to December 2014. We found only one randomised controlled trial that matched our criteria. This trial included 129 patients (63 in the treatment group, prednisolone 60 mg/day, divided into three doses for two weeks and 66 in the control group, placebo). However,19 patients were lost to follow-up. The included study showed that the median time to resolution of headaches was lower in the group treated with prednisolone (10.5 days versus 25 days) and the number of patients who still had headaches after 14 days was lower in the prednisolone group compared to the control (9.1% versus 45.5%). There were statistically significant differences, which favoured the treatment group, in other outcomes including the frequency of acetaminophen (paracetamol) use (median of number of times used) amongst those who still had headaches after 14 days of prednisolone treatment and the mean time until complete disappearance of headache. The number of patients who needed repeat lumbar puncture was also smaller in the treatment group. There were no reported adverse effects from prednisolone in the treatment group. Corticosteroids significantly help relieve headache in patients with eosinophilic meningitis, who have a pain score of four or more on a visual analogue scale. Given the lack of allocation concealment and blinding (especially in a trial with subjective outcomes), and the attrition (loss of participants), we graded our evidence as moderate quality.
We reviewed all clinical trials in preterm babies that gave corticosteroids after the first week after birth and provided data on rates of bronchopulmonary dysplasia later in the newborn period. This review of trials indicates that giving corticosteroids to infants at least seven days after birth produces short-term benefits in reducing the need for assisted ventilation and the rate of bronchopulmonary dysplasia, perhaps also reducing death during the first 28 days of life. However, high doses in particular are associated with short-term side effects such as bleeding from the stomach or bowel, higher blood pressure, and difficulty tolerating glucose. In contrast with early use of corticosteroids (in the first week of life), we found little evidence of long-term complications and uncertainty regarding long-term problems. It seems wise to limit late use of corticosteroids to babies who cannot be weaned from assisted ventilation, and to minimise the dose and duration of any course of treatment. Overall the quality of evidence supporting our conclusions was high.
We looked for studies that compared children receiving methylphenidate at any dose to placebo (a dummy pill which looks like methylphenidate but has no known effects). We were most interested in investigating the effect of the drug on symptoms of ADHD (inattention, impulsivity and hyperactivity) and ASD (impairments in social interaction and communication, and repetitive, restricted or stereotypical behaviours), but we also looked for information on side effects, caregiver well-being, the need for special schooling or institutionalisation, and children's overall quality of life. What are the main results of the review? We found four studies involving 113 children aged 5 to 13 years and comparing methylphenidate versus placebo. We included two studies with five-year-old children because we were unable to separate the data for those aged six years and above, and all other participants were in our target age range. In all of these studies, children took different doses of methylphenidate (low, medium or high) for one week and placebo for another week, and their caregivers (including parents, teachers and clinicians) rated their symptoms at the end of each week. Children who could not tolerate methylphenidate in the test-dose week (where a dose of medication is given to test the safety and tolerability of the drug) did not participate in the study. All of the studies took place in the USA. We found that methylphenidate may improve hyperactivity, as assessed by parents and teachers, in the short term. Teachers also tended to report an improvement in children taking methylphenidate in relation to inattention, social interaction, repetitive behaviours, and overall ASD symptoms. However, the studies only lasted for about four weeks, so we do not know if there are any benefits or risks in the long term. There was not enough evidence to say whether methylphenidate has any effect on impulsivity or communication. Teachers and clinicians tended to report more improvement than parents. We cannot be confident about these findings, mainly because parents and teachers may have recognised which treatment the children were on. The size of the improvement was not very large, except in the case of hyperactivity, where it was probably large enough to really notice the difference. Most of the improvements, except for the improvements in hyperactivity and inattention, could have happened by chance even if methylphenidate is not really effective. We cannot say anything about the likelihood of any harmful effects from methylphenidate, partly because children who had harmful effects prior to the studies, or in the test-dose phase, are less likely to have participated in the studies. How up-to-date is this review? The evidence is current to November 2016.
We found four studies (277 participants) that assessed the effectiveness of stool transplantation for the treatment of adults with active UC. We did not find any randomized studies that assessed stool transplantation in participants with CD or in children. In addition, we did not find any studies that assessed maintenance of remission in participants with inactive IBD. Two of the identified studies were conducted in Australia, one in Canada, and one in the Netherlands. The dose, route, frequency, volume, type of donor, and severity of disease of recipients varied among the studies. Combined results from four studies including 277 participants indicated that stool transplantation increased rates of resolution of symptoms (also termed clinical remission) of UC patients by two-fold compared to controls. At 8 weeks after transplantation, 37% (52/140) of participants in the stool transplant group were in remission compared to 18% (24/137) of participants in the control group. Combined data from the same four studies showed similar rates of serious side effects. Seven per cent (10/140) of the stool transplantation group had a serious side effect compared to 5% (7/137) of the control group. Serious side effects included worsening of ulcerative colitis that required intravenous steroids or surgery; infections such as Clostridium difficile and cytomegalovirus, small bowel perforation, and pneumonia. The incidence of side effects were similar in both stool transplant and control groups and included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Data from three included studies showed that stool transplantation helped improve UC when the assessment of disease resolution was made by the appearance of the intestinal lining when visualized with an endoscope. We rated the overall quality of the evidence using the GRADE approach, which takes into account the type of studies, methodological flaws within studies, the consistency in reporting of results across studies, method of measurement of effect of intervention and statistical confidence in the summary estimates. Based on these criteria, we judged the overall quality of the evidence for most of the outcomes to be low based on a small number of events and participants and inconsistency of results. Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious side effects. Thus, no firm conclusions can be drawn regarding the benefits and harms of stool transplantation in people with active UC. We did not find any studies that addressed treatment of CD with stool transplantation or studies that assessed stool transplantation in children with IBD. In addition, we did not find any studies that assessed long-term maintenance of remission in participants with inactive IBD. More studies are needed to enhance the knowledge about use of stool transplantation for treatment of IBD.
The authors of this Cochrane review questioned whether resuscitation with room air resulted in fewer deaths or disabilities than 100% oxygen. After searching the literature, they found five studies. There were a total of 1302 infants in these studies; 24% of them were premature. In the studies, fewer babies died when resuscitated with room air than with 100% oxygen. Many of the babies resuscitated with room air also got some oxygen as a supplement, making it difficult to compare the two groups. There were also other problems with the way the studies were carried out. The authors of the Cochrane review concluded that there is not enough evidence to recommend room air over 100% oxygen, or vice versa.
The three randomized trials compared PCV versus VCV in a total of 1089 adults with ALI/ARDS from 43 ICUs in five high-income countries. None of the trials were industry-funded. The evidence is current to October 2014. We could not be sure whether the proportions of patients who died in hospital were very different between those treated with PCV and with VCV. For every 1000 persons treated with VCV, 636 deaths were reported. On the basis of our results, we could expect to see between 210 fewer deaths and 13 more deaths with PCV. We found that effects on mortality in the ICU and on mortality at 28 days were similarly uncertain. Our results include the possibility that VCV or PCV could be better for reducing the duration of ventilation or the development of traumatic lung damage caused by ventilation (barotrauma). None of the studies provided reliable information regarding to what extent failure of other organs would be impacted by the type of ventilation, nor did they provide information on differences in infection risk or quality of life following discharge from intensive care. The overall evidence for mortality was of moderate quality. For outcomes such as duration of ventilation, barotrauma and organ failure, evidence was limited by the small numbers studied, the different methods used in the studies or differences in reporting of results, which made interpretation difficult. Available evidence is insufficient to confirm whether PCV offers any advantage over VCV in improving outcomes for people with acute lung injury on ventilator machines. More studies including a larger number of people given PCV and VCV may provide reliable evidence on which more firm conclusions can be based.
This review aimed to determine which treatment approach was better for women with subfertility and endometriomata who were undergoing assisted reproductive technology (ART). Four trials were identified. A gonadotropin-releasing hormone (GnRH) agonist showed a positive treatment effect on the ovarian response to controlled ovarian hyperstimulation (COH) and the number of mature oocytes retrieved compared to GnRH antagonist. The evidence for surgery was limited but aspiration was associated with a greater ovarian response than expectant management (a wait and see approach). Further randomised controlled trials of interventions for the management of endometrioma in women undergoing ART are required.
We identified and included seven trials in which 249 surgical trainees with limited previous laparoscopic experience received either box model training in addition to their standard apprenticeship training (122 trainees) versus standard apprenticeship training alone (127 trainees). The choice of whether the trainees received supplementary box model training was made in a random method similar to the toss of a coin. Six trials were conducted in USA and one trial in Canada. After supplementary box model training or standard training, the performance of the trainees was evaluated on their first operation after supplementary box model training and during the first operation in humans after an equivalent time after standard training. Different trials assessed the performance in different operations and all these operations were minor to moderate operations. Three trials including 168 trainees reported the complications that the patients developed during or immediately after the operation. There were no deaths in either group in 168 operations performed by 168 trainees and we could not tell whether laparoscopic box model training led to major complications (one major complication in one patient operated by a trainee who underwent standard training out of 86 operations performed by trainees who underwent standard training as compared with no major complications in 82 operations performed by trainees who underwent box model training). None of the trials reported patient quality of life. One trial reported a small reduction in operating time of just over six minutes in the supplementary box model training group. The remaining trials did not report operating time. In one trial, the proportion of patients who were discharged as day-surgery was significantly higher in the supplementary box model training group (24/24 (100%)) compared with the standard training group (15/26 (57.7%)). The remaining trials did not report the proportion of people who stayed overnight. None of the trials reported trainee satisfaction. The operating performance as assessed by surgical experts was significantly better in the supplementary box model training group compared with the standard training group. None of the trials compared box model training compared with animal model training or compared with different methods of box model training. Laparoscopic box model training appears to improve technical skills compared with standard surgical training in trainees with limited previous laparoscopic experience. It may also decrease operating time and decrease the proportion of patients who require overnight stay in the first hernia repair operation that the trainee performed after box model training. However, the duration of the benefit of box model training (ie, whether such benefit continues in subsequent operations) is unknown. Only one trial including 50 trainees was at low risk of bias (no risk of arriving at wrong conclusions because of favouritism by the researchers). Overall, the quality of evidence was very low. Further well-designed trials with less risk of bias because of poor study design or because of chance are necessary. Such trials should assess the long-term impact of box model training on clinical outcomes.
We identified 26 studies studying 8835 participants. Risk of bias was high in 17, unclear in six studies and low in three studies. The use NSAIDs had uncertain effects on the incidence of AKI compared to placebo. Quality of evidence was very low due to inconsistencies between the two studies. One study was stopped early by the data monitoring committee due to increased rates of AKI in the NSAID group and both of these studies examined much lower doses of NSAIDs than would usually be used for pain relief. NSAIDs may slightly increase serum creatinine (a marker of kidney function which rises in kidney failure) compared with placebo. Quality of evidence was low. These studies only included fit, healthy patients. No reliable conclusions could be drawn from the studies examining urine output due to the different methods of measuring this. It is uncertain whether the use of NSAIDs leads to an increased need for renal replacement therapy (dialysis), more deaths, or increased length of hospital stay. NSAIDs have uncertain effects on the rates of AKI when used in patients with normal kidney function following surgery. It is uncertain whether NSAIDs increase the need for dialysis. The available data therefore does not confirm the safety of NSAIDs in patients undergoing surgery. Further studies including patients with other health problems are required.
Three studies with 386 participants were included in the review. All participants were subfertile women undergoing assisted reproduction. Their characteristics differed across studies. One study included women having their first IVF cycle, with no blood clotting disorder. Another study included women with at least one blood clotting disorder. The third study included women with at least two previous unsuccessful assisted reproduction treatment cycles. In all cases a daily injection of low molecular weight heparin was given to women from the time of egg collection or embryo transfer during assisted reproduction. Control groups received placebo or no treatment. There were no issues with source of funding in any of the studies. The evidence is current to May 2013. Key Results It is unclear whether peri-implantation heparin in assisted reproduction treatment (ART) cycles improves live birth and clinical pregnancy rates in subfertile women. Although there was some suggestion of benefit, this disappeared when an alternative method of analysis was used. Heparin had side effects such as bruising and bleeding, but no conclusions could be drawn regarding its safety because none of the studies reported comparative data on adverse effects. The evidence does not justify the use of heparin except in well-designed clinical research trials. Such trials are a priority. Quality of Evidence The evidence was of low or very low quality, mainly due to imprecision, inconsistency and inadequate reporting of advere events. Further well-designed randomised controlled trials with larger sample sizes are needed to clarify the possible role of heparin in assisted reproduction.
In this review we included all studies that compared three-day therapy with longer treatment (five days or more). Three days of treatment were adequate to achieve symptomatic relief for most patients, but it appears that longer therapy is better in terms of bacteria elimination from the urine, no matter what antibiotic is used. Longer therapy for UTI is related to higher rate of adverse reactions to the antibiotics used. Pending further research, it could be considered for women in whom eradication of bacteria in the urine is important.
We identified 16 eligible trials enrolling a total of 1251 infants through searches updated to 8 September 2016. These trials provide moderate-quality evidence that unrestricted feeding with nutrient-enriched (vs standard) formula does not have important effects on growth and development up to about 18 months of age. Long-term growth and development have not yet been assessed. Current recommendations to prescribe nutrient-enriched formula for preterm infants after hospital discharge are not supported by available evidence.
We looked at six studies that involved 599 people aged between 18 and 80 years that assessed exercise before flu vaccination. Exercises included walking or using a treadmill (endurance) and biceps curls and lateral raises (resistance) activities that ranged from 25 to 50 minutes per session. People in five studies did one session of exercise on the day of vaccination; in one study people exercised eight weeks before vaccination. Exercise was supervised in three studies. People not undertaking exercise (control group) were assessed after periods of quiet rest. Three studies did not report study funding sources; one received support from a drug company that donated flu vaccine, one from a professional society, and another from government agencies. We found no differences in numbers of people who caught flu or developed complications between people who exercised and those who did not before flu vaccination. Only one study reported how many people developed flu after exercise and vaccination. No studies reported complications related to flu; only one reported adverse events. None reported numbers of working or other days lost due to flu. No beneficial differences were reported between exercise and no-exercise groups before vaccination. Small numbers of people who were involved in the studies, limitations in study design, and different exercise types meant we were unable to draw robust conclusions about any benefits of exercise before vaccination. There appears to be no benefit or harm from exercising before receiving flu vaccination. Evidence quality was very low or low. More robust study designs that include enough people to enable assessment and analysis of findings may help to determine if exercise before vaccination can reduce numbers of people who develop flu or complications. We found that exercising before influenza vaccination is neither beneficial nor harmful. Small number of people in each included study, many types of exercises, and focus on blood examination instead of participant-centred outcomes strongly influenced our findings.
From these studies, we know that clonidine applied to the skin probably gives little benefit to patients with PDN, but we cannot be sure of this. Clonidine may provide partial pain relief to one out of eight people treated with it. We do not know how clonidine applied to the skin works in other neuropathic pain conditions. Treatment with the drug for short periods probably will not cause side effects, but we do not know from the studies if clonidine is safe for long-term use. Researchers have reported no differences in the total numbers of side effects among people taking TC or placebo. The most important message from this review is that clonidine applied to the skin may give partial pain relief for only some people with PDN.
The findings in this review are based on three clinical trials with 390 patients. The drug cyclosporin A was tested against placebo. The primary findings of the review are that cyclosporin A has no effect on survival or progression of the disease (cirrhosis development). Patients given cyclosporin A experienced more adverse events than patients given placebo, especially renal dysfunction and hypertension. There was significant improvement in itching (pruritus) and liver biochemistry, which were secondary outcome measures. We cannot recommend the use of cyclosporin A outside randomised clinical trials.
The Information Specialist of Cochrane Schizophrenia ran an electronic search (up to 30 March 2017) for trials that randomised people with schizophrenia who were not responding to their initial antipsychotic treatment to receive either an increased antipsychotic dose or switch to a different antipsychotic drug. Nine hundred and two records were found and checked by the review authors. Only one trial met the review requirements and provided usable data. Data were reported for the number of participants who responded to treatment, the general mental state of participants at endpoint of the trial and the presence of negative symptoms at endpoint. There were no data available for any other outcome. No clear difference between increasing the dose of the antipsychotic drug and switching to a different antipsychotic was shown. The available evidence was extremely limited and of very low quality. The results of the present review show that there is no good-quality evidence to help clinicians decide between increasing the antipsychotic dose or switching to a different antipsychotic drug for people not responding to their initial antipsychotic treatment. Therefore, no clear conclusions can be drawn. Larger, well-designed trials are needed.
Review authors found 17 randomised controlled trials of iNO in the preterm newborn through searches updated until January 2016. These trials studied preterm babies with very different baseline characteristics; therefore, we decided to divide them into three groups: (1) trials of babies treated in the first few days of life with severe lung disease, (2) studies providing treatment after the first few days of life to babies who were at increased risk of chronic lung disease and (3) trials providing routine early treatment for babies who experienced respiratory distress. In none of the three groups of trials did iNO improve survival, and no consistent evidence suggests that iNO decreases lung injury. Studies in group 1 (early rescue treatment) reported a 20% increase in severe bleeding into the brain. This finding was close to statistically significant. The quality of the evidence was moderate to high. This review of studies found that inhaled nitric oxide therapy does not appear to improve the chances of improved outcomes for preterm infants with pulmonary disease. When given to babies who were very ill, iNO did not seem to help and may have contributed to increased risk of intracranial haemorrhage.
We included in our review 557 participants from three studies; 319 received smart technology to support self-management, and 238 received face-to-face verbal/written or digital information and education about self-management. The average age of participants was 64 years. Our review included more men than women because the sample from one study consisted of war veterans, most of whom were men. Participants used the technology for just four weeks in one study to six months in the second and four months in the third, which also reported data at 12 months. Technology used in these studies included smart phones or PCs. People who received smart technology showed greater improvement in self-management and quality of life and increased physical activity compared with people who received face-to-face/digital and/or written support over a four-week to six-month period. Also, hospital admissions and exacerbations of COPD did not differ between those who used smart technology and those who did not. Only one study provided information about people who stopped smoking and reported no differences between groups. We found only three studies all at high risk of bias - that we could include in this review, and we could conduct analysis on only two of our outcomes (quality of life and increased physical activity). As a result, we think that current information does not show clearly whether smart technology is helpful for people with COPD. We recommend further research of high quality that focuses on outcomes relevant to different stages of COPD. Researchers should be clear about how self-management is assessed, should report standard trial outcomes, particularly cost, and should include follow-up for at least one year so they can provide comments on behavioural change and impact of treatment.
The evidence is current to the 7 August 2014. Of the eight studies identified, only one fulfilled the criteria for the review. This study assessed 146 participants over a three-month period. Half the participants took a placebo tablet and half took a garlic tablet during this time. The participants then wrote in a diary when they had symptoms of a cold. The included study found that people who took garlic every day for three months (instead of a placebo) had fewer colds. That is, over the three-month period, there were 24 occurrences of the common cold in the garlic group, compared to 65 in the placebo group. When participants experienced a cold, the length of illness was similar in both groups (4.63 versus 5.63 days). More participants in the garlic group (four) than the placebo group (one) noted a smell when burping, so it is possible that blinding of participants was not adequate. However, other potential biases were well controlled. The only included study is directly relevant to the review question. Although the trial is small, there were enough participants to provide precise, reliable results. There is no evidence that results were selectively reported. However, this was possible as the outcomes do not appear to have been decided in advance. Considering the financial incentive for supplement companies to produce positive trials, it is also possible that trials that showed no effect of garlic were never published. Overall, the quality of the evidence is moderate. Possible side effects in this small trial included odour and a skin rash. More information is needed about the possible side effects of garlic.
The review of trials found there was only limited evidence to support the use of surgery for primary dysmenorrhoea and little evidence for its use in women with endometriosis. No adverse effects were found with UNA but PSN was found to cause treatable constipation. More research is needed.
We searched scientific sources to identify eligible trials and found 11 studies with 862 participants. We found no trials including adults. The identified studies examined three treatments: two trials compared giving a red blood cell transfusion only when the levels of haemoglobin in the blood fell below a certain concentration (known as a restrictive versus a liberal transfusion trigger); two trials compared whether there was a benefit to removing white blood cells (leukocytes) from the transfused red blood cells and seven trials compared methods used to prepare the fluid for the CPB machine. The trials were different in terms of the age of the participants, the type of heart disease and the exact treatment studied so there was been no opportunity to pool data for analysis. All studies did not report on all outcomes (a measure of a participant's clinical and functional status that is used to assess the effectiveness of a treatment, e.g. death, side effects). Key results Our primary outcome was death within 30 days after surgery. Five trials looked at this outcome and found no clear difference in mortality between the treatment arms. Four trials explored other adverse effects following a red blood cell transfusion. A difference in the number of adverse events was only observed for kidney failure: in one trial (with 309 participants), patients receiving cell salvaged red blood cells during CPB were less likely to have renal failure than patients not exposed to cell salvage. Quality of the evidence This review identified only a few, small studies across three interventions. These studies measured many different aspects of red blood cell transfusion in patients having heart surgery so it is difficult to make accurate conclusions about the benefits or risks of red blood cell transfusion for these patients. More research is needed to allow accurate conclusions. Future studies should be bigger and focus on one aspect of transfusion in a specific type of heart disease.
Three studies were identified that met the inclusion criteria. It was not possible to pool the data from the 3 included studies, either because of the different lengths of treatment or choice of different control treatments, or because the outcome measures were not comparable. Two significant results were found but there were no statistically significant differences between validation and social contact or between validation and usual therapy. There were no assessments of carers. All in all there is insufficient evidence from randomised trials to allow any conclusion about the efficacy of validation therapy for people with dementia or cognitive impairment.
Our review assessed the current evidence related to one of those brief tests, the Mini-Mental State Examination (MMSE), in the prediction of decline to dementia in people with cognitive impairments. After an extensive search and analysis of available information, we did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of patients who will convert to dementia in the future.
In March 2018 we searched for clinical trials where ear drops were used to help soften and remove build up of ear wax in patients' ears. We found and included 10 studies with a total of 623 participants. However, only six of these studies provided data with which we could analyse our primary outcome, the proportion of patients with complete ear wax clearance. These six studies included a total of 360 participants, both children and adults (of all ages), with partial or full blockage of the external ear canal with ear wax. The 10 included studies looked at either oil-based drops (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based drops (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), saline (salty water) or water alone, or no treatment. Only one study compared using drops with an active ingredient to not using drops at all. The drops may help increase the proportion of ears cleared of wax from 1 in 20 (if you do nothing) to about 1 in 5 (if you use drops). We did not find any evidence that water-based or oil-based drops were any different to saline or water. However, we also did not find any evidence that water or saline were better than doing nothing. Adverse (side) effects were not common. Fewer than 30 patients reported any adverse events when using the drops and these were mild (such as slight irritation or pain, or unpleasant smell). No serious side effects were reported by any participant. We rated the quality of the evidence from studies using four levels: very low, low, moderate or high quality. High-quality evidence means that we are very confident in the results. Very low-quality evidence means that we are very uncertain about the results. For wax clearance, we rated the quality of the evidence as low. For adverse effects we rated the quality of the evidence as low. We have found that using ear drops when you have a partially or completely blocked ear canal may help to remove the ear wax in your ear. It is not clear whether one type of drop is any better than another, or whether drops containing active ingredients are any better than plain or salty water.
We included 11 trials involving 1069 patients in this review. Most participants in the trials had a low anaesthetic risk. There were no deaths or serious complications in the only trial that reported this information. Overall, 85% of patients (472/554) were discharged as day-procedure laparoscopic cholecystectomy patients and 2% of patients (1/60) required hospital readmission. The reasons for not discharging the patients as day-procedure patients were not described in detail in the trials. The reason for readmission was fever that developed in the patient and which subsequently settled on its own without any treatment. Quality of life was not reported in any of the trials. There was no clear evidence of a difference in the measures of pain intensity between any of the comparisons. Time to return to routine daily activity and to return to work were not reported in any of the trials. There is currently no evidence to support one anaesthetic regimen for day-procedure laparoscopic cholecystectomy over another. All the trials had elements that tended to reduce our trust in the accuracy of the results. Few patients were included in each comparison resulting in a considerable chance of arriving at erroneous conclusions. Randomized controlled trials designed to minimize the risk of arriving at wrong conclusions are necessary to determine the best anaesthetic regimen for day-procedure laparoscopic cholecystectomy, one of the commonest procedures performed in the western world.
This review examined whether cleansing the lung using a natural chemical called surfactant, or another similar fluid, is helpful in MAS. This cleansing procedure is known as lung lavage. Lung lavage with diluted surfactant may help improve the clinical course of infants with MAS, in particular, the likelihood of survival without the need for heart-lung bypass. More trials will be needed to properly evaluate lavage treatment in MAS.
After searching for all relevant studies up to January 2013, we found 108 studies with 10,655 people with osteoporosis. Ninety-nine different Chinese herbal medicines were tested and compared with placebo (three trials), no intervention (five trials) or conventional medicine (61 trials), or Chinese herbal medicines plus conventional medicine were compared with conventional medicine (47 trials). The average length of treatment was 5.7 months (ranging from 3 to 12 months). New fractures: We are uncertain whether Chinese herbal medicines reduce the chance of having a new bone fracture. Seven trials evaluated the incidence of fractures. However, these trials were small and had flaws in their methods. Quality of life: People who took Bushenhuoxue therapy plus calcium carbonate tablets and alfacalcidol rated their quality of life to be 5.30 points better on a scale of 0 to 100 after three months compared to people who did not take the herbal medicine. People who took Bushenhuoxue therapy plus calcium carbonate tablets and alfacalcidol rated their quality of life to be 56.05 on a scale of 0 to 100. People who took calcium carbonate tablets and alfacalcidol rated their quality of life to be 50.75 on a scale of 0 to 100. Serious side effects or deaths: No serious side effects or deaths occurred in the trials. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects may include a mild stomach ache or diarrhoea. Bone mineral density (the amount and type of minerals in the bone): We found studies that compared Chinese herbal medicines with placebo (fake treatment), with no treatment and with conventional medicine. We also found studies that compared Chinese herbal medicines plus conventional medication with just conventional medication. Compared to placebo (fake treatment), three studies showed that bone mineral density increased slightly with Chinese herbal medicines. Compared to no treatment or conventional medicine, some studies showed an increase in bone mineral density with Chinese herbal medicines while others did not. When Chinese herbal medicines plus conventional medication was compared with just conventional medicine, some studies showed an increase in bone mineral density while others did not. In people with osteoporosis: - Chinese herbal medicines may improve bone mineral density and quality of life slightly. Further research is likely to change this estimate of how Chinese herbal medicines affect bone mineral density and quality of life. - We are uncertain whether Chinese herbal medicines reduce the chance of having a new bone fracture. - No trial reported death or serious side effects.
We identified nine studies that compared NOACs with warfarin, four of which were ongoing studies. We included five trials involving 8373 participants in this review. Evidence is current to February 2019. There may be little or no difference in effect between NOACs and warfarin in people with atrial fibrillation, who underwent heart vessel stenting. However, NOACs probably reduce the need for hospitalisation compared to warfarin. NOACs may be safer than warfarin. One of NOACs drugs (dabigatran) may reduce the rate of both major and non-major bleeding. Other NOAC drugs (apixaban and rivaroxaban) probably reduce the rate of non-major bleeding. There was no significant difference between NOACs agents in any primary or secondary outcomes. The evidence ranged from Very low- to moderate-certainty, indicating the need for more research on this issue.
We found 56 trials (involving a total of 3781 women, all with stress urinary incontinence but some with urgency urinary incontinence as well) comparing electrical stimulation to no treatment or to any other available treatment. For cure or improvement of SUI, electrical stimulation was probably better than no active or sham treatment. There was not enough evidence to say whether it was any better than pelvic floor muscle training for curing or improving SUI, or for quality of life. Adding electrical stimulation to pelvic floor muscle training may not make much difference to cure or improvement of SUI. It is uncertain whether it offers any improvement in quality of life compared with pelvic floor muscle training. We found that few women reported adverse effects with electrical stimulation, but there was not enough reliable evidence comparing electrical stimulation to other treatments to know more about its safety. There was not enough evidence comparing electrical stimulation to other existing treatments such as drug therapy, pelvic floor muscle training plus vaginal cones, surgery, or different forms of electrical stimulation, to provide evidence-based guidance on which would be better, and for which women, in curing or improving SUI or in improving quality of life. There was no information from these studies to judge value for money. There is some evidence to support the use of electrical stimulation for stress urinary incontinence in women, but we are still very uncertain about the full potential of this treatment because of the low quality of the existing evidence. While we found evidence indicating that electrical stimulation may be better than no treatment, we did not find enough well-designed trials with enough women to fully answer our review questions, so we do not yet know if ES is better or worse than other treatments.
This review is up-to-date as of 8 April 2019. The review includes 44 studies involving 1809 people who were 17 to 77 years old. The review compared an intervention with another intervention, a placebo or a control. It looked at eight different ways to control bad breath: mechanical cleaning (e.g. tongue cleaners and toothbrushes), chewing gums, systemic deodorising agents (e.g. mushroom extract that you eat), topical agents (e.g. gel that you apply), toothpastes, mouthrinse/mouthwash, tablets, and combination of different treatments. The evidence was very uncertain for mechanical tongue cleaning versus no tongue cleaning, 0.6% eucalyptus chewing gum versus placebo chewing gum, 1000 mg mushroom extract versus placebo, hinokitiol gel versus placebo gel, 0.3% triclosan toothpaste versus control toothpaste, mouthwash containing chlorhexidine and zinc acetate versus placebo mouthwash, and brushing plus cetylpyridium mouthwash versus brushing. Harmful effects of the different interventions were not reported or were not important. The level of certainty we have in these findings is low to very low. This was due mainly to risk of bias and the small number of people studied in the included trials. We do not have enough evidence to say which intervention works better to control bad breath.
We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of vitamin C supplementation in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes). The evidence is current to May 2016. Eight trials fulfilled our inclusion criteria. One large trial looked at the effects of vitamin C supplements on the risk of major CVD events (fatal and non-fatal) and found no beneficial effects. This trial was however conducted in middle-aged and older male doctors in the USA and so its not certain that the effects are the same in other groups of people. Seven trials looked at the effects of vitamin C supplements on CVD risk factors. We could not combine these trials as there was lots of missing information and differences between the trials in terms of the participants recruited, the dose of vitamin C and the duration of trials. Overall, there were inconsistent effects of vitamin C supplements on lipid levels and blood pressure and more research is needed. Four of the included studies did not mention sources of funding of the study, two had non-commercial (grants) funding and two had both commercial (industries) and non-commercial funding (grants). The evidence was of low or very low quality for major CVD events (myocardial infraction, stroke, angina and coronary artery bypass grafting), all-cause mortality and CVD mortality. The evidence was of low quality because it was not applicable to the general population (included only USA male physicians) and limited studies of vitamin C on the prevention of CVD.
A lay health worker is a member of the community who has received some training to promote health or to carry out some healthcare services, but is not a healthcare professional. In the studies in this review, lay health workers carried out different tasks. These included giving help and advice about issues such as child health, child illnesses, and medicine taking. In some studies, lay health workers also treated people for particular health problems. The studies took place in different settings. In many of the studies, lay health workers worked among people on low incomes in wealthy countries, or among people living in poor countries. What the research says The use of lay health workers, compared to usual healthcare services: - probably leads to an increase in the number of women who start to breastfeed their child; who breastfeed their child at all; and who feed their child with breastmilk only; - probably leads to an increase in the number of children who have their immunization schedule up to date; - may lead to slightly fewer children who suffer from fever, diarrhoea and pneumonia; - may lead to fewer deaths among children under five; - may increase the number of parents who seek help for their sick child.  The use of lay health workers, compared to people helping themselves or going to a clinic: - probably leads to an increase in the number of people with tuberculosis who are cured; - probably makes little or no difference in the number of people who complete preventive treatment for tuberculosis.
For this updated review, we looked at the evidence from 11 randomised controlled clinical trials comparing phenytoin and carbamazepine, based on how effective the drugs were at controlling seizures (i.e. whether people went back to having seizures or had long periods of freedom from seizures (remission)), and how tolerable any related side effects of the drugs were. Methods We were able to combine data for 595 people from four of the 11 trials; for the remaining 507 people from seven trials, information was not available to use in this review. The evidence is current to August 2018. Key results This review of trials found no difference between these two drugs for the seizure types studied for the outcomes of treatment failure (withdrawal from treatment for any reason and also withdrawal from treatment due to continuing seizures or due to side effects) and controlling seizures (recurrence of seizures or achievement of a seizure-free period (remission) of six months or 12 months). Three-quarters of the people recruited in the four trials had focal onset seizures and only one quarter of the people recruited in the four trials had generalised onset seizures, so the results of this review mainly apply to people with focal onset seizures and the results are very limited for people with generalised onset seizures. More information is needed for people with generalised onset seizures. Some side effects reported by people taking carbamazepine and people taking phenytoin were abdominal pain, nausea, vomiting, tiredness, motor problems (such as poor co-ordination), cognitive problems (poor memory), rashes and other skin problems. Certainty of the evidence We judged the certainty of the evidence as moderate to low for the evidence of treatment failure, moderate for remission outcomes and low for seizure outcomes, as it is likely that misclassification of seizure type influenced the results of the review. Within two of the trials providing data for this review, the design of the trial meant that the people and treating clinicians knew which medication they were taking. This design may have influenced the results. Some of the trials contributing data to the review had methodological problems, which may have introduced bias and inconsistent results into this review, and some individuals over the age of 30 with newly-diagnosed generalised onset seizures may have had their seizure type wrongly diagnosed. These problems may have affected the results of this review and we judged the certainty of the evidence provided by this review as moderate for people with focal onset seizures and of low certainty for people with generalised onset seizures. We do not suggest using the results of this review alone for making a choice between carbamazepine or phenytoin for the treatment of epilepsy. We suggest that all future trials comparing these drugs or any other antiepileptic drugs should be designed using high-quality methods, and that the seizure types of people included in trials should be classified very carefully to ensure results are also of high quality.
We found 14 studies with a total of 30 publications with 675 participants. Most of the studies (8) had fewer than 50 participants and lasted less than 12 months. None of these studies compared the quality of life of participants with regard to different treatments. Also, no study compared a particular therapy to a "wait and see" strategy. Most of the studies described adverse effects, from mild symptoms to severe life-threatening or even lethal complications depending upon the type of treatment. More aggressive treatment options like systemic chemotherapy showed more adverse effects than topical therapies that are applied directly to the skin. None of the trials reported a long-term benefit (i.e. clearance of all symptoms of disease lasting at least two years). Therefore, the conclusions from these studies should be treated with caution. Treatment of mycosis fungoides should be based on the stage of progression of the disease with a focus on the limitations of severe adverse effects. There is a great need for extensive and well planned research to find effective ways to manage this disease and to evaluate treatment strategies that might be curative. People with mycosis fungoides are encouraged to participate in such trials.
The review of trials of selenium supplementation for preterm babies found that it reduces sepsis (blood infection). It has not been shown to reduce other complications or increase survival. No adverse effects were reported. Higher than usual levels of selenium supplementation may be beneficial, but more research is needed as most of the evidence comes from a country where selenium levels were unusually low.
We identified eight studies investigating this therapy in 232 infants. Although we deemed the risk of bias as low, very few studies reported our outcomes of interest. The included trials did not show a beneficial effect of inhalation corticosteroids on death or BPD. In addition, the safety of inhalation corticosteroids was assessed in only a small number of trials. Based on these results, inhalation corticosteroids initiated after the first week of life cannot be recommended for preterm infants at risk of BPD. More studies are needed. The quality of the evidence was low to very low for the main outcomes.
In this review, 14 double-blind, placebo controlled randomised clinical trials (RCTs) were found. They did not all measure the same outcomes and several did not explain what other heart failure treatments patients were receiving. Those trials that could be included in a meta-analysis showed improvements in heart failure symptoms and in the function of the heart. The results, therefore, are suggestive of a benefit from hawthorn extract used in addition to conventional treatments for chronic heart failure.
In October 2017, we identified two relevant studies comparing oral plus inhaled dual therapy versus oral therapy alone. They included a total of 118 adults with an average age of 62.8 years. One study compared inhaled tobramycin plus oral ciprofloxacin with oral ciprofloxacin, and the second study compared inhaled gentamicin plus a systemic (affecting the whole body, rather than just the lungs) antibiotic with a systemic antibiotic alone. Only a research summary was available for the latter. Published papers did not report study funding sources Results from one small trial of 53 adults show no evidence of treatment benefit with oral plus inhaled dual therapy in terms of successful treatment of exacerbations, the occurrence of serious unwanted events, amount of phlegm, lung function, or resistance to antibiotic treatment. However, we found insufficient evidence to permit confident conclusions about their use. The overall quality of the evidence was very poor, largely because one of the studies was not well described and included few participants. Information on exacerbations, exercise ability, and quality of life was not reported. We did not identify any trials that compared other types of dual antibiotic therapy, and we found none that included children. Therefore uncertainty remains concerning the use of dual antibiotics, and further high-quality studies are needed to examine the role of dual antibiotics in the treatment of adults and children with bronchiectasis.
We included 21 trials in which a total of 1400 participants with intermittent claudication (65% male, mean age 66 years) had been assigned to supervised exercise therapy, home-based exercise therapy, or walking advice (search last run December 2016). The overall methodological quality of included trials was moderate to good. However, some trials had enrolled only small numbers of participants. Trials lasted from six weeks to two years. This review shows that patients participating in a supervised exercise program improve their walking ability to a greater extent than those completing a home-based exercise program or just following walking advice. After three months, the maximal walking distance for participants following the supervised exercise program was 120 or 210 meters farther than the maximal walking distance for those who followed a home-based exercise program or received walking advice, respectively. To put these increases in context, a US football field is roughly 90 meters (or 100 yards) long. Before participating in the exercise program, the maximal walking distance of participants was 290 meters with a pain-free walking distance of 140 meters, so this improvement is likely to have a positive impact on their lives. Results of the home-based exercise program were similar to those reported for walking advice. Compared with home-based exercise therapy, supervised exercise therapy was more beneficial for pain-free walking distance but had no effect on quality of life measures nor on self-reported functional impairment. Compared with walking advice, supervised exercise therapy was more beneficial for pain-free walking distance and self-reported functional impairment, as well as for some quality of life measures (e.g., physical functioning, pain, and physical component summary after 12 months), and home-based exercise therapy had no effect. Data show no obvious effects on mortality rates. Thirteen of the 1400 participants died, but no deaths were related to exercise therapy. Overall, adherence to supervised exercise therapy was approximately 80%, which was similar to that reported with home-based exercise therapy. Only limited adherence data were available for walking advice groups. Evidence of moderate and high quality shows that supervised exercise therapy improves walking distance (maximal and pain-free) to a greater extent than home-based exercise therapy and walking advice, respectively. Trials show no clear differences in quality of life measures nor in self-reported functional impairment between supervised exercise therapy and home-based exercise therapy. However, evidence is of low and very low quality, respectively. Investigators detected some improvements in quality of life favoring supervised exercise therapy over walking advice, but analyses were limited by small numbers of studies and participants. More research is needed on disease-specific quality of life and other functional outcomes, such as walking behavior and physical activity, as well as on long-term follow-up. Adhering to an exercise program is important because it leads to decreased leg pain and improved quality of life, as well as to likely improvement in general physical condition.
In this review we aimed to assess if medications used in the management of SIB in adults with intellectual disability are safe and help reduce the behaviours. We looked for studies that compared antidepressants, antipsychotics or mood stabilisers with no active medication (placebo). We found only five studies: four examined the effects of naltrexone, an opioid antagonist (which works through modulating pain perception) and one examined the antidepressant clomipramine. There were only a total of 50 participants included in these studies, which was not enough to determine whether or not the intervention resulted in any improvement. Three of the naltrexone studies and the one clomipramine study indicated the drugs resulted in clinical improvement in SIB, but more evidence is needed. The data is too limited for us to be able to draw any firm conclusions about the benefits or safety of any medications for SIB in this population. We need more studies where many more participants are involved to know whether medications help in reducing SIB and if they are safe.
We searched the literature until 15 September 2013. We included all adults who underwent elective major abdominal surgery. We included only studies in which the intervention was started postoperatively. We employed the standard methods of the Cochrane Anaesthesia Review Group for data collection and analysis. A total of 709 participants were included in the 10 selected trials. Considerable differences between studies were noted in the populations studied, duration of treatment and supportive care provided. Two controlled trials (413 participants) reported deaths; no clear evidence showed a difference between CPAP and control groups. Six trials (249 participants) reported on atelectasis, which was reduced in the CPAP group. Pneumonia was reported in five trials (563 participants), and the rate of pneumonia was reduced in the CPAP group. The need for further respiratory support with artificial ventilation (reintubation) was reported in two studies, which favoured CPAP. No clear evidence revealed a difference between CPAP and control groups in rates of admission to intensive care units, nor were severely low oxygen levels reported. Few studies reported on length of hospital stay and harm due to CPAP. Substantial variability was seen in trial characteristics (heterogeneity), and risk of bias was high in six of the 10 studies. The included studies were small, and some were at least 20 years old; currently, computed tomography (CT) scans are used more often than chest x-rays and clinical examination alone for diagnosis. The summary of findings (GRADE) suggests that the strength of evidence supporting the use of CPAP was ‘very low.’ This means that recommendations based on currently available evidence from randomized controlled trials investigating use of CPAP during the postoperative period are not definitive.
Nine studies met the inclusion criteria for the review. These studies were added to the six that we found the last time we updated the review, bringing the total to 15 studies. Seven of these studies reported positive outcomes for healthcare processes or patient outcomes, or both, four studies reported mixed outcomes (positive and neutral) and four reported no effects of IPE. The studies differed in many respects. They were conducted in different areas of clinical practice and included different IPE interventions. The study designs and outcome measures were also different. All 15 studies compared outcomes following an IPE intervention to outcomes, either in similar clinical settings that did not receive the IPE intervention, or in the same clinical setting before the intervention was made. Because no studies compared an interprofessional intervention to a profession-specific intervention, our understanding of interprofessional interventions is limited. The small number of studies included in this review, and their varied nature, limit our understanding of the key components of IPE and its effectiveness. More studies are needed to allow sound conclusions to be reached about the effectiveness of IPE, as well as to inform IPE policy development. In particular, these should include: first, studies that assess the effectiveness of IPE interventions compared to separate, profession-specific interventions; second, RCT, CBA or ITS studies with qualitative strands examining processes relating to the IPE and practice changes; third, cost-benefit analyses.
No trials with clinically-important outcomes were identified. Many of the studies were conducted in convenience samples of patients. Many of the trials were methodologically flawed. Adverse events were rarely reported. Decrease in serum potassium was the most frequently reported outcome: for this outcome beta agonists and intravenous insulin-and-glucose were effective. The combination may be more effective than either alone.
One unpublished trial met our inclusion criteria. This randomised 34 patients with chronic frontal sinusitis into two groups: in one group balloon dilation was used to open up the drainage pathways of the frontal sinuses; in the other group conventional endoscopic sinus surgery was used to do the same. For both groups all other sinuses were treated using conventional functional endoscopic sinus surgery. Balloon dilation did not show an improvement in the resolution of frontal sinusitis as demonstrated by imaging studies, however the technique was associated with an increased likelihood that someone observing a frontal sinus opening would find this open. However, it is not clear whether this was a statistically significant result. The study report appeared to be biased in the way it reported its outcome measures. At present, therefore, we cannot recommend the use of balloon dilation of sinus ostia over conventional surgical treatment modalities in this setting.
The review of 17 trials found that these training programs help health professionals to identify smokers and increase the number of people who quit smoking. The programs also increase the number of people offered advice and support for quitting by health professionals.
The researchers searched medical databases up to September 2014, and identified 22 studies with a total of 7436 participants that were relevant to the research question. The studies investigated the following comparisons: - nine studies compared sterile gauze with standard polyurethane dressings; - six studies compared standard polyurethane dressings with chlorhexidine gluconate-impregnated dressings (chlorhexidine gluconate is an antibacterial disinfectant); - one study compared standard polyurethane dressings with silver-impregnated dressings (silver compounds may have antibacterial properties); - one study compared standard polyurethane dressings with hydrocolloid dressings; - one study compared 'modern' gas permeable standard polyurethane dressings with 'old' (original) standard polyurethane dressings; - one study compared highly adhesive transparent standard polyurethane dressings with chlorhexidine gluconate dressings; - one study compared standard polyurethane dressings with sutureless (stitchless) securement devices; - one study compared sterile gauze with no dressing; and - one study compared chlorhexidine gluconate dressings with no dressings. The included studies sometimes did not clearly report the methods they had used to minimise accidental or statistical error, but overall the methods were adequate. Analysis of the study results showed that there is high quality evidence that securing a CVC with a dressing impregnated with a medication (chlorhexidine gluconate-impregnated or silver) reduces catheter-related blood stream infection compared with a dressing without medication. The results indicated moderate quality evidence for a reduction in the frequency of catheter-related BSI per 1000 patient days (this is a unit used in research that represents patient use; in this case 1000 patient days is equal to 1000 patients using CVCs for one day, or 500 patients using CVCs for two days, or 250 patients using CVCs for four days, etc.) when a chlorhexidine gluconate-impregnated dressing was used rather than a standard polyurethane dressing. When the risk of infection with chlorhexidine gluconate-impregnated dressings was compared with the risk with standard polyurethane dressings in another way (by calculating the ratio of the risk of infection with one versus the other without taking account to patient days of use) this difference was less clear. A less direct measure of infection, that is the extent of bacterial colonisation of the tip of the catheter after removal, showed more bacteria with the standard polyurethane dressing (moderate quality evidence). The studies that contributed to this research were mainly carried out in intensive care unit settings, where a large number of CVCs are used for short durations. Other types of dressings and securement products for CVCs that were investigated by the studies analysed here did not show any observable effects on catheter-related BSI, catheter tip colonisation or any of the other outcomes assessed, such as skin irritation, failed catheter securement, condition of the dressing and patient death. More, high quality research is needed to investigate the relative effects of the wide range of dressing and securement products that are available for CVCs. This plain language summary is up-to-date as of 5th June, 2015.
We included randomised controlled trials that compared routine invasive strategies to conservative strategies in patients with UA and NSTEMI in the stent era. We searched the available literature up to 25 August 2015. We included eight studies with 8915 participants: five trials were in the review version published in 2010, and three were new trials. Of the included participants with UA and NSTEMI, there were 4545 in the invasive strategy arm and 4370 in the conservative strategy arm. Evidence failed to show appreciable risk reduction in all-cause mortality and death or non-fatal myocardial infarction (MI) with routine invasive management strategy compared to conservative strategies. There was appreciable risk reduction in MI, refractory angina and re-hospitalisation with routine invasive strategies compared to conservative strategies, but this was associated with an increased risk of procedure-related MI and bleeding complications. The quality of the evidence in this review update ranged from low quality to moderate quality. Low quality evidence was as a result of serious risk of bias and uncertainty surrounding the effect, while moderate quality evidence was only due to serious risk of bias. The debate continues as to which strategy is better. The invasive strategy reduces the incidence of further chest pain or re-hospitalisation. Also, long-term follow-up from three studies suggests that it lowers the risk of a heart attack over the next three to five years. However, the invasive strategy also is associated with double the risk of heart attack during or soon after initial treatment, as well as an increased risk of bleeding. In summary, the published scientific research suggests that the invasive strategy may have particular benefit in those patients who are at high risk for recurrent events, and that patients at low risk for a recurrent event may even suffer harm from such an approach.
We ran electronic searches of Cochrane Schizophrenia's trial register, most recently on 24 January 2019, for trials that randomised people with schizophrenia and are stable on haloperidol treatment to either discontinue taking haloperidol or to continue taking haloperidol. The review authors found and checked 54 records. Five trials met the review requirements and provided usable data. The evidence currently available from randomised controlled trials is of very low quality and suggests that haloperidol discontinuation is associated with poorer outcomes for people with schizophrenia in terms of their overall symptom improvement (global state). It also shows that people discontinuing haloperidol treatment are more likely to experience relapse (reoccurrence of symptoms) during the first year post treatment. There were no trials providing evidence on what happens after the first year. The number of participants leaving the study early (which can be an indication of satisfaction with treatment) was similar between the two treatments. The very low quality of the currently available evidence is due to methodological shortcomings of the included trials. This lowers our confidence in the reliability of results, and hampers their generalisability to real-world situations. It is disappointing that only a small number of studies were identified, and the size and quality of these studies were limited. The evidence available does not enable us to fully answer important questions regarding the effects of discontinuing haloperidol treatment. In particular there is no evidence available related to the side effects of haloperidol. New trials of better quality are needed.
We included randomized controlled trials involving adults undergoing any type of cardiac surgery under general anaesthesia with or without cardiopulmonary bypass where researchers compared epidural pain relief around the time of surgery against other forms of pain relief. Surgeries performed were coronary artery bypass grafting or valvular procedures and surgeries for congenital heart disease. The average age of participants was between 43 and 75 years. Outcomes were measured up to one year after surgery. We included 69 studies with 4860 participants. Where stated, the studies were funded by governmental resources (five studies), charity (eight), institutional resources (23), or in part by the industry (two). In all, 31 trials did not mention the source of funding. The evidence is current to November 2018. When researchers compared epidural analgesia versus systemic pain relief (e.g. by an analgesic given directly into a vein), they could not detect any difference in the number of deaths in the first 30 days after surgery (38 studies, 3418 participants). There might be a difference in the number of people experiencing heart attacks (26 studies, 2713 participants). These findings were supported by low-quality evidence. We found a small reduction in the risk of respiratory depression with epidural pain relief (21 studies, 1736 participants), but not in the risk of pneumonia (10 studies, 1107 participants) (low- or moderate-quality evidence). The reduced risk of respiratory depression was more obvious when cardiopulmonary bypass was needed for cardiac surgery. Epidural analgesia reduced the risk of atrial fibrillation or atrial flutter early in recovery at zero to two weeks (18 studies, 2431 participants; moderate-quality evidence). The number of cerebrovascular accidents was not clearly different (18 studies, 2232 participants), and no lasting neurological complications or epidural haematomas were reported (53 studies, 3982 participants; very low- or low-quality evidence). Although epidural analgesia may have reduced the duration of tracheal intubation, this was noted mainly in older studies, and clinical practices have changed since that time (40 trials, 3353 participants; moderate-quality evidence). We found only six studies that compared epidural pain relief versus application of local anaesthetic on the body surface to produce peripheral nerve blocks directly into the space around the lungs (intrapleural analgesia) and onto the surgical wound (wound infiltration). These studies provided low- or very low-quality evidence and did not report on many of the outcomes for this review. Study authors reported no heart attacks and no epidural haematomas. We rated the quality of evidence as moderate, low, or very low. We included too few participants in our review to rule out any differences in the number of patient deaths between epidural analgesia and systemic analgesia, nor to see any increase in epidural haematomas.
The review of trials found that radiant warmers increase water loss in low birthweight babies in the newborn period when compared to incubators and that this water loss needs to be taken into account when daily fluid requirements are calculated. However, there was not enough information available for this review to enable assessment of other important effects of radiant warmers. Therefore, at the present time, it is not clear which method of maintaining body temperature is best for newborn babies - radiant warmers or incubators. More research is necessary.
Poor housing is associated with poor health. This suggests that improving housing conditions might lead to improved health for residents. This review searched widely for studies from anywhere in the world which had investigated whether or not investment to improve housing conditions is linked with improvement in health. A huge amount of research on housing and health has been published but very few studies have investigated if improved housing conditions impact on residents' health. Neighbourhood renewal programmes often include housing improvements but a key aim of these programmes is to improve the area by attracting new residents, often those who are better off. In these programmes, improvements in health statistics may simply reflect a change in the population living in an area and the original population may not have benefited from the improved living conditions. This review only looked at studies where changes in health for the original population were being investigated rather than changes for the area. We identified 39 studies which assessed changes in health following housing improvement. The studies covered a wide range of housing improvements. The housing improvements in high income countries, and conducted in the past 30 years, included refurbishment, rehousing, relocation, installation of central heating and insulation. Studies from the developing world included provision of latrines. Older studies (pre-1965) examined changes in health following rehousing from slums. Overall, it would appear that improvements to housing conditions can lead to improvements in health. Improved health is most likely when the housing improvements are targeted at those with poor health and inadequate housing conditions, in particular inadequate warmth. Area based housing improvement programmes, for example programmes of housing-led neighbourhood renewal, which improve housing regardless of individual need may not lead to clear improvements in housing conditions for all the houses in a neighbourhood. This may explain why health improvements following these programmes are not always obvious. Improvements in warmth and affordable warmth may be an important reason for improved health. Improved health may also lead to reduced absences from school or work. Improvements in energy efficiency and provision of affordable warmth may allow householders to heat more rooms in the house and increase the amount of usable space in the home. Greater usable living space may lead to more use of the home, allow increased levels of privacy, and help with relationships within the home. An overview of the best available research evidence suggests that housing which promotes good health needs to be an appropriate size to meet household needs, and be affordable to maintain a comfortable indoor temperature.
We included 36 randomised controlled trials with 2706 participants, examining the effect of anti-inflammatory treatments on seborrhoeic dermatitis. These trials were short-term; most of them lasting four weeks or less. Topical steroid treatment (such as hydrocortisone and betamethasone), topical calcineurin inhibitor treatment (such as tacrolimus and pimecrolimus), and topical lithium salts all reduced the symptoms of seborrhoeic dermatitis when compared with placebo treatment. Mild (such as hydrocortisone 1%) and strong (such as betamethasone) steroid compounds were comparable in short-term follow up. Short-term total clearance was achieved with antifungal azole treatment (such as ketoconazole and miconazole), as well as with steroids. Strong steroids were better than azole treatment in reducing erythema, scaling, and pruritus, and were comparable in terms of safety. Steroids were also as effective as calcineurin inhibitors, but side-effects occurred more often with calcineurin inhibitors. We found no differences between calcineurin inhibitors and azole treatments in effectiveness or side-effects. Lithium was more effective than azoles but had a similar frequency of side-effects (one study). The most common side-effects were burning, itching, erythema, and dryness in all treatment groups. Topical anti-inflammatory agents are useful in treating seborrhoeic dermatitis. Steroids are the most investigated anti-inflammatories. We still do not know the effects and safety of topical anti-inflammatory treatments in long-term or continuous use. This is regrettable as the disease is chronic in nature. Furthermore, there are no data concerning the effects of different treatments on quality of life.
The review authors found 16 relevant studies. Twelve of the studies were from the USA. The other studies were one each from Australia, Sweden, Tanzania, and the UK. These studies showed the following. When adolescents (girl or boys, or both) and their parents were given vaccination information and education, more adolescents got HPV vaccines (high-certainty evidence). When adolescents were given gift vouchers, more adolescents may have got HPV vaccines (low-quality evidence). However, we were uncertain whether giving adolescents and their parents health education, cash, and gift packages led to more adolescents getting hepatitis B vaccines (very low certainty evidence). When laws were passed stating that adolescents must be vaccinated to go to school, substantially more adolescents probably got hepatitis B vaccines (moderate-certainty evidence). When healthcare providers were reminded to vaccinate adolescents when they opened their electronic medical charts, this probably had little or no effect on the number of adolescents who got tetanus–diphtheria–pertussis, meningococcal, HPV, or influenza vaccines (moderate-certainty evidence). When healthcare providers were given education with performance feedback, more adolescents may have got HPV vaccines (low-certainty evidence). When healthcare providers were given education, individualised feedback, frequent visits, and incentives, more adolescents probably got HPV vaccines (moderate-certainty evidence). When healthcare providers and parents were targeted in several ways, including through education, telephone calls, and radio messages, more adolescents may have got HPV vaccines (low-certainty evidence). These studies compared the use of these approaches (health education, gifts and rewards, laws, or reminders) to using no approaches. In addition, one study from Tanzania gave vaccination information to all girls that were in school class six but were not necessarily of the same age. They were compared to girls who were given vaccination information because they were all born in the same year, but were not necessarily in the same class. This study showed that the class-based approach probably led to slightly more girls getting HPV vaccines (moderate-certainty evidence). How up-to-date is this review? The review authors searched for studies that had been published up to 31 October 2018.
The search for trials took place in January 2014. This review of 75 randomised controlled trials (13,793 women) found that oral misoprostol appears to be at least as effective as current methods of induction. Nine trials (1,282 women) showed that oral misoprostol was equivalent to intravenous infusion of oxytocin. There were no obvious differences in the number of women who had a vaginal birth within 24 hours, or the number of women who experienced uterine hyperstimulation with changes to the baby's heart rate, although there were fewer caesarean sections in the group of women who were given oral misoprostol. For the 37 thirty seven trials (6,417 women) that compared oral and vaginal misoprostol, there was little difference in the number of women who had a vaginal birth within 24 hours, uterine hyperstimulation with changes to the baby's heart rate, or caesarean section. In 10 trials (3,240 women) comparing oral misoprostol with a vaginal prostaglandin (dinoprost), there was little difference in the frequency of vaginal birth within 24 hours, uterine hyperstimulation with changes to the baby's heart rate, or caesarean section. The nine trials that compared oral misoprostol with placebo (1,109 women) and found that oral misoprostol is more effective than placebo for inducing labour. Women in the oral misoprostol group were more likely to have vaginal birth within 24 hours, and less likely to have a caesarean section. There was little difference between groups in terms of the number of women who experienced uterine hyperstimulation with changes to the baby's heart rate. Five trials compared oral misoprostol with intracervical (inserted into the entrance of the womb) prostaglandin E2 (681 women). Oral misoprostol was associated with fewer instances of failure to achieve vaginal birth within 24 hours but more frequent uterine hyperstimulation with changes to the baby's heart rate. The available data for this comparison was limited and the differences in caesarean birth were small. Overall, the incidence of serious illness or death of the mother or her baby was rare and no meaningful results were available for any of the comparisons in this review. Using oral misoprostol to induce labour is effective at achieving vaginal birth. It is more effective than placebo, as effective as vaginal misoprostol and vaginal dinoprostone, and results in fewer caesarean sections than using oxytocin alone. In some countries where misoprostol is not licenced for the purpose of inducing labour, many clinicians may prefer to use some other licensed product such as dinoprostone. Where oral misoprostol is used, evidence suggests that an appropriate dose may be 20 to 25 mcg in solution. Given that safety is the primary concern, the evidence supports the use of oral regimens over vaginal regimens. This is particularly important in settings where the mother is at a higher risk of infection and where there may be insufficient staff to closely monitor the mother and her baby.
Psychological therapies have been proposed for the treatment of pathological and problem gambling, and this review summarised current evidence for these therapies. It included best-quality randomised trials, where therapy was compared with conditions including 'no treatment’ controls or referral to Gamblers Anonymous. It considered categories of therapy including: (1) cognitive-behaviour therapy (CBT); (2) motivational interviewing therapy; (3) integrative therapy; and (4) other psychological therapy. The search identified 14 studies and we combined data from these. Data from nine studies indicated benefits of CBT in the period immediately following treatment. However, there were few studies across longer periods of time (e.g. 12 months) after treatment, and little is known about whether effects of CBT are lasting. Data from three studies of motivational interviewing therapy suggested some benefits in terms of reduced gambling behaviour, but not necessarily other symptoms of pathological and problem gambling. However, the data come from few studies and conclusions regarding motivational interviewing therapy require further research. There were also few studies that provided evidence on integrative therapies (two studies) and other psychological therapies (one study), and there is currently insufficient data to evaluate the efficacy of these therapies
From a search of the literature in January 2016, we identified six randomised controlled trials that involved 2452 participants aged between 48 and 65 years to be analysed. We found that homocysteine-lowering therapies had no benefits for heart health in people with advanced kidney disease who were on dialysis. These therapies did not achieve any reduction in rates of heart disease-related death. However, homocysteine-lowering therapies were generally well tolerated, and had a mild side effect profile. Overall, studies were assessed as high quality.
The aim of this review was to evaluate the effects of haloperidol for schizophrenia and other similar serious mental illnesses compared with ‘dummy’ or no treatment (placebo). A new search for trials was carried out in May 2012 and the review now includes 25 studies with a total of 4651 people. Review authors rated the quality of evidence reported in the trials for seven main outcomes (global state, death, discharge from hospital, relapse, leaving the study early, adverse effects and satisfaction with treatment). For global state, leaving the study early and adverse effects the reviewers rated the evidence as moderate quality, however, relapse and discharge from hospital were rated to be very low quality evidence. There were no data available for death and satisfaction with treatment. Based on moderate quality evidence, haloperidol was found to be better than placebo in treating schizophrenia. More people given haloperidol improved in the first six weeks of treatment than those given placebo. However, a significant number of people on haloperidol suffered from side effects, including muscle stiffness, uncontrollable shaking, tremors, sleepiness and restlessness. Authors concluded that haloperidol is a potent and effective antipsychotic for treating the symptoms of schizophrenia but has the potential to cause debilitating side effects. People with schizophrenia and psychiatrists may wish to prescribe a newer antipsychotic drug with fewer side effects. Finally, a large proportion of other information and data in the trials were poor and badly reported, meaning that better studies are required. Many people, from both groups left the trials early. This suggests that the design and running of the trials was poor and perhaps not acceptable to people. In light of these findings, it is perhaps surprising that haloperidol is a benchmark antipsychotic in widespread use for treating schizophrenia. It is also surprising that haloperidol is widely used as a comparison for new medication. Haloperidol is an effective antipsychotic drug but has serious and debilitating side effects. Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness.
In this review, four randomized trials that compared the use of ECMO to the conventional approach to supporting these infants with severe breathing problems were identified. Overall, these trials showed a strong benefit for ECMO regarding survival at the time of hospital discharge. This is particularly true for infants without a specific problem of lung formation (congenital diaphragmatic hernia). The result implies that for every three babies with breathing problems and lung failure who were treated with ECMO rather than conventional ventilation, one more infant will survive. Although little information is available regarding long-term follow-up, one trial in the United Kingdom shows both benefits of ECMO and cost-effectiveness of the use of ECMO.
Data from six of the studies were combined in the analysis. All the participants (including adults and children) were previously taking at least one antiepileptic medicine and all were continuing to have seizures. Either gabapentin (an antiepileptic medicine) or a placebo (a tablet that contains no medicine) was added to the medicine regimen. The results showed that gabapentin effectively reduced seizures when used as an additional treatment. Compared to a placebo, gabapentin was almost twice as likely to reduce seizures by 50% or more. The most common side effects associated with gabapentin ware ataxia (poor co-ordination and unsteady gait), dizziness, fatigue and drowsiness. Overall the quality of evidence was low to moderate as information was not reported for all participants in some of the trials and some of the results were imprecise. Research is needed into the effects of the long-term use of gabapentin. The evidence is current to 20 March 2018.
The review authors searched the medical literature and found evidence that providing a psychosocial treatment in addition to pharmacological detoxification treatment to adults who are dependent on heroin use is effective in facilitating opioid detoxification. This conclusion is based on eleven controlled studies involving 1592 adults. The addition of a psychosocial treatment to substitution detoxification treatment improved the number of people who completed treatment (relative risk (RR) 1.47), reduced the use of opiate (RR 0.82), increased abstinence from opiate at follow up (RR 2.43) and halved the number of failures to attend clinic absences (RR 0.48). The findings of an improved rate of clinical attendance may help in suppressing illicit drug use and provides clinical staff with more opportunities to counsel patients in psychiatric, employment and other drug and non-drug related areas. Variations in the populations who are substance users and use of a wide range of different psychosocial interventions means that it is difficult to single out particular therapeutic interventions.
We found 36 randomized controlled trials comparing rLH combined with rFSH versus rFSH alone among 8125 women undergoing IVF/ICSI. This is an update of a previous Cochrane Review, first published in 2007. The evidence is current to June 2016. Only seven of the 36 studies clearly stated that they were funded by government or research institutes. Six were funded by pharmaceutical companies and the rest did not state their source of funding. We found no clear evidence of a difference between rLH combined with rFSH and rFSH alone in rates of live birth or OHSS. The evidence for these comparisons was of very low-quality for live birth and low quality for OHSS. We found moderate quality evidence that the use of rLH combined with rFSH may lead to more ongoing pregnancies than rFSH alone. There was also moderate-quality evidence suggesting little or no difference between the groups in rates of miscarriage. There was no clear evidence of a difference between the groups in rates of cancellation due to low response or imminent OHSS, but the evidence for these outcomes was of low or very low quality. We conclude that the evidence is too limited to encourage or discourage stimulation regimens that include rLH combined with rFSH in IVF/ICSI cycles. The quality of the evidence ranged from very low to moderate. The main limitations were risk of bias (associated with poor reporting of methods) and imprecision.
This review found few differences in newborn or maternal outcomes for pregnant, opiate-addicted women who were maintained on methadone, buprenorphine or oral slow-release morphine from a mean gestational age of 23 weeks to delivery. Only four randomised controlled trials with 271 participants trials satisfied the inclusion criteria for the review: two from Austria (outpatients), one from the USA (inpatients) and the fourth a multi-centre, international study conducted in Austria, Canada and the USA. The trials continued for 15 to 18 weeks. Three compared methadone with buprenorphine (223 participants) and one compared methadone with oral slow-release morphine (48 participants). The number of women who dropped out from treatment was lower in the methadone group. However, there was no difference in the use of primary substance between the methadone and buprenorphine groups. The number of newborns treated for neonatal abstinence syndrome did not differ significantly between groups. Birth weight was higher in the buprenorphine group in two trials and no different in the third. Oral slow-release morphine seemed superior to methadone in terms of the number of women who used heroin in their third trimester. However, there was no clear improvement in infant birth weight or duration of neonatal abstinence syndrome. The number of participants in the trials was small and may not be sufficient to draw firm conclusions. All the included studies ended immediately after the baby was born. No severe complications were noted.
We found four studies of MN involving a total of 831 participants who more than three months poststroke, with mean ages from 53 to 64 years. All participants were able to walk from less than 0.5 m/s to more than 0.7 or even 0.9 m/s. The included studies were published between 2007 and 2015 in the USA and the Netherlands. All included studies applied MN directed to a nerve in the leg (peroneal nerve) to promote the contraction of a muscle at the front of the leg, thus preventing the foot 'dropping' as the leg was swung forward while the participant walked. MN was used from up to eight hours per day to all-day use for walking about in the natural environment in which people live. Three studies used an MN device that interfaces with the nervous system through electrodes positioned over the skin in the projection of the peroneal nerve in the leg. Only one study used a implantable device whose electrical stimulus is released directly on the nerve by electrodes placed under the layer that surrounds the nerve. All studies compared MN versus ankle-foot orthosis (AFO), that is an assistive device usually made of a rigid material and placed externally on the lower leg to hold the foot and ankle to prevent the foot dropping. There is limited evidence that people after stroke who receive MN as an orthosis for walking in the home or community context may not improve activities involving limbs such as walking speed between 6 and 12 months of device use (low-certainty evidence), Timed Up and Go (moderate-certainty evidence), and modified Emory Functional Ambulation Profile (low-certainty evidence); as well as participation scale of health-related quality of life (very low-certainty evidence), exercise capacity (low-certainty evidence), and balance (moderate-certainty evidence), compared with people after stroke who receive AFO. There was evidence of an effect that the control intervention (AFO) attained a higher walking speed after six months of device use (low-certainty evidence), but this evidence showed that the improvements were too small to indicate a meaningful change to patients, and when we excluded the study in which the people that assessed the outcomes were aware of the intervention details, this effect was no longer found. There was no difference in effects on walking speed between MN with surface versus MN with implantable electrodes. No study reported outcomes related to independence in activities of daily living. The majority of studies reported adverse events such as falls and serious adverse events related to device use, which were found to be similar for MN and AFO use (moderate- and low-certainty evidence, respectively). One study considered serious adverse events related to device use as serious falls. More people who received MN withdrew from the studies than did people who received AFO (low-certainty evidence). The results of this review indicate that little is known about the effects of MN and that further information is required. It is unknown if people less than three months poststroke could benefit from MN use as an assistive device to perform activities in daily life. The impact of MN applied to the upper limb or MN that uses brain or muscle signals to trigger the stimulation is unknown in people with stroke. We found no evidence evaluating the costs of delivering MN. The certainty of the evidence ranged from moderate to very low.
We found 11 studies that assessed recruitment strategies used with healthcare staff in search of the literature in January 2015. Five included the total number of participants (7372). There were three main strategies: 1. Using an alert system, either a computer system or member of staff to check patient records, to alert staff recruiting participants that someone might be suitable for the study (five studies). 2. Giving additional information about the study to the staff at hospitals or clinics who are recruiting people through visits from the researchers, educational seminars or leaflets (four studies). 3. Using a designated member of staff whose primary role was to recruit participants (two studies). All the studies identified were of quite low quality, so it is difficult to draw firm conclusions from them. Five studies examined the alert system to identify participants who might be suitable for a study. Alert systems showed some promising results but were not unanimous in their findings. The four studies that evaluated the provision of additional information, visits or education to the sites recruiting participants found that none of the tested strategies led to improved recruitment. The most promising strategy appears to be the employment of someone such as a clinical trials officer or research nurse with the specific task of recruiting participants to research studies. The two studies using this strategy showed improvement in recruitment rates but both were at high risk of bias. More research is still needed to evaluate the role of a designated person to recruit to research studies.
This review looks at studies that compare the regular use for at least four weeks of different types of inhaled short-acting bronchodilator medication in people with chronic obstructive pulmonary disease (COPD, or emphysema/chronic bronchitis). There were eleven trials included. There were no major differences seen between the responses to ipratropium and salbutamol, or the combination. Where there were benefits, they were small and would not support a general recommendation for the use of ipratropium bromide or a combination with beta-2 agonist over a beta-2 agonist alone in COPD. People with COPD could use the short-acting bronchodilator that gives them the most improvement in their symptoms.
We found 23 studies. Two studies were randomised controlled trials with 1414 workplaces. Fifteen non-randomised studies analysed injury rates of firms obtained from large administrative databases. Six studies with more than 340 participants in total reported on the opinions of workers or employers. Two studies randomly allocated inspections or no inspections to workplaces. After one year follow-up the non-fatal injury rate in one study and the frequency of physical overload in the other study were still similar in both study groups. Another five similar but lower quality studies had inconsistent results at short and medium-term follow-up. Two other non-randomised studies found that after more than three years inspections decreased injuries and accidents by 23% compared to no inspections and there was no effect on the firms' productivity. Specific inspections resulted in higher compliance rates. Inspections with penalties could result in fewer injuries and more compliance in the short term in small firms. Longer inspections and more frequent inspections probably do not result in more compliance. Two studies did not find a harmful effect of inspections on firm lifetime or employment. Qualitative studies showed that there is support for enforcement among workers. However, workers doubt if inspections are effective because they are rare and violations can be temporarily fixed to mislead the inspectors. We concluded that inspections decrease injuries in the long term but probably not in the short term. The evidence is of low to very low quality because the results across studies are inconsistent and studies are observational and do not take into account other factors that could affect the results. In addition, the magnitude of the effect is uncertain because it varies from a 3 to 23 per cent decrease in injury rates. Because the quality of the evidence is low, future studies can easily change our conclusions. There is an urgent need for large-scale randomised trials to evaluate different types of inspection methods on exposure, disorders and injuries.
We searched the medical literature to 19 May 2017 and found nine randomized (clinical studies where people are randomly put into one of two or more treatment groups) or partly (quasi) randomized trials (including 658 participants) that assessed the efficiency of IVIg in infants with alloimmune HDN. Analysis of all included studies showed a reduction in the need for and number of ETs in infants treated with IVIg combined with phototherapy compared to infants treated with phototherapy only. However, this was not confirmed in an analysis of the two placebo-controlled studies (where a pretend treatment was given). There was no difference in the need for or number of top-up transfusions. The evidence from the studies was very low quality. However, two studies used a placebo, thereby minimizing bias and allowing blinding of the researchers assessing the response. These studies were consistent with each other and yielded moderate quality evidence (with a relatively small total number of participants involved (172) being the only reason to not regard the level of evidence from them as high) that IVIg was ineffective in preventing ET or top-up transfusions. Based on all included studies, we could make no conclusions on the benefit of IVIg in preventing ET or top-up transfusion. However, the two placebo-controlled trials provided evidence of moderate quality that IVIg was ineffective in preventing ET or top-up transfusion, and therefore routine use in alloimmune HDN should not be recommended. However, since there was some evidence that IVIg reduced hemolysis (in laboratory studies), future high-quality studies are needed to determine whether IVIg has limited role in some infants with alloimmune HDN.
Our search strategy was designed to identify randomized controlled trials (RCTs) where RSI was undertaken to secure an artificial airway for a general anaesthetic with or without the application of cricoid pressure. Vomiting or regurgitation of stomach contents during anaesthesia was to be assessed either by looking directly down the airway or by various laboratory and imaging (radiological) methods. We also set out to determine whether applying cricoid pressure caused any harm. We searched the databases until May 2015. Only one RCT met our inclusion criteria but unfortunately this trial did not report on any clinically relevant results. We classified one other trial as ongoing. The researchers have reported on their planned protocol for the clinical trial, where cricoid pressure applied using a measured force will be compared with cricoid pressure without measuring the force applied. The number of patients who vomit is to be monitored. This systematic review shows an absence of evidence regarding the effectiveness and risks of cricoid pressure during RSI for intubation. Little can be said therefore about whether this technique should be continued in clinical practice. One current ongoing study shows promise that it will provide useful information in the future.
In March 2015 we performed searches to look for new studies, and found only two additional small studies to include. Neither provided any good quality evidence for benefit or harm. There were still no studies that could provide an answer that was trustworthy or reliable, because most were relatively old, and used methods or reported results that we now recognise as making benefits seem better than they are. This is disappointing, but we can still make useful comments about the drug. Amitriptyline probably does provide good levels of pain relief for some people with fibromyalgia, although we cannot be certain of this. Our best guess is that amitriptyline provides good pain relief in about 1 in 4 (25%) more people than does placebo. About 1 in 3 (31%) more people than with placebo report having one or more adverse events, which are usually not serious but may be troublesome and interfere with taking the treatment. We cannot trust either figure based on the information available. The most important message is that amitriptyline probably does give really good pain relief to some patients with fibromyalgia, but only a minority of them; amitriptyline will not work for most people.
We reviewed the evidence on the effects of interventions in reducing waiting times. We found eight eligible studies (three randomised controlled trials and five interrupted time series studies) involving 135 primary care clinics, seven hospitals and one outpatient clinic. Different interventions, elective procedures and clinical conditions across included studies made pooling of data unfeasible. The quality of the included evidence (to November 2013) ranged from low to very low, as data were obtained from randomised controlled trials that for the most part suffered from serious bias, and from non-randomised studies without a control group. The single study that evaluated an intervention aimed at prioritising demand showed that introducing a system for streamlining elective surgery reduced the number of semi-urgent patients waiting longer than recommended, but did not affect urgent or non-urgent groups. Seven studies evaluated interventions aimed at restructuring the intake assessment/referral process. Three of four studies evaluating effects of open access or direct booking/referral showed beneficial effects: One study showed reduced waiting times for open access to sterilisation through keyhole surgery; another showed that open access to investigative services may lead to reduced waiting times for patients with urinary symptoms (but not for patients with microscopic blood in urine); and one study reported that same-day scheduling reduced waiting times for those seeking child health outpatient services. One study showed no effect of a direct booking system on the proportion of patients reported to have moderate or severe cell changes on the neck of the womb who received an appointment for further investigation within four weeks. Two studies of distant consultancy (instant photography for skin conditions and telemedicine for ear, nose and throat conditions) showed no effect on waiting times to see a specialist. One study reported that using a pooled waiting list did not change the number of patients waiting for routine back surgery within the recommended time. We found no studies evaluating interventions aimed at increasing capacity or rationing demand. As only a handful of low-quality studies are presently available, we cannot draw any firm conclusions about the effectiveness of the evaluated interventions in reducing waiting times. However, interventions involving the provision of more accessible services (open access or direct booking/referral) show some promise.
We looked for all studies in people with pancreatic cancer that could not be operated on (locally advanced) or that had already spread beyond the pancreas (metastatic). We found 42 clinical studies involving 9463 participants who were receiving their first therapy for PC. Our search is current to June 2017. The studies compared one therapy against either best supportive care (symptom management only) or another type of therapy. Studies had to evaluate overall survival (or time to death). The study could be testing either chemotherapy (drugs that kill or slow the growth of cancer cells) or radiotherapy (X-ray treatment). We collected data on survival, tumour response rate, side effects and quality of life. The results of clinical studies addressing targeted/biological therapies, immunotherapies, second-line therapies and local treatments for locally advanced disease will be reported in a separate Cochrane Review. This review has shown that in advanced disease, combination chemotherapy with FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin combination); GEMOXEL (gemcitabine, oxaliplatin and capecitabine); cisplatin/epirubicin/5FU/gemcitabine; gemcitabine plus nab-paclitaxel; and gemcitabine plus a fluoropyrimidine agent, provide a survival advantage over gemcitabine alone. These combinations do increase side effects. Gemcitabine given slowly using a fixed rate of infusion may be more effective than giving it in the standard way, which is quickly over 30 minutes. The quality of the evidence varied greatly amongst comparisons. The highest quality evidence was for gemcitabine versus fixed dose rate gemcitabine and some of the gemcitabine combinations (fluoropyrimidine, topoisomerase, and taxane). We judged the studies for quality using factors like how well they were conducted, how well they reported results and whether they used a placebo.
We searched the medical literature up to 26 January 2017. All randomised trials that compare two different antibiotics, or variations in dosing of a single antibiotic for treatment of CDI were included. Trials comparing antibiotic to placebo (e.g. a sugar pill) or no treatment were sought but, save for one poor quality placebo-controlled trial, none were found. Trials that compared antibiotics to a non-antibiotic treatment were not included. Results Twenty-two studies (total 3215 participants) were included. The majority of studies enrolled participants with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded participants with severe CDI and few participants with severe CDI were included in the other studies. Twelve different antibiotics were assessed. Most of the studies compared vancomycin or metronidazole with other antibiotics. One small study compared vancomycin to placebo (e.g. sugar pill). There were no other studies that compared antibiotic treatment to a placebo or a no treatment control group. Seventeen of the 22 included studies had quality issues. In four studies, vancomycin was found to be superior to metronidazole for achieving sustained symptomatic cure (defined as resolution of diarrhoea and no recurrence of CDI). We rated the quality of the evidence supporting this finding as moderate. A new antibiotic, fidaxomicin, was, in two large studies, found to be superior to vancomycin. The quality of the evidence supporting this finding was moderate. It should be noted that the differences in effectiveness between these antibiotics were not too great and that metronidazole is far less expensive than either vancomycin and fidaxomicin. A pooled analysis of two small studies suggests that teicoplanin may be more effective than vancomycin for achieving symptomatic cure. The quality of the evidence supporting this finding was very low. The quality of the evidence for the other seven antibiotics in this review was very poor because the studies were very small, and many patients dropped out of these studies before completion. One hundred and forty deaths were reported in the studies, all of which were attributed to participants preexisting health problems. The only side effects attributed to antibiotics were rare nausea and temporary elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13. Vancomycin 125 mg costs USD 1779 compared to fidaxomicin 200 mg at USD 3453.83 or more and teicoplanin at approximately USD 83.67. Conclusion No firm conclusions can be drawn regarding the effectiveness of antibiotic treatment in severe CDI as most studies excluded these patients. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the antibiotic that caused CDI. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other antibiotics. The quality of evidence for teicoplanin is very low. Larger studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin would be of interest.
We included 10 randomised controlled trials with a total of 3575 participants. We found that medication review does not seem to prevent death and hospital readmissions, but that it might reduce emergency department contacts. Our confidence in results across studies ranged from low to high. We found no evidence that medication review in hospitalised patients makes a difference towards preventing mortality (low-certainty evidence) or hospital readmissions (high-certainty evidence), but we found that medication review may have a preventive effect on reducing the number of emergency department contacts (low-certainty evidence). In the included trials, participants were followed for a short time (ranging from 30 days to one year). Therefore, important long-term treatment effects may have been overlooked. We suggest that further research with long-term patient follow-up and examination of specific methods of medication review should be undertaken before this intervention is implemented in clinical practice.
The efficacy of this approach is difficult to assess and there have been few research studies of good quality. The current review sought to review studies evaluating the success of community-based programmes specifically intended to reduce burn and scald injury in children. Only four studies were identified that met the inclusion criteria and two of these found a reduction in rates of burns and scalding. More high-quality research studies are needed in this area, therefore, to support the continued use of the community approach.
We included six randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups). The duration of the treatments ranged between 3 and 7.6 years. Study authors allocated 498 participants to treatment groups, 267 participants to oxandrolone plus growth hormone treatment and 231 participants to growth hormone only treatment. The average age of the children at begin of treatment ranged from 9 to 12 years. This evidence is up to date as of October 2018. When comparing oxandrolone plus growth hormone to growth hormone only, the final adult height was on average 2.7 cm higher in favour of oxandrolone plus growth hormone therapy. Only two studies provided reliable data on side effects: 6 out of 86 (19%) participants given oxandrolone plus growth hormone compared with 8 out of 84 (10%) participants given growth hormone only reported side effects, mainly signs of development of male physical characteristics (for example deepening of the voice). One study investigated the effects of treatments on speech, the process of acquiring knowledge and understanding (cognition), and mental and emotional (psychological) status. The overall results for these were inconclusive. No trial measured people's satisfaction with their life and health or death from any cause. For side effects and effects on speech, cognition and psychological status, we are uncertain or very uncertain, mainly because the number of studies and participants was low and results were vague. For final adult height, we think that further research is likely to have an important impact on our confidence in the results and may change the results.
Twenty-seven studies involving 11,398 participants were included for analysis. The main results were a reduction in in-hospital complications and improved documentation associated with clinical pathways. Complications assessed included wound infections, bleeding and pneumonia. Most studies reported a decreased length of stay and reduction in hospital costs when clinical pathways were implemented. Considerable variation in study design and settings prevented statistical pooling of results for length of stay and hospital costs. Generally poor reporting prevented the identification of characteristics common to successful clinical pathways. The authors concluded that clinical pathways are associated with reduced in-hospital complications
We identified seven randomised trials—involving a total of 1474 patients. Only one study compared total disc replacement with nonsurgical treatment, suggesting that surgery resulted in slightly better outcomes than intensive rehabilitation. But this did not translate into a clinically significant advantage that would make a major difference in patients’ lives. Six randomised trials compared disc replacement with spinal fusion surgery. Most of these studies had a high potential for bias, raising the possibility that they might not have provided a fair test of the treatments under study. These trials found that patients who underwent total disc replacement had slightly better outcomes in terms of back pain and function than those who had fusion surgery. But again the differences did not appear clinically significant. The review could not find evidence of any other benefits of total disc replacement, and the studies provided no insights on the long-term risks associated with it. Given the gaps in the evidence, the review concluded that the spine surgery community should be prudent about adopting this technology on a large scale.
In this updated review, we examined the evidence from two randomised trials of NIV in ALS involving a total of 54 participants. One of the trials, which studied when to start NIV, provided no usable data. A third trial, identified in a clinical trials register, currently has no published results. Complete data were only available from a single trial of 41 participants. The results of this trial provided moderate-quality evidence that NIV significantly prolongs survival, and low-quality evidence that it improves or maintains quality of life compared to standard care. Median survival was increased by an estimated 48 days, from 171 to 219 days. The survival benefit from NIV was much greater in people with ALS in whom the muscles used for speaking, chewing, and swallowing (bulbar muscles) were either unaffected or only moderately weak. Among these 20 participants, the median survival with NIV was increased by an estimated 205 days (216 days with NIV, compared to 11 days with standard care). Quality of life was also maintained in participants with mild to moderate bulbar weakness. In the 21 participants with severe bulbar weakness, NIV did not prolong survival or maintain quality of life scores, although a sleep-related symptoms score improved. Neither trial reported on adverse effects. Participants and clinicians were aware of the treatment groups, which can influence quality of life assessments. More trials of NIV versus standard care in ALS are unlikely as it would not be ethical to withhold NIV. Future studies should examine early intervention with NIV and determine the best time to start it. The evidence is up to date to January 2017.
In this review we looked at studies that provided personalised risk information for each participant, so that he or she could make a decision about whether to undergo screening, based on their personal risk profile. We found 41 studies with 28,700 participants that provided such personalised risk information to the participants. We integrated the results of all these studies and found that when such a risk profile was included in the intervention, the participants made more informed decisions about screening, compared to people who were provided with more general risk information. Overall 45.2% (592/1309) of participants who received personalised risk information made informed choices as compared to 20.2% (229/1135) of participants who received generic risk information. We also found that these interventions seemed to increase knowledge and may increase accuracy of risk perception in the trial participants. However they did not significantly affect participants' anxiety. The results also indicated that providing people with personalised risks of the disease resulted in a small increase in the number of people who undertook the screening procedure. The results from this review are dominated by studies screening for breast cancer and colorectal cancer. Caution is required in applying these results to other types of screening.
We included two randomized controlled trials that compared fluocinolone acetonide implants with standard-of-care therapy. These studies included 401 participants from Australia, France, Germany, Israel, Italy, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, the United Kingdom, and the United States who were 6 years old or older and were followed for two years. The evidence is current to 6 November 2015. Since the two studies were designed to answer slightly different questions about the fluocinolone implant, we were not able to combine data from both studies to compare how well the medications worked. However, we were able to do a combined analysis of the common side effects, which suggest that participants in the steroid implant group had more surgery for cataract (clouding of the lens of the eye) and for high eye pressure than participants in the non-implant group. We were unable to determine whether the steroid implants were better than standard-of-care therapy. The overall quality of the presently available published evidence was moderate. This finding indicates that future published research is likely to have an important impact on the conclusions currently provided in this review.
We found four studies with 1029 participants. All four studies compared participants taking tapentadol to participants taking similar medicine, such as morphine or oxycodone. All studies gave participants a period of time to find the best dose to take, before continuing on the medication and comparing their pain levels. All the studies were small or medium sized, so the results are at risk of being influenced by random fluctuations rather than real differences, and they may also overestimate any effects. One trial allowed participants to know what medication they were taking, and one trial was stopped early due administrative problems, so they did not have enough people in the study. We have to be cautious interpreting results from these studies. Because the studies all used different designs, we could not compare the results from one with another. However, each study showed that there was not much difference between the pain levels of people taking tapentadol and people taking morphine and oxycodone. Pain levels were generally well controlled. The studies also showed there was no measurable difference in how many adverse effects people had while taking tapentadol, morphine, or oxycodone. Therefore, we can conclude only that the studies to date show tapentadol was no more or less effective and no more or less well tolerated than morphine and oxycodone.
To date, 1651 infants (between eight and 28 days of age) born preterm have been enrolled in 31 studies of late administration of EPO to reduce the use of red blood cell transfusions and to prevent donor exposure. There were no studies that used darbepoetin. We have not received any funding for this review and we have no conflicts of interest to declare. The risk of receiving red blood transfusion is reduced following initiation of EPO treatment. However, the overall benefit of EPO is reduced as many of these infants had been exposed to donor blood prior to entry into the trials. Treatment with late EPO did not have any important effects on death or common complications of preterm birth, except for trends towards an increased risk for retinopathy of prematurity. Retinopathy of prematurity is a disease of the eye affecting infants born preterm. It is thought to be caused by disorganised growth of retinal blood vessels, which may result in scarring and retinal detachment. Retinopathy of prematurity can be mild and may resolve spontaneously, but it may lead to blindness in serious cases. The study quality varied and important information regarding the random sequence generation and whether the allocation was concealed or not was often missing. Sample sizes were small and long-term outcomes (18 to 24 months of corrected age) were not reported. The quality of the evidence was very low for the outcomes of "use of one or more red blood cell transfusions," "retinopathy of prematurity (all stages or stage not reported)" and for "retinopathy of prematurity (stage ≥ 3)". For the outcomes of "necrotising enterocolitis" and "mortality", the quality of the evidence was moderate.
In December 2015, we updated searches from an earlier Cochrane review to look for clinical trials that used oxycodone to treat neuropathic pain in adults. We found two additional studies to include. The earlier review included three studies that compared oxycodone with placebo over several weeks, and the additional studies added oxycodone to existing treatment with pregabalin or gabapentin. Most of the 687 people in the studies had painful limbs because of damaged nerves caused by diabetes. Only very low quality evidence suggested that oxycodone relieved the pain. Compared with placebo, fewer people stopped taking oxycodone because they felt it was not effective, but more people experienced side effects. We rated the quality of the evidence for both benefit and harm as very low because of small numbers of studies and participants, the outcomes reported, and potential bias from the way the studies were analysed. Very low quality evidence means that we are very uncertain about the results.
In the trials treating otitis media, the quality of the evidence was moderate as the methods for avoiding bias were not clearly stated. Furthermore, in one trial a pharmaceutical company prepared the placebo syrup used in the trial. In the study treating pneumonia, we classified the quality of the evidence as moderate, because the families previously knew if their children were receiving antibiotics or not. Furthermore, the methods for avoiding bias were not clearly stated by the trial authors. Further high-quality research is needed to provide more definitive evidence of the effectiveness of antibiotics in this population.
We searched for trials up to August 2015 and included 20 randomised controlled trials involving 1574 participants, of puerarin for people with ischaemic stroke. Only two trials reported death or dependency at the end of follow-up. The remaining studies followed participants for less than one month. We included 20 RCTs with 1574 participants in this updated review; five trials were new. Treatment with puerarin did not reduce death or dependency at final follow-up. Puerain improved neurological deficit at the end of treatment. The included trials did not report serious adverse effects. The quality of evidence was low due to incomplete reporting of the methods and short-term follow-up.
We found three randomised controlled trials. The searches are up to date to September 23rd 2014. A total of 953 people with age-related cataract in India and Nepal were randomly allocated to MSICS and ECCE in these trials. The data were limited. People whose lens was removed with MSICS were more likely to achieve good functional vision, however, overall not more than 50% of people achieved good functional vision in the two studies. 1.2% of people enrolled in two trials had a poor outcome after surgery with best-corrected vision less than 6/60. There was no evidence of any difference between the two groups with respect to this outcome. Surgically induced astigmatism was more common with the ECCE procedure than MSICS in the two trials that reported this outcome. In one study there were more intra- and postoperative complications in the MSICS group. One study reported that the costs of the two procedures were similar. We judged the quality of the evidence to be low or very low. There were only three studies and we could not combine the data because of differences in reporting and inconsistency between trials which meant that some of the results were imprecise.
Three randomised clinical trials were included. Due to their poor methodologic quality and the existing small number of trials, there is currently insufficient evidence for treating asymptomatic hepatitis B virus carriers with Chinese medicinal herbs like the herbal compound 'Jianpi Wenshen recipe', Phyllanthus amarus and Astragalus membranaceus. Methodologically better and larger randomised trials are needed comparing medicinal herbs versus placebo.
Systematic reviews can help with this process by bringing together the relevant evidence and using clear methods which seek to minimise bias. Interventions to help improve the uptake of systematic review evidence have been developed to help with improving the use of evidence. We identified eight studies which evaluated the effectiveness of these types of interventions. There was some evidence to show that a clear message, based on systematic review evidence, which is targeted and disseminated to the relevant healthcare professionals may improve evidence-based practice. If the aim is to help decision-makers increase their awareness and knowledge of systematic review evidence, and evidence-based practice, then interventions that address some of these aims have been evaluated but have shown little effect on practice.
The evidence is current to August 2014. We included 12 studies (430 participants). People of all ages were included in the studies, which were conducted in high-income countries. Eleven studies (389 participants) compared injecting antibodies into the muscle or vein of participants to injecting salt water or giving no treatment. The study participants did not have their own antibodies. They had been in contact with rubella between one and 28 days prior to receiving the antibodies. The antibodies seemed to be effective at preventing participants from catching rubella, with those receiving antibodies 39% less likely to develop rubella than those not given antibodies. In an analysis of the seven studies (89 participants) where participants had been in contact with rubella only up to five days earlier, people given the highest doses used in the studies were 80% less likely to develop rubella than those not given antibodies. The studies assessing the prevention of rubella were of moderate quality because of some methodological issues and the fairly small number of participants. It is important to consider that the amount of rubella antibodies in today's blood donations may differ from those used in the studies. Therefore, doses given today may need to vary from those of the studies in order to obtain the same effect. Only one study included pregnant women. All of the women were given one of two different doses of antibodies. They did not measure whether the babies born to the women were infected with rubella, but did consider whether birth defects that may be related to rubella were present. Key details about the study methods were missing and unobtainable, so the quality of this study was unclear. None of the babies born to these women were identified as having birth defects related to rubella. However, we cannot draw direct conclusions from this single study about the effectiveness of injecting antibodies after contact with rubella for preventing rubella-related birth defects in pregnant women. This is an area that needs further research. The included studies did not report adverse events. Future studies should report this outcome.
We searched for clinical trials in adults who had percutaneous coronary intervention for the management of heart attack and multi-vessel disease. The evidence is current to 4 January 2017. Only four trials reported funding from government organisations or charitable institutions. The other trials did not mention the source of funding and no private companies were mentioned as sources of finance. In the included trials, both the participants and researchers were aware of what treatment the participants received which may have biased the results. One trial ended enrolment earlier than planned because the difference between treatment was significant. This may have overestimated the difference between intervention groups. For most trials, the number of participants that were included was not enough to see a potential difference between treatments. We included nine clinical trials with 2633 people with heart attack and multi-vessel disease. Compared with participants who underwent opening of only the coronary artery that caused heart attack, people who underwent treatment on all narrowed vessels had fewer deaths from diseases of the heart and blood supply (called cardiovascular disease), required fewer treatments to open the problematic coronary arteries, and had fewer heart attacks at the end of one year or later since the treatment. Based on our analyses, although the treatment on all narrowed vessels appears to be a better treatment strategy, there still exists a need for more well-designed clinical trials to confirm that this approach is associated with fewer deaths from cardiovascular diseases or heart attack, or both. The evidence is of very low quality. For instance, the number of participants in the included studies was insufficient, the medical team was aware of the study group that the participants were allocated to and that may have affected our conclusions. There is a need for well-designed clinical trials with more participants to determine which treatment strategy is superior.
This review found a single randomised controlled trial that examined the short-term effects of cooling plus xenon for infants with HIE. This trial enrolled 92 participants. Cooling plus xenon did not improve clinical outcomes before discharge from the hospital compared with cooling alone. Data on long-term development were not provided. Current low quality evidence is inadequate to show whether cooling plus xenon improves survival and development of newborn babies with HIE. Evidence is up-to-date as of August 2017.
Fifteen trials provided data for this review; 1034 adult participants were randomly assigned to vitamin D compared with placebo or no treatment. Nine trials were conducted in high-income countries, and six trials in middle-income countries. All trials were at high risk of bias (that is overestimation of benefits and underestimation of harms). The age range of the participants was 18 years to 84 years and on average 42% were women. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. Most of included trials reported the baseline vitamin D status of participants. Vitamin D administration lasted on average six months and most trials used the cholecalciferol (vitamin D3) form. Six trials appeared to be free of industry sponsorship or other type of for-profit support that may bias the results of the trials. Eight trials may not have been free of for-profit bias as they did not provide any information on clinical trial support or sponsorship. One trial was funded by industry. This review suggests that vitamin D has no beneficial or harmful effects on chronic liver diseases. However, there were too few trials on the individual diagnosis of chronic liver diseases and there were too few participants in the individual trials as well as in our meta-analysis. Therefore, neither benefits nor harms can be excluded. All trials were judged to be at high risk of bias (that is, possibly an overestimation of benefits and underestimation of harms). This evidence is up to date as of January 2017.
We identified 11 trials (with 3352 participants older than 12 years with a diagnosis of community-acquired pneumonia), fully published in peer-reviewed journals, focused on treatment of pneumonia in adolescents and adults treated in the community in outpatient settings. This included five new trials included since our last review published in 2009. None of the trials included antibiotics versus placebo; all trials included one or more antibiotics. All participants were diagnosed with pneumonia based upon clinical diagnosis by the physician and chest X-ray. All included trials were well conducted; nine of the 11 trials were sponsored by bio-pharmaceutical companies manufacturing the antibiotics used in the study, or their authors were closely linked with the company. Nine of the included trials compared different antibiotics and, hence, we could not combine the results of the individual trials to present our overall conclusion. There were some notable adverse events in seven studies: 1) erythromycin demonstrated significant gastrointestinal side effects compared to clarithromycin in two studies; 2) nemonoxacin demonstrated higher gastrointestinal (nausea, diarrhoea) and nervous system (dizziness, headache) adverse events compared to levofloxacin; 3) cethromycin demonstrated more side effects, especially a distortion of the sense of taste, than clarithromycin; 4) gastritis and diarrhoea were more common in the high-dose amoxicillin group (1 g three times a day) compared to the other three antibiotic groups (clarithromycin, azithromycin and levofloxacin). Unfortunately, there were not enough trials to compare the effects of different antibiotics for pneumonia acquired and treated in the community.
The review found that there was not enough evidence to reach clear conclusions about the effects on any of these outcomes and it is therefore not clear to what extent the application of mistletoe extracts translates into improved symptom control, enhanced tumour response or prolonged survival. Adverse effects of mistletoe extracts were reported, but appeared to be dose-dependent and primarily confined to reactions at injection site and mild, transient flu-like symptoms. In the absence of good quality, independent trials, decisions about whether mistletoe extracts are likely to be beneficial for a particular problem should rely on expert judgement and practical considerations.
People infected with HIV/AIDS require an antiretroviral regimen that works well, has good activity against the virus, has few adverse effects (unintended negative effects of the drug) and that does not interact with other drugs. The regimen of nevirapine, stavudine and lamivudine is widely used as first-line therapy, and is recommended as such by the World Health Organization for so-called low-resource countries (in other words, for poor countries). This review identified two randomised controlled trials that assessed the efficacy of this drug combination. One trial was a small single-centre Australian trial of 70 participants, whereas the other trial was a large, multicentre trial, conducted in 14 countries, of 1,216 participants. In both trials over 60% of participants were male and none had been on previous antiretroviral treatment. As one trial was very small, we cannot be sure of its results. The main findings therefore come from the much larger trial. This trial compared the combination of nevirapine, stavudine and lamivudine with the combination of efavirenz, stavudine and lamivudine, and found that participants had similar treatment outcomes on either combination. It also found that taking nevirapine once a day with twice daily stavudine and lamivudine worked as well as taking nevirapine twice a day in combination with twice daily stavudine and lamivudine. Nevirapine did appear to cause more adverse effects compared with efavirenz, but additional assessment of this is necessary to be more certain. It is important that more trials which follow participants for a longer time be done to provide better evidence for the use of this combination as a first-line therapy. A trial assessing fixed-drug (providing drugs in a single tablet) is also required, as this reduces the number of pills people must take each day. These studies should include assessment of adverse effects, as well as tracking whether resistance to the drugs develop over time.
The overall quality (certainty) of the evidence was moderate to very low for all of the outcomes, mainly because of the small number of studies and low number of participants, as well as study limitations. The findings of this review should be interpreted with caution due to the overall low-certainty of the evidence, variation in cancer types and treatments, exercise interventions, and outcomes measured. We are moderately certain that exercise training during adjuvant treatment (chemotherapy or radiotherapy treatment after surgery) reduces fatigue. This is a new area of research, and more information is needed to help us understand whether exercise benefits people undergoing cancer treatment. Future studies should also concentrate on people with a new diagnosis of cancer who have chemotherapy or radiotherapy prior to surgery (known as neoadjuvant treatment), to tell us whether exercise training prior to surgery is important.
Researchers of the Cochrane Collaboration conducted a review of research about the effects of antidepressants classified as serotonin reuptake inhibitors (SSRIs) on fibromyalgia. After searching for all relevant studies up to June 2014, they found seven studies that compared SSRIs with a fake medication. These studies included a total of 383 people. Most participants were middle-aged women. The SSRIs that they studied were citalopram, fluoxetine and paroxetine. Five studies were each funded by pharmaceutical companies, and two studies were funded by public institutions. Key results We are uncertain of the evidence of the outcomes of reduction of pain, sleep problems, fatigue, depression, global improvement (proportion of patients who reported to be much or very much improved), tolerability (dropout rates due to adverse events), and safety (serious adverse events). Possible side effects of SSRIs may include dry mouth, nausea/vomiting, and sexual dysfunction. Rare complications may include allergies, diseases of the immune system, liver damage, and impairment of a person’s ability to drive or operate machinery; serious side effects, such as suicidal thoughts and liver failure, are very rare.  What is fibromyalgia and what are serotonin reuptake inhibitors? People with fibromyalgia suffer from chronic widespread pain, sleep problems, and fatigue. There is no cure for fibromyalgia at present. Treatments aim at relieving the symptoms and improving health-related quality of life. Serotonin is a chemical which is produced by the human body and is involved in the experiences of pain, sleep, and mood. Decreased concentrations of serotonin have been reported in people with fibromyalgia. SSRIs are antidepressants that increase the concentration of serotonin in the brain. SSRIs are not approved for use as fibromyalgia treatment, but are approved for depression and anxiety disorder. Quality of the evidence The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. Therefore we are uncertain whether taking SSRIs for an average of eight weeks improves fibromyalgia symptoms (number of people who reported that their pain was reduced by at least 30%, and number of people reporting a clinically important global improvement in pain intensity, fatigue, sleep problems, and depression). This is the Abstract and Plain Language Summary of a Cochrane Review, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue X, Copyright © 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd. The full text of the review is available in The Cochrane Library (ISSN 1464-780X).  This record should be cited as: Walitt B, Urrútia G, Nishishinya MB, Riera Lizardo RJ, Cantrell SE, Häuser W. Selective serotonin reuptake inhibitors for fibromyalgia syndrome. Cochrane Database of Systematic Reviews [Year], Issue [Issue].
We included 35 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 10,703 participants. Most participants were men (77%), and had recently had a heart attack or undergone a surgical revascularisation procedure. Studies followed up participants for between six months and 10.7 years, with 12 months being the most common period. At baseline (start of the trial), 10 trials only recruited participants with CHD and an established psychological condition (mostly depression), 11 trials recruited people with varying levels of psychopathology, three studies excluded people with psychological conditions, and 11 studies did not report psychological status. Study funding Thirteen studies did not report funding sources. Seven studies were funded by government grants, six through charitable foundations, and six through a mix of government and charitable funding. Two studies reported receiving some funding from private companies in addition to funds secured from government and charitable sources, and one study was university funded. Key results Psychological interventions did not reduce mortality (any cause), or the risk cardiac surgery or having another heart attack. Psychological interventions reduced the risk of cardiac deaths and reduced participant-reported symptoms of depression, anxiety, and stress. Quality of the evidence There is considerable uncertainty regarding the effects observed, as the quality of the evidence was either low (for cardiac mortality, non-fatal heart attack, depression, anxiety) or very low (for stress) for most measures, except deaths (any cause) or cardiac surgery, both of which had moderate quality of evidence.
This review included 25 studies with a total of 2310 children that compared ten different agents to either placebo (inactive medications) or each other. Many of the studies were small in size and were judged to be of poor or unclear quality. The results of this review suggest that PEG preparations may increase the frequency of bowel movements in constipated children. There is evidence from one study that suggests that high dose PEG (0.7 g/kg) may be superior to low dose PEG (0.3 g/kg) for increasing the frequency of bowel movements in constipated children. The rates of minor side effects were generally lower compared to other agents. Common side effects included flatulence, abdominal pain, nausea, diarrhoea and headache. There was also some evidence that liquid paraffin (mineral oil) increased the frequency of bowel movements in constipated children. Common side effects with liquid paraffin included abdominal pain, distention and watery stools. There was no evidence to suggest that lactulose is superior to the other agents studied, although there were no trials comparing it to placebo (a fake medicine such as a sugar pill). These studies were relatively short in duration and so it is difficult to assess the long term effectiveness of these agents for the treatment of childhood constipation. Long term effectiveness is important, given the often chronic nature of this problem in children. The results of the review should be interpreted with caution due to quality issues in the included studies. As such, the strength of our conclusions is extremely limited and more research is needed. Key questions that need addressing include the safety of liquid paraffin, given its apparent effectiveness, but limited investigation. In particular, future research should compare liquid paraffin to PEG. The optimal dose of PEG warrants further investigation. The role of PEG for the long term management of chronic constipation also needs further investigation to allow research to better inform actual clinical practice. There is a lack of studies comparing lactulose with placebo.
We identified five studies that had a total of 212 patients. All patients were under five years of age. The patients were given levosimendan during or immediately after heart surgery for a duration of 20 to 72 hours. They were monitored for 20 hours to six days. We asked all of the study authors for additional information about their trials. All but one author responded. The evidence is current to June 2016. We found low-quality evidence for all outcomes. This was mainly due to the small number of included patients (high imprecision of results). Thus, all results of the meta-analysis must be viewed with caution. The available data revealed no clear difference between levosimendan and conventional medication in preventing reduced heart function and death after heart surgery in the studied population. We also found no clear difference in the length of stay in the intensive care unit. The available data did not allow us to judge whether one of the treatment arms was superior to the other for three secondary outcomes: length of hospital stay, time on mechanical ventilation, need to implant circulatory support devices or the need for cardiac transplantation. Overall, few side effects were reported in any of the groups. We were unable to pool data to generate useful information about the safety of levosimendan.
We included nine randomised controlled trials (RCTs) with a total of 910 participants in this review. The studies varied in size: some were small, with as few as 20 patients, while others included over 200 participants. Most studies recruited adult patients, but one study only included children. In the majority of the adult studies, most participants were male (72% to 79%). In all of the studies the participants had chronic rhinosinusitis with nasal polyps. The studies either compared different types of steroids (three studies), high-dose versus low-dose steroids (five studies), twice daily versus once daily steroids, or different delivery methods (aqueous nasal spray versus aerosol - one study). All of the studies had a placebo group. Different steroids: fluticasone propionate versus beclomethasone dipropionate Two small studies (56 participants, unclear risk of bias) evaluated disease severity and looked at the primary adverse effect, epistaxis (nosebleed), but no other outcomes. No difference was found between the two steroids but we assessed the evidence to be of very low quality. Different steroids: fluticasone propionate versus mometasone furoate One study (100 participants, unclear risk of bias) found no difference in disease severity (nasal symptoms scores). We assessed this evidence to be of very low quality. High-dose versus low-dose steroids We found five studies (663 participants, low or unclear risk of bias) that compared high-dose and low-dose steroids, three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children), and two using fluticasone propionate drops (800 µg versus 400 µg). Effectiveness (disease severity and nasal polyps size) was similar between the high-dose and low-dose groups (low quality evidence). Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear because the improvements seen were small. The primary adverse effect, epistaxis, was more common when higher doses were used (moderate quality evidence). Different delivery methods: aqueous nasal spray versus aerosol spray We identified only one poorly reported study with a high risk of bias. It was unclear how many participants there were: 91 were recruited into three arms. There had also been significant differences between the participants in the two groups when they started the study. We were unable to draw any meaningful conclusions from this study. We found no evidence that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that higher doses are better than lower, nor that the effectiveness of a spray differs from an aerosol. We found no studies that compared nasal drops with spray. We did find moderate quality evidence of an increased risk of epistaxis (nosebleed) as an adverse effect of treatment when higher doses were used. More research in this area is clearly needed. In the future studies should be well designed: they should measure chronic rhinosinusitis-specific health-related quality of life and adverse effects as outcomes, and look at what happens to patients taking intranasal steroids in the longer term.
This review is current until December 2015. We included four trials involving 205 participants. All four studies assessed effects of HVHF compared with the current standard haemofiltration and included participants with severe sepsis or septic shock who had been admitted to an ICU. Three of the four studies were very small (fewer than 20 participants enrolled in each study). The maximum time that participants were followed up after inclusion in any of the studies was 28 days. Two studies received financial support from pharmaceutical companies, and one study received support from a health research organization. Key results Outcome data were limited - two trials reported death rates at 28 days and one reported death rates in hospital; in the fourth study, the number of deaths stated did not match the quoted mortality rates. One study reported length of stay in the ICU, and one provided data on organ dysfunction. Investigators described no complications. No clear evidence showed any benefit of HVHF in critically ill patients with severe sepsis or septic shock. Quality of evidence Evidence is insufficient to support the routine use of high-volume haemofiltration in patients with severe sepsis or septic shock. Studies included in this review reported relatively small numbers of participants and measured different outcomes; therefore, we judged the quality of evidence with respect to the impact of HVHF as low. Larger trials, carried out at many centres, are required for full assessment of clinically relevant outcomes and for evaluation of cost versus benefit.
One randomised controlled trial (current until August 2016), studying 100 male participants and comparing hand-assisted laparoscopic repair with EVAR, was included in this review. No in-hospital deaths occurred during the study. The trial showed that hand-assisted laparoscopic repair took longer to perform than EVAR but there was no difference in the number of patients with reduced blood flow to the leg following either treatment. At present, there is a lack of randomised controlled trials examining the comparative effectiveness and safety of laparoscopic repair of AAA. The quality of the available evidence was imprecise due to the inclusion of one small study and wide confidence intervals; and indirect because the study includes male participants only. Further research is required before conclusions can be made.
People with severe mental health problems often have difficulties with 'treatment compliance' i.e. following their treatment programme. They can have difficulty remembering to take medication or appointment times. Unpleasant side effects of medication can also lead to people stopping medication, and a lack of insight into their illness can mean they do not see the need to follow treatments. Non-compliance with treatment can lead to poor health outcomes and even relapses and hospitalisation. There are several methods healthcare professionals use to help people with serious mental illness improve compliance; once such method is prompting. The purpose of prompting is to help patients to follow the treatment instructions and keep the treatment appointment times by using reminders via telephone calls, personal visits or posted referral letter. More recently, Information and technology-based prompts are being used. This review investigates the effectiveness of ICT-based prompts in order to support treatment compliance among patients with serious mental illness. A search for randomised controlled trials was run in 2012. Two trials that compared the use of ICT prompting compared with standard care could be included. Review authors rated the quality of data in these as 'moderate' or 'low'. Because of the small amount of data, it is impossible to say whether ICT-based prompts are effective. Only one trial measured medication compliance. The study suggested that ICT-based prompts may help people take their medication, but clear evidence of a benefit is missing. There were some positive effects for patient insight. However, insight was only better in the medium term and appeared to show no difference in the short term. Further, some positive effect was found in patient satisfaction with treatment, although the results for the analyses were imprecise. Also, mental state and quality of life showed minor improvement. There were no clear evidence that either intervention is less acceptable than the other. Outcomes such as service use, behaviour, costs or adverse effects were not presented in the studies. There is an ongoing trial, but additional well-conducted trials are needed.
Two randomised controlled trials were identified; both were conducted in patients with yellow oleander poisoning. One trial investigated the effect of MDAC on mortality, the relative risk (RR) was 0.31 (95% confidence interval (CI) 0.12 to 0.83) indicating a beneficial effect. The second study found a beneficial effect of anti-digoxin Fab antitoxin on the presence of cardiac dysrhythmias at two hours post-administration; the RR was 0.60 (95% CI 0.44 to 0.81). Other benefits were also noted in both studies and serious adverse effects were minimal. Studies assessing the effect of antidotes on other cardenolides were not identified. One ongoing study investigating the activated charcoal for acute yellow oleander self-poisoning was also identified. There is some evidence to suggest that MDAC and anti-digoxin Fab antitoxin may be effective treatments for yellow oleander poisoning. However, the efficacy and indications of these interventions for the treatment of acute digitalis poisoning is uncertain due to the lack of good quality controlled clinical trials. Given pharmacokinetic differences between individual cardenolides, the effect of antidotes administered to patients with yellow oleander poisoning cannot be readily translated to those of other cardenolides. Unfortunately cost limits the use of antidotes such as anti-digoxin Fab antitoxin in developing countries where cardenolide poisonings are frequent. More research is required using relatively cheap antidotes which may also be effective.
This Cochrane Review summarizes trials evaluating the effects of reminder systems on attendance at tuberculosis (TB) clinics and completion of TB treatment. After searching for relevant trials up to 29 August 2014, we included nine trials, including 4654 people. What are reminder systems and how might they help? Effective treatment for TB requires people to take multiple drugs daily for at least six months. Consequently, once they start to feel well again, some patients stop attending clinics and stop taking their medication which can lead to the illness returning and the development of drug resistance. One strategy the World Health Organization recommends is that an appointed person (a health worker or volunteer) watches the person take their medication everyday (called direct observation). Other strategies include reminder systems to prompt patients to attend for appointments on time, or to re-engage people who have missed or defaulted on a scheduled appointment. These prompts may be in the form of telephone calls or letters before the next scheduled appointment ("pre-appointment reminders"), or phone calls, letters, or home visits after a missed appointment ("default reminders"). What the research says: For people being treated for active TB: - More people attended the clinic and completed TB treatment with pre-appointment reminder phone-calls (low quality evidence). - More people attended the clinic and completed TB treatment with a policy of default reminders (low and moderate quality evidence respectively). For people on TB prophylaxis: - More people attended the clinic with pre-appointment phone-calls, and the number attending the final clinic was higher with three-monthly phone-calls or nurse home visits. For people undergoing screening for TB: - Similar numbers of people attended clinic for skin test reading with and without pre-appointment phone-calls (low quality evidence). - Similar numbers of people attended clinic for skin test reading with and without take home reminder cards.
This review was undertaken to examine if single volume (removal of blood equivalent to the blood volume of the baby) is as effective as double volume (removal of twice blood volume of the baby) in reducing the brain damage and bilirubin levels in newborn infants with severe jaundice. Only one randomised trial fulfilled the criteria for inclusion in the analysis. This study compared single and double volume exchange transfusion in jaundice due to ABO hemolytic jaundice. The study found no significant difference in bilirubin levels following exchange. This study did not look at any long term neurodevelopmental outcome (brain damage). Based on the available data, there is insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns.
Twelve trials including 794 participants acute Achilles tendon rupture were included. The majority of participants were male, and the average ages of the study populations were between 36 to 41 years. Many of the trials had flawed methods that undermined the reliability of their results. Open surgical treatment compared with non-surgical treatment (6 studies, 502 participants) was associated with a lower risk of rerupture, but a higher risk of other complications such as infection, adhesions and disturbed skin sensibility (numbness and tingling). There were insufficient and inconclusive data on function and sporting activities. Percutaneous repair (involving stab incisions through which the repair suture is passed through without direct exposure of the tendon) compared with open repair (4 studies, 174 participants) was associated with a lower risk of infection. These figures should be interpreted with caution because of the small numbers involved. Similarly, no definitive conclusions could be made regarding different tendon repair techniques (3 studies, 141 participants).
We included 20 studies involving 1477 participants with COPD. Rehabilitation programmes started in hospital in some trials and after discharge in others. These programmes showed great diversity in terms of exercise training (e.g. number of completed exercise sessions, type and intensity of exercise training), patient education (none to extensive self-management programmes) and how programmes were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). Quality of life and exercise capacity were improved by rehabilitation, and the effect was substantially larger than the minimal important difference. Results for hospital readmissions and mortality were diverse, with some studies showing that pulmonary rehabilitation reduced hospital admissions and mortality compared with usual community care (no rehabilitation), and other studies not showing such effects. Uncertainty about reasons for differences across trials in terms of hospital readmissions and mortality led to downgrading of the quality of evidence (moderate-quality evidence for reduction in hospital readmissions and low-quality evidence for reduction in mortality). The quality of evidence was high for quality of life and exercise capacity. Pulmonary rehabilitation improves quality of life and exercise capacity and is a safe intervention for patients with COPD after they have experienced an exacerbation. The reasons for diverse effects on hospital readmissions and mortality, however, are not fully clear. Future studies should explore whether the extent of the rehabilitation programme and the organisation of such programmes within specific healthcare systems (e.g. within the rehabilitation setting vs embedded in the continuum of care from hospital to home to outpatient care) determines the effects of rehabilitation after COPD exacerbations.
Our review of seven randomised trials, involving 1396 women, found that intravenous or intramuscular magnesium sulphate was substantially better than intravenous diazepam in reducing the risk of maternal death and of having further seizures. Treatment was for 24 hours unless there was an indication to continue for longer. Diazepam infusion was titrated against the level of sedation, with the aim of keeping the woman drowsy but rousable.  Use of magnesium sulphate requires monitoring of respiration rate, tendon reflexes and urine output to avoid adverse effects. Fewer babies had low Apgar scores at birth with magnesium sulphate than with diazepam and, although admissions to a special care nursery were similar, fewer babies in the magnesium sulphate group had a length of stay of more than seven days. In other Cochrane reviews, magnesium sulphate was also substantially better than other drugs (phenytoin and lytic cocktail).
We found three studies for inclusion in the review. One recruited males with a biopsy-proven diagnosis of prostate cancer who were not receiving chemotherapy and had elected to receive external-beam radiation therapy; the second study recruited community-living participants who were aged 55 years and older; the third study recruited university students.These studies included people with anxiety or depression or both, and reported their results separately. This included only 25 people with anxiety, 17 with depression and 20 more with either anxiety or depression but which was not specified. The search is up to date as of 4 November 2014. Very few people with anxiety or depression or both have been included in randomised studies. This means there is insufficient evidence to make any comment about the usefulness of Reiki for the treatment of anxiety and depression. At best, the quality of the evidence is moderate which, on top of a dearth of evidence, weakens the findings further.
Cancer survivors often have many psychological and physical adverse events as a result of the cancer and treatment for it. They also suffer from poorer quality of life (QoL) than people without cancer. Some studies have suggested that exercise may be helpful in reducing negative outcomes and improving the QoL of people who have finished cancer treatment. Also, a better QoL may predict longer life. This review looked at the effect of exercise on QoL and areas of life that make up QoL (e.g. tiredness, anxiety, emotional health) among people who had finished all cancer treatment. The review included 40 trials with a total of 3694 people. The results suggest that exercise may improve overall QoL right after the exercise program is completed. Exercise may also reduce the person's worry about his or her cancer, and affect the way the person views his or her body.  Exercise may also help the way the person deals with emotions, sexuality, sleep problems, or functions in society.  Exercise also reduced anxiety, tiredness, and pain at different times during and after the exercise program.  No effect of exercise was found on the person’s ability to think clearly or his or her role function in society.  Also, no effect of exercise was found on the way the person views his or her spiritual or physical health, or physical ability. However, these findings need to be viewed with caution because this review looked at many different kinds of exercise programs, which varied by type of exercise, length of the program, and how hard the trial participants had to exercise. Also, the investigators used a number of different ways to measure QoL. More research is needed to see how to maintain the effects of exercise over a longer period of time after the exercise program is completed, and to determine which parts of the exercise program are necessary (i.e. when to start the program, type of exercise, length of program or exercise session, how hard to exercise). It is also important to find out if one type of exercise is better for a specific cancer type than another for the maximum effect on QoL.
We included four studies involving 3798 people with COPD. Most were men in their 60s who were moderate to heavy smokers. When they started treatment, they had moderate to severe symptoms of COPD. Studies ranged from three months to one year long. Studies were well designed and were funded by the drug manufacturer. Neither people in the study nor people doing the research knew which treatment participants were getting. People in the studies took either umeclidinium or placebo through an inhaler each morning. The conclusions of this review are current to April 2017. We determined the number of people who had a moderate flare-up. A moderate flare-up is treated with short-term oral steroids or antibiotics, or both. People who took umeclidinium were less likely than those given placebo to have a moderate flare-up. Eighteen people with COPD would need to be treated with umeclidinium to prevent one of these flare-ups. People taking umeclidinium probably had a better quality of life, and their lung function was better. People taking umeclidinium were less breathless and took fewer puffs of their reliever inhaler. Results showed little or no difference with umeclidinium in other outcomes, such as risk of dying during the study period, side effects, or the need to be admitted to hospital because of severe flare-ups. We are confident that umeclidinium inhalers are more likely than dummy inhalers to reduce moderate flare-ups and improve symptoms and lung function. However, we are less certain about effects of umeclidinium on quality of life, side effects, and serious side effects. We have limited confidence in terms of hospital admissions due to flare-ups, but this was a rare event. In people with COPD, umeclidinium inhalers improve symptoms, lung function, and quality of life compared with dummy inhalers. They also reduce the use of quick-relief medications and decrease flare-ups that need additional medication. However, no convincing evidence indicates that umeclidinium is better than dummy inhalers in terms of hospitalisations, side effects, serious side effects, or deaths.
The review found only two randomised trials, with only a limited number of patients. There was no consistent benefit from HBOT, but one trial did suggest an improvement in healing time. Overall, there is little evidence to support or refute the use of HBOT for burns patients. More research is needed.
In October 2017, we searched a list of literature databases and conference proceedings to identify studies that evaluated treatments for brain radionecrosis. A total of three studies were identified that evaluated drugs of which only two were RCTs and one of these RCTs had only 14 participants. No studies evaluating non-drug treatments were identified. The two drugs compared to corticosteroids alone in this review were bevacizumab (a drug affecting the blood vessels) and edaravone (a powerful antioxidant). A very small-sized study reported that bevacizumab improved the appearance of the radionecrosis on magnetic resonance imaging (MRI). This was associated with improvement in neurological symptoms than placebo but also with severe side effects. Edaravone in combination with corticosteroids improved the appearance of radionecrosis on MRI; this was associated with improvement in the reported symptoms using the LENT/SOMA scale. However, the patient and treating team were aware of the particular treatment the patient was receiving, so the reported symptoms may have been influenced by this. None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements. Finally a two arm non-randomised study of vitamin E versus no active treatment based on patient preference reported improvement in learning and memory, but this study did not report any imaging response. The results may have been influenced as patients chose their study treatment thus introducing other potential biases. Based on the findings of this review the certainty of the available evidence is low/very low, which limits our ability to help determine the risks and benefits of the evaluated treatments for brain radionecrosis. The studies were at risk of bias due to aspects of their study designs and/or very limited number of participants. There is a great need for higher-quality evidence with larger multi-centre randomised control trials of treatments for brain radionecrosis. In our search of the literature for this review, two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.
Seven randomised controlled trials conducted in the USA, UK, Canada and Australia related to a range of conditions and target populations. They provided some evidence of efficacy. Peer support telephone calls may increase mammography screening in women over 40 years, may help patients change their diet and cease smoking after a heart attack; and may help reduce depressive symptoms among mothers with postnatal depression. Findings need to be interpreted cautiously. There is a need for well designed randomised controlled studies to clarify which elements of peer telephone interventions work best to improve health and health-related behaviour.
Randomised controlled trials are the best types of studies to find out whether one treatment is better than another since it ensures that similar types of people receive the new and the old treatment. But we did not find randomised controlled trials; we identified six relevant non-randomised studies with a total of 334 patients, which compared laparoscopic and open surgeries. Since one of the studies did not provide usable results, five studies, with 326 patients, provided information for this review; laparoscopic surgery = 151 patients and open surgery = 175 patients. In four of these studies, historical information was collected from hospital records. In one study, new information was collected. In general, new information is considered to be more reliable than information from hospital records. The differences between laparoscopic and open transhiatal oesophagectomy were imprecise for: deaths during the short-term and long-term, the percentage of people with major complications, narrowing of the new junction between the gut, created after removing the oesophagus, cancer returning during the short-term and long-term, and the proportion of people who required blood transfusion. The proportion of patients with any complications and the average lengths of hospital stay were less in the key-hole group than the open cut group. There was lack of clarity about the difference in the amount of blood transfused between the two groups. None of the studies reported difficulty in swallowing after surgery, health-related quality of life, the amount of time it took to return to normal activity (same mobility as before surgery), or work. The quality of the evidence was very low. This was mainly because it was not clear whether participants who received laparoscopic surgery were similar to those who had open surgery. This makes the findings unreliable. Well-designed randomised controlled trials are necessary to obtain high-quality evidence on the best method to perform oesophagectomy.
This review of 32 studies (6597 women) looks at assisted or instrumental vaginal deliveries in women in the second stage of labour. The importance of this review is due to the fact that Instrumental delivery is a frequent intervention in childbirth and in some cases may result in harmful outcomes for either mother or baby or both. The main comparisons are between the forceps or the ventouse. There are also comparisons between different types of ventouse. The outcomes which are analysed are the success of the particular instrument in achieving the delivery and the rate of complications for both mother and baby. Not all studies considered all outcomes, and in particular, there were differences in the types of complications encountered by mothers and babies. In addition, we identified no studies for some comparisons. The results showed that the forceps was the better instrument in terms of achieving a successful delivery. However, it was also associated with higher rates of complications for the mother. These were perineal trauma, tears, requirements for pain relief and incontinence. There were risks of injury to the baby with both types of instrument. Comparisons between different types of ventouse revealed that the metal cup was better at achieving successful delivery than the soft cup,.but with more risk of injury to the baby. There were no significant differences between the handheld and the standard vacuum. Decisions as to which instrument is best will, therefore, depend upon individual situations where the urgency with which the baby needs to be delivered will be balanced against potential risks to the mother and baby.
Overall the five multi-centre randomised controlled trials (RCTs) recruited a total of 439 participants and between them compared different types of VNS therapy. Overall there were three randomised controlled trials which compared high frequency stimulation to low frequency stimulation in participants aged 12-60 years and another trial examined high frequency stimulation versus low frequency stimulation in children. Additionally, one trial examined three different stimulation frequencies. The review of these trials found that vagus nerve stimulation is effective, when used with one or more antiepileptic drugs, to reduce the number of seizures for people whose epilepsy does not respond to drugs alone. Common side effects were voice alteration and hoarseness, pain, shortness of breath, cough, feeling sickly, tingling sensation, headache or infection at the site of the operation, with shortness of breath, voice alteration and hoarseness more common in people receiving high frequency stimulation compared to people receiving low level stimulation. Out of the five included studies, two studies were rated individually as being of high quality and the other three studies were rated as being of unclear quality due to lack of reported information in the study paper about the methods of study design. The evidence for the effectiveness and side effects of VNS therapy was limited and imprecise from the small number of studies included in this review, so was rated as being of moderate to low quality. Further large, high quality studies are required to provide more information about the effectiveness and side effects of VNS therapy.
For this review, we searched the literature published up to April 2015 and found four studies that involved 450 participants which met our inclusion criteria. The included studies compared the proportions of fistulas that matured when evaluation was carried out before surgery using medical imaging techniques with standard care (no imaging). Our analysis found that vessel imaging before surgery did not improve the rate of fistulas that matured. Further research in this area involving more participants may be beneficial to better understand if imaging before surgery could help to increase the success of fistulas for people who need haemodialysis.
This review found that probiotics added to infant feeds may help prevent infant eczema, with one study suggesting the benefit may persist to four years of age. However, concerns regarding the quality of studies, inconsistency of findings between studies, and the fact that the benefits did not persist if restricted to infants with evidence of sensitisation to allergens, suggests that further studies are needed to confirm these results.
We found five studies that included 1254 patients who had this type of cardiac arrest in the prehospital setting. Four of the five studies (1186 patients) were well-designed studies with low risk of bias. Although no adverse events were reported, aminophylline showed no advantage when it was added to the standard resuscitation practice of paramedics when compared with placebo in these patients. It is not known whether giving aminophylline sooner would be helpful.
This review includes 14 randomised trials, involving 4596 operations, comparing the use of local anaesthetic to general anaesthetic for carotid endarterectomy. There was no statistically significant difference between the anaesthetic techniques in the percentage of patients who had a stroke or died within 30 days of surgery. This systematic review provides evidence to suggest that patients and surgeons can choose either anaesthetic technique, depending on the clinical situation and their own preferences.
In August 2012, did computer searches for randomized controlled trials of the quick-start method for pills and other hormonal birth control. We contacted researchers to find other studies. We included trials that compared quick start to the usual start of birth control. Also included were studies that compared quick start of different types of hormonal birth control with each other. Birth control methods could have the hormones estrogen and progestin (combined hormonal birth control) or just the progestin. Five studies were included. In a study of 'depo,' which is given as a shot, fewer women with quick start of depo became pregnant than those who used another method for 21 days before depo. In this review, the numbers of women who stopped using their birth control method early were similar between groups in all trials. In the depo trial, more women with quick start of depo were very satisfied. A trial of two quick-start methods showed women with the vaginal ring had less long-term bleeding and less frequent bleeding than those with pills. For six side effects, including changes in breasts, mood, and nausea, quick start of the ring showed fewer problems than quick start of pills. For satisfaction in that trial, more women in the ring group were very satisfied with their method of birth control. We found little evidence that quick start leads to fewer pregnancies or fewer women stopping early. However, fewer women on quick start of depo became pregnant than the women who started with another method. Other differences were between types of birth control rather than start times. Women using the vaginal ring had fewer problems than women using birth control pills. More studies are needed comparing quick start versus usual start of the same hormonal birth control method.
We searched for evidence up to 13 July 2018. We analysed data from two trials, one of which randomly allocated 65 people with drug-resistant tuberculosis to either a linezolid-containing or linezolid-free drug combination, and another that randomly allocated 39 participants to receive linezolid as part of their treatment from the start or have it added after a delay of two months. We also included 14 studies, including 1678 people, in which some participants received linezolid but others did not, but this was not determined at random. One trial showed a higher likelihood of cure and lower risk of treatment failure in participants receiving linezolid compared to those who did not. The second trial showed that participants who received linezolid immediately had a higher chance of tuberculosis being cleared from their sputum four months after the start of the study than those who added linezolid after a two-month delay. When they examined safety, the first trial found a higher risk of developing low red blood cell counts, nausea and vomiting, and nerve damage in people receiving linezolid. From 11 of the non-randomized studies that reported this, 22.6% of people had to stop linezolid due to adverse effects (side effects), though further comparisons of harmful effects were not possible due to incomplete reporting in the non-randomized studies. Overall, although there is some evidence of benefit, we have very low certainty in its accuracy. More high-quality studies are required before we can be certain how effective and safe linezolid is for drug-resistant tuberculosis. This review is current up to 13 July 2018.
This review concludes that immunoglobulins seem effective for preventing hepatitis A in both children and adults. However, the evidence, on which the conclusion is based, is not strong as the included trials appear to have risk of bias and their number is insufficient. Because there is a potential risk of blood-borne diseases from immunoglobulins preparations, such as human immunodeficiency virus, and because of the availability of hepatitis A vaccine, the use of immunoglobulins has become limited. However, their use is still required in some specific populations, such as persons with compromised immune function, children under one year of age, or persons who have not developed a full response to vaccine immunisation. Future clinical trials should address the benefit and harm of immunoglobulins in these populations.
We looked at previous Cochrane reviews on long-acting beta2-agonists and also searched for additional trials on long-acting beta2-agonists in children. We found a total of 21 trials involving 7318 children that provided information on the safety of formoterol or salmeterol given alone or combined with corticosteroids. We also found one trial on 156 children which directly compared formoterol to salmeterol. There were more non-fatal serious adverse events in children taking formoterol or salmeterol compared to those on placebo; for every 1000 children treated with formoterol or salmeterol over six months, 21 extra children suffered a non-fatal event in comparison with placebo. There was a smaller and non-significant increase in serious adverse events in children on formoterol or salmeterol and corticosteroids compared to corticosteroids alone: for every 1000 children treated with combination therapy over three months, three extra children suffered a non-fatal event in comparison with corticosteroids alone. This number illustrates the average difference between combination therapy and corticosteroids. Our analyses showed that in fact the true answer could be between 1 fewer and 12 more children who would experience a non-fatal event. We did not have enough numbers from the small trial comparing formoterol to salmeterol, or from information in the other trials, to tell whether one long-acting beta2-agonist treatment is safer than the other. There was only one death across all the trials, so we did not have enough information to tell whether formoterol or salmeterol increases the risk of death.
The authors reviewed all randomized studies comparing these drugs with placebo or with other analgesics and found that: local anesthetics were superior to placebo in decreasing intensity of neuropathic pain; limited data showed no difference in efficacy or adverse effects between local anesthetics and carbamazepine, amantadine, gabapentin or morphine; local anesthetics had more adverse effects than placebo; and local anesthetics were safe.
The purpose of this review was to assess the efficacy and safety of adding long-acting ß2-agonists to inhaled corticosteroids in asthmatic children and adults. Based on the identified randomised trials, in people who remain symptomatic while on inhaled corticosteroids, the addition of long-acting ß2-agonists improves lung function and reduces the risk of asthma exacerbations compared to ongoing treatment with a similar dose of inhaled corticosteroids alone in adults. We could not find evidence of increased serious adverse events or withdrawal rates due to adverse health events with the combination of long-acting ß2-agonists at usual doses and inhaled corticosteroids in adults. This provides some indirect evidence, but not total reassurance, regarding the short- and medium-term safety of this treatment strategy. There have not been enough children studied to assess the risks and benefits of adding LABAs in this age group.
We examined the evidence available up to 17 October 2014. We included 35 trials involving 13,872 adult participants, all of whom were randomized to either receive nitrous oxide or no nitrous oxide. The trials covered a variety of situations during general anaesthesia. We found that general anaesthesia with nitrous oxide increased the risk of pulmonary atelectasis (i.e. failure of the lungs to expand fully). When we restricted the results to the highest quality studies only, we found evidence that nitrous oxide may potentially increase the risk of pneumonia and severe nausea and vomiting. However, nitrous oxide had no effect on the patients' survival, the incidence of heart attack, stroke, wound infection, the occurrence of blood clots within veins, the length of hospital stay, or the length of intensive care unit stay. The evidence related to survival of participants was of moderate quality because we did not have enough data. The evidence related to some harmful effects, such as failure of the lungs to expand fully and heart attack, was of high quality, while for other harmful effects, such as stroke and the occurrence of blood clots within veins, the evidence was of moderate quality. For others, such as pneumonia, severe nausea and vomiting, and wound infection, the evidence was of low quality. The evidence related to the length of time spend in hospital was of moderate quality. The avoidance of nitrous oxide may be reasonable in participants with pre-existing poor pulmonary function or at high risk of postoperative nausea and vomiting.
Six trials providing information on the review question were identified. A total of 488 people with acute cholecystitis were included. Laparoscopic cholecystectomy was performed early (within seven days of people presenting to the doctor with symptoms) in 244 people while it was performed after at least six weeks in the remaining 244 people. The proportion of females ranged between 43.3% and 80% in the trials that provided this information. The average age of participants ranged between 40 years and 60 years. All the trials were at high risk of bias (and might have overestimated the benefits or underestimated the harms of either early laparoscopic cholecystectomy or delayed laparoscopic cholecystectomy). All the people included in the trials were discharged home alive after operation in the five trials from which this information was available. There was no significant difference in the proportion of people who developed bile duct injury, surgical complications, or who required conversion from key-hole to open operation between the two groups. None of the trials reported quality of life from the time of randomisation. The total hospital stay was shorter in the early group than the delayed group by four days. There was no significant difference in the operating time between the two groups. Only one trial reported the time taken for employed people to return to work. The people belonging to the early laparoscopic cholecystectomy group returned to work 11 days, on average, earlier than the delayed laparoscopic cholecystectomy group. Four trials did not report any gallstone-related complications during the waiting period. One trial reported five gallstone-related complications, including two people with cholangitis. There were no reports of pancreatitis during the waiting time. Gallstone-related morbidity was not reported in the remaining trial. Approximately one-sixth of people belonging to the delayed group had either non-resolution of symptoms or recurrence of symptoms before their planned operation and had to undergo emergency laparoscopic cholecystectomy in five trials. Based on information from a varied number of participants as well as trials at high risk of bias, early laparoscopic cholecystectomy during acute cholecystitis appears safe and shortens the total hospital stay. The majority of the important outcomes occurred rarely and hence one cannot rule out that future trials may show that one treatment or another may be better in terms of complications. However, the trial size required to show such differences involves a clinical trial on more than 50,000 people and so it is unlikely that such large trials will be performed. Several smaller randomised trials may answer the questions through meta-analyses.
We searched the literature published before 6 January 2014, and after assessment, included three small studies that involved 101 participants. Our analysis found that although CRRT showed limited advantages over conventional treatment to improve some aspects of kidney function and muscle tissue loss, we found no significant benefits in reducing risk of death. The small body of available evidence demonstrated poor methodological quality, and was insufficient to enable us to make any robust conclusions about the effectiveness of CRRT for people with rhabdomyolysis. Larger and better designed studies would be needed to investigate if CRRT is beneficial for people with rhabdomyolysis.
In this review, analysis of seven included studies with low risk of bias using G-CSF to improve the function of damaged heart of patient with heart attack failed to show any beneficial effects of this treatment. The rate of mortality was not different between the two groups (RR 0.64, 95% CI 0.15 to 2.80, P = 0.55). Also, left ventricular parameters including left ventricular ejection fraction (RR 3.41, 95% CI -0.61 to 7.44, P = 0.1), end systolic volume (RR -1.35, 95% CI -4.68 to 1.99, P = 0.43) and end diastolic volume (RR -4.08, 95% CI -8.28 to 0.12, P = 0.06) did not show significant changes between the treatment and the control groups. There was no evidence that the study was associated with serious adverse effects, however it should be noted that the study was limited since the trials included lacked long enough follow up durations. Additionally four studies had either high or unclear risk of bias for blinding. Therefore, based on the results of the current study, G-CSF treatment should not be administered for patients with heart attack.
There are many ways of performing a caesarean section and the techniques used depend on a number factors including the clinical situation and the preference of the operator. The peritoneum is a thin membrane of cells supported by a thin layer of connective tissue, and during caesarean section these peritoneal surfaces have to be cut through in order to reach the uterus and for the baby to be born. Following a caesarean section, it has been standard practice to close the peritoneum by stitching (suturing) the two layers of tissue that line the abdomen and cover the internal organs, to restore the anatomy. It has however been suggested that peritoneal adhesions may be more likely rather than less likely when the peritoneum is sutured, possibly as a result of a tissue reaction to the suture material. This review of trials sought to address whether to routinely suture these thin layers of tissue or not after delivering a baby by caesarean section. Twenty-nine randomised controlled trials were identified, with differences in their methodological quality; 21 trials involving over 17,000 women contributing data to the review. Several minutes were saved when the peritoneum was not stitched, and with a shorter period of hospital stay in most of the women. Postoperative adhesion formation was assessed in only four trials with 282 women, and no difference was found when leaving both layers of peritoneum unclosed was compared with closure of both. Longer-term outcomes were not adequately assessed, particularly adhesion formation, subfertility and ease of other surgeries in later life. Although the methodological quality of trials was variable, the results were in general consistent between the trials of better and poorer quality. Further studies are needed to further assess all these outcomes.
In this review, we asked how much do beta-blockers reduce BP when used as the second drug to treat hypertension. Twenty trials lasting an average of 7 weeks were found in the world scientific literature to answer this question. The data showed that the addition of a beta-blocker to thiazide diuretics or calcium channel blockers reduced BP by 8/6 mmHg when given at doses 2 times the recommended starting dose. When we compared these results with our previous review of the blood pressure lowering effect of thiazide diuretics as second line drug, we found that beta-blockers have a different pattern of BP lowering. This different pattern of effect on blood pressure might explain why first-line beta-blockers appear to be less effective at reducing adverse cardiovascular outcomes than first-line thiazide diuretics, particularly in older individuals.
The review included randomised controlled studies comparing the use of different interventions to improve dysphagia among patients with inoperable or unresectable primary oesophageal cancer. To find new studies for this updated review, in January 2014 we searched, according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases model, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL; and major conference proceedings (up to January 2014). The review updates the previous version but still fails to present any obvious superiority of one technique over another among the different kinds of interventions. Self-expanding metal stents provided safer and more effective relief of dysphagia compared to rigid plastic stents. Other techniques like radiotherapy or brachytherapy were also suitable alternatives and might be favourable in improving quality of life and prolonging survival. Individual differences should be emphasised when the intervention type was determined. Half of the studies included in this review were of high quality. Most studies did not state the methods used to seek and report quality of life outcomes and adverse effects.
Through February 2013, we did computer searches for randomized trials of ways to inform people about how well family planning methods prevent pregnancy. We wrote to researchers to find other trials. The new program could be compared to the usual practice or to another program or means of informing people. We found seven trials with a total of 4526 women. Two had several sessions for participants. One of those looked at the choice of birth control method. Women in the test program more often chose to be sterilized or to use modern birth control than women with the usual counseling. In the other study, the groups had different sessions on family planning. Both groups increased their birth control use. However, the groups were similar at six months in using methods that work well to prevent pregnancy. Five trials had a single session for each group. In one, women learned more from a slide-and-sound format than from having a doctor talk to them. Another trial found that effectiveness categories were better than pregnancy numbers for comparing the methods. Still another study provided structured counseling using a flipchart on family planning methods. The groups were similar in choice of birth control and in numbers who still used their chosen method at three months. The last study used videos to inform couples about family planning. The groups were mostly similar in birth control use after the videos. But those who watched videos on motivation and on family planning did not choose pills or an injectable method as often as those who watched only the family planning video. The studies had different types of participants and programs. We cannot say overall what would help consumers choose their method of birth control. Ways to inform women about family planning options should be tested in clinics. Trials should look at the choice of birth control method, along with how much consumers remember later.
Short or long-term health outcomes were not reported in any studies. We found very low quality evidence (the best evidence available currently) that there is no considerable difference in exposure between CSTD plus safe handling versus safe handling alone. We also found very low quality evidence (the best evidence available currently) that there is no considerable effect of CSTD on the percentage of surfaces contaminated and the amount of contamination in in pharmacy and patient-care areas for most drugs even though there was a small effect on contamination for one drug out of 24 studied and on amount of drug contamination for two drugs out of 15 studied . Therefore, no firm conclusions can be drawn on the effect of CSTD plus safe handling versus safe handling alone due to very low quality evidence available. Since most of the studies were conducted in pharmacy technicians and pharmacists and the CSTD used was PhaSeal, the evidence is applicable mainly to pharmacy technicians and pharmacists, and to PhaSeal. What was studied in the review? We included all types of studies that compared CSTD plus safe handling ('CSTD group') and safe handling alone ('control group'). What are the main results of the review? We included 24 studies (359 hospitals) in this review, none of which used the gold standard study design (randomised controlled trial) or explored a treatment's value for money. In 22 studies, the people who used the CSTD and safe handling were pharmacists or pharmacy technicians. Nineteen studies provide information that could be included for this study. No firm conclusion can be drawn on the effects of using CSTD on indirect measures of exposure such as the presence of the hazardous drug in the urine of the healthcare professionals or on the contamination of surfaces or the floor. There is significant variability between the studies in terms of whether the use of CSTD resulted in cost savings, with some studies reporting increased costs and others reporting decreased costs after introducing CSTD. None of the studies report on short or long-term health outcomes such as reduction in skin rashes, infertility, miscarriage, development of any type of cancer, or adverse events. We judged the certainty of evidence for all outcomes to be very low because all the studies had one or more significant limitations in their design. Therefore, the reported effects of interventions are uncertain. How up-to-date is this review? We searched for studies up until 26 October 2017.
This review could not provide evidence from randomised controlled trials that routine supplementation with vitamin B6 during pregnancy is of any benefit, other than one trial suggesting protection against dental decay. It may cause harm if too much is taken, as amounts well above the recommended daily allowance are associated with numbness and difficulty in walking. Vitamin B6 is a water-soluble vitamin which plays vital roles in numerous metabolic processes in the human body and helps with the development of the nervous system. Vitamin B6 is contained in many foods including meat, poultry, fish, vegetables, and bananas. It is thought that B6 may play a role in the prevention of pre-eclampsia, where the mother’s blood pressure is high with large amounts of protein in the urine or other organ dysfunction, and in babies being born too early (preterm birth). Vitamin B6 may be helpful for reducing nausea in pregnancy. This review of four trials (involving 1646 pregnant women) assessed routine B6 supplementation during pregnancy with the aim of reducing the chances of pre-eclampsia and preterm birth. Vitamin B6 as oral capsules or lozenges resulted in a decreased risk of dental decay in pregnant women in one trial. Lozenges had a greater effect, suggesting a local or topical effect of pyridoxine within the oral cavity. We did not find any clear differences in the risk of eclampsia or pre-eclampsia (three trials and two trials, respectively, low quality evidence). The studies did not have enough data to be able to make any other useful assessments. The included trials were conducted between 1960 and 1983 and did not include important newborn outcomes that have only recently been associated with vitamin B6, such as decreases in cardiovascular malformations and orofacial clefts. The trials began at different times during pregnancy, most had high rates of loss to follow-up, and adverse effects of vitamin B6 (pyridoxine) use were not assessed. Further research assessing outcomes such as orofacial clefts, cardiovascular malformations, neurological development, preterm birth, pre-eclampsia and adverse events would be helpful.
Five studies randomly assigned 762 women experiencing hot flushes/night sweats. Three trials and two trials, respectively, were included in pooled comparisons of exercise versus control (n = 454 women) and exercise versus yoga (n = 279 women). One small study (14 women) compared exercise versus hormone therapy. When exercise was compared with no intervention, no evidence was found of any difference in their effect on hot flushes. One small study suggested that HT is more effective than exercise. Evidence was insufficient to show whether exercise was more effective than yoga. None of the trials found any evidence of differences between groups with respect to adverse effects, but data were very scanty. The methodological quality of the studies was variable. We assessed the evidence as of low quality: The main limitations were poor reporting of study methods, inconsistent results and lack of precision.
Study characteristics: Four trials, in which a total of 1800 infants participated, examined whether giving VLBW infants a drug to prevent fungi growing on the skin or in the gut reduced the risk of bloodstream or other severe infection. The trials used one of two commonly available drugs (nystatin or miconazole) and compared these with either a placebo ("dummy" drug) or no drug. These trials, however, had some design weaknesses that make it less certain that their results can be taken at face value. Key results: The overall analysis suggested that this treatment might reduce severe infection rates in VLBW infants but there was no evidence of a reduction in the risk of dying. Conclusions: Larger and higher quality trials are needed to resolve this uncertainty.
The aim of this review was to assess the role of ischaemic preconditioning in liver resections performed utilising vascular occlusion. Four randomised clinical trials including 271 patients undergoing open liver resections fulfilled the inclusion criteria of this review. The patients were randomised to ischaemic preconditioning (n = 135) and no ischaemic preconditioning (n = 136) prior to continuous vascular occlusion. All the trials excluded cirrhotic patients. We assessed all the four trials as having high risk of bias (high risk of systematic error). There was no difference in mortality, liver failure, post-operative complications, hospital stay, intensive therapy unit stay, and operating time between the two groups. The proportion of patients requiring blood transfusion was lower in the ischaemic preconditioning group. The reasons for this are not clear. There was no difference in blood loss or enzyme markers of liver function between the two groups. The enzyme markers of liver injury were lower in the ischaemic preconditioning group on the first post-operative day. Currently, there is no evidence to suggest a protective effect of ischaemic preconditioning in non-cirrhotic patients undergoing liver resection under continuous vascular occlusion. Ischaemic preconditioning reduces the blood transfusion requirements in patients undergoing liver resection. Further high quality randomised clinical trials are necessary to assess the role of ischaemic preconditioning. Further studies are necessary to understand the mechanism of ischaemic preconditioning.
There were more treatment failures in women treated with an penicillin plus gentamicin (one study) compared with those treated with clindamycin plus gentamicin. Seven trials showed that an antibiotic treatment that had poor activity against bacteria resistant to penicillin had a higher failure rate and more wound infections than an antibiotic treatment that had good activity against these bacteria. There was no evidence that any of the antibiotic combinations had fewer adverse effects - including allergic reaction - than other antibiotic combinations. If the endometritis was uncomplicated and improved with intravenous antibiotics, there did not appear to be a need to follow the intravenous antibiotics with a course of oral antibiotics. Overall the reliability of the studies' results was unclear, the numbers of women studied were often small and data on other outcomes were limited; furthermore, a number of the studies had been funded by drug companies that conceivably would have had a vested interest in the results.
After extensive searching to find relevant studies, we found only two randomised controlled trials (RCTs) that were eligible for this review (RCTs provide more robust results than other trial types). The studies were small with a total of 64 participants randomised, all over 18 years of age, with a perianal abscess. In the studies, participants received either packing by community nursing teams or no packing. Participants in the non-packing group managed their own wounds by using absorbant dressings to cover the area with no internal dressing. Participants were seen fortnightly until the cavity had healed. It is not clear whether time to complete wound healing is affected by packing of cavity (and what evidence exists is very low quality). There was very low quality evidence that packing made no difference to wound pain at the first dressing change. There was very low quality evidence that on judging the wound pain over the preceding two weeks, participants in the packing group had experienced more pain that those in the non-packing group. It is not clear whether packing or not affects the number of post-operative fistulae or abscess recurrences. We did not find any RCTs that compared participant health-related quality of life/health status, incontinence rates, time to return to work or normal function, resource use in terms of number of dressing changes or visits to a nurse, or change in wound size. There is no high quality evidence for the use of packing for healing perianal abscess cavities. Assessed as up to date to 17th May 2016.
We included three small studies (with a total of 154 infants) that compared the effects of feeding supplementation with prebiotics on neonatal jaundice to a placebo (such as distilled water). The evidence is up to date as of 14 June 2018. There is inadequate evidence to assess the effectiveness of prebiotics on neonatal jaundice. According to the available data, the incidence of neonatal hyperbilirubinaemia (low-quality evidence) and treatment with phototherapy (low-quality evidence) were decreased by feeding supplementation with prebiotics, but only one small study reported on these outcomes. The meta-analyses of these small studies demonstrated a significant reduction in the length of hospital stay (low-quality evidence) and a significant increase in stool frequency (high-quality evidence) in infants with prebiotic supplementation versus placebo. Furthermore, meta-analyses showed no significant difference in maximum plasma bilirubin levels (low-quality evidence), duration of phototherapy (low-quality evidence) and neonatal mortality (low-quality evidence) between groups. The review found only three randomised clinical trials that compared prebiotic supplementation with a placebo. More research is needed.
This review includes evidence up to 11 August 2015. We included two randomised controlled trials with a total of 78 participants. One trial involved 30 adults with nasal polyps. Participants received either intranasal corticosteroids and oral corticosteroids or only intranasal corticosteroids. The only result reported of interest to this review was whether the size of the nasal polyps was reduced, when these treatments were completed (three weeks). One trial involved 48 children (mean age of eight years) with chronic rhinosinusitis but no nasal polyps. Participants received either antibiotics and oral corticosteroids or only antibiotics and a placebo (sugar pill). The oral corticosteroids and placebo were given for 15 days and the antibiotics were given for 30 days. The trial reported findings when the antibiotic treatment was completed (at one month). At the end of a three-week treatment course, people who took both intranasal corticosteroids and oral steroids may have had smaller nasal polyps than people who just received intranasal corticosteroids. The trial did not follow up people to determine whether the polyp size increased after the end of the trial. The trial did not provide information on adverse events or other outcomes important to patients, such as symptom severity or quality of life. Children who received both antibiotics and oral corticosteroids seemed to have a lower total symptom score and better computerised tomography (CT) scan score after treatment compared with children who received antibiotics and control treatment. The reporting of adverse effects in this trial was not very clear and so is difficult to tell if any participant experienced gastrointestinal disturbances, mood changes or difficulty in sleeping. We judged the quality of the evidence for oral steroids plus intranasal steroids for adults with nasal polyps to be very low (we are very uncertain about the estimate) as the evidence comes from one trial that has a low number of participants. The trial had a high risk of bias due to the way it was conducted. The trial did not report adverse events and did not report results after the end of treatment. We judged the quality of the evidence for oral steroids plus antibiotics for children to be low (further research is very likely to have an important impact on our confidence in the effect estimate and is likely to change the estimate) as the evidence comes from one small trial. The trial did not have a high risk of bias, but it only included children without nasal polyps, who might not have the same results as adults with nasal polyps. The trial did not report results after the end of treatment and the adverse effects of treatment were not well reported.
We included a total of three trials involving 209 participants who were treated with oral zinc pills or placebo. All patients were adults over 18 years who had subjective tinnitus. All three studies investigated improvement in tinnitus as their primary outcome. One study assessed adverse effects and our secondary outcome 'change in overall severity of tinnitus'. Two studies assessed tinnitus loudness. Only one study, which enrolled only elderly patients, used a validated instrument (the Tinnitus Handicap Questionnaire (THQ)) to measure the primary outcome. The other two studies measured tinnitus using scales (from 0 to 7 and from 0 to 10), but these scales were not validated instruments for studying tinnitus. All three included studies had differences in their participant selection, length of follow-up and outcome measurement, which prevented a meta-analysis (combining of results). Only one trial (conducted in 2013) used a validated instrument (the THQ) to measure improvement in tinnitus, our primary outcome. The authors reported no significant difference between the groups. Another study (2003) reported the severity of tinnitus using a non-validated scale (0 to 7) and found a significant difference in the subjective tinnitus scores, which favoured the zinc group. However, this result may be biased because the losses were unbalanced and higher in the placebo group. A third study (1991) also evaluated improvement of tinnitus using a non-validated instrument (a scale of 0 to 10) and found no significant difference between groups. There were no severe adverse effects associated with zinc. Three cases of mild adverse effects were reported in different participants (e.g. mild gastric symptoms). Two studies (2003 and 2013) assessed change in tinnitus loudness (one of our secondary outcomes), but did not find a difference between patients treated with zinc compared to those who took a placebo. Two studies assessed change in the overall severity of tinnitus. One study, published in 1991, did not find any difference for this outcome between the groups. The second study, published in 2003, reported a significant reduction in subjective tinnitus score in the zinc group and no difference in the placebo group. However, both studies used a non-validated scale. The quality of the evidence is very low. We found no evidence that the use of oral zinc supplementation improves symptoms in adults with tinnitus. This evidence is up to date to 14 July 2016.
The authors found 75 studies investigating the effectiveness of cell salvage in orthopaedic (36 studies), cardiac (33 studies), and vascular (6 studies) surgery. Overall, the findings show that cell salvage reduces the need for transfusions of donated blood. The authors conclude that there appears to be sufficient evidence to support the use of cell salvage in cardiac and orthopaedic surgery. Cell salvage does not appear to cause any adverse clinical outcomes. As the methodological quality of the trials was poor, the findings may be biased in favour of cell salvage. Large trials of high methodological quality that assess the relative effectiveness, safety, and cost-effectiveness of cell salvage in different surgical procedures should be the focus of future research in this area.
We searched nine databases for articles evaluating standardised packaging that had been already reviewed by academics and published before January 2016. We also checked references in those papers to other studies and contacted the authors where necessary. We found 51 studies involving approximately 800,000 participants. These studies varied considerably. Some studies focused on the effect of standardised packaging in Australia, and included looking at overall smoking levels, whether smokers altered their behaviour such as by cutting down the number of cigarettes they smoked, and whether smokers were making more quit attempts. We also included experiments in which people used or viewed standardised tobacco packs and examined their responses, compared to when they were viewing branded packs. We also included studies that assessed people’s eye movements when they looked at different packs and how willing people were to buy, and how much they were willing to pay for, standardised compared to branded packs. Only five studies looked at our key outcomes. One study in Australia looked at data from 700,000 people before and after standardised packaging was introduced. This study found that there was a half a percentage point drop in the proportion of people who used tobacco after the introduction of standardised packaging, compared to before, when adjusting for other factors which could affect this. Four other studies looked at whether current smokers changed the number of cigarettes they smoked. Two studies from Australia looked at this, one using surveys which included 8811 current smokers, and found no change in the number of cigarettes smoked. The three smaller studies found mixed results. Two further studies looked at quit attempts and observed increases in these in Australia after standardised packaging was introduced. The remainder of the studies looked at other outcomes, and the most consistent finding was that standardised packaging reduced how appealing people found the packs compared with branded packs. No studies reported the number of people who quit using tobacco, the number of people who started using tobacco, or the number of people who returned to using tobacco after quitting. Certainty in these findings is limited for several reasons, including the difficulties involved in studying national policies like standardised packaging. However, findings suggesting standardised packaging may decrease tobacco use are supported by routine data from the Australian government and studies looking at other outcomes. For example, in our included studies people consistently found standardised packs less appealing than branded packs. We did not find any evidence suggesting standardised packaging may increase tobacco use.
In this systematic review of randomised controlled trials four studies were reviewed. Three studies involving 498 participants compared subcutaneous lignocaine, a short-acting local anaesthetic, with a control group (participants received either no pain relief or an inactive substance known as a placebo). Two studies involving 399 people compared intravenous opioids (fentanyl or morphine) and an anxiolytic (midazolam) with a control group. One study involving 60 people compared subcutaneous levobupivacaine, a long-acting local anaesthetic, with a control group. Intravenous pain regimens and subcutaneous levobupivacaine appear to reduce the pain experienced during femoral sheath removal. However, the size of the reduction was small. A significant reduction in pain was not experienced by participants who received subcutaneous lignocaine or who were in the control group. There were insufficient data to determine a correlation between pain relief administration and either adverse events or complications. Some patients may benefit from routine pain relief using levobupivacaine or intravenous pain regimens. Identifying who may potentially benefit from pain relief requires clinical judgement and consideration of patient preference. The mild level of pain generally experienced during this procedure should not influence the decision as some people can experience moderate levels of pain with the conventional wound care.
We looked for randomized controlled trials which compared different types of IPC devices for preventing venous thromboembolism in patients after THR. We found one study with 121 participants comparing a calf-thigh compression device with a foot (plantar) compression device. There were no cases of symptomatic DVT or PE either in the calf-thigh compression group or the plantar compression group in the first three weeks after the THR. The calf-thigh pneumatic compression was more effective than plantar compression for reducing thigh swelling one week following surgery. The postoperative swelling in the calf-thigh pump group was reduced earlier than in the plantar pump group. However, other outcomes such as imaging-diagnosed asymptomatic VTE were not determined and it is not possible to draw reliable conclusions from this single study with a high risk of bias. We therefore suggest that more primary research is required to allow an informed choice of IPC device for preventing venous thromboembolism following THR.
This review found that the amount of blood loss was clearly reduced when a tourniquet was used during surgery for varicose veins, with no overall increase in operative time, reported adverse events or change in patient reported pain and activity after surgery. Three trials were included in the review, in which a total of 176 men and women (211 legs) were randomised to either use or non-use of a tourniquet. All trials took place in the UK between 1989 and 2000. Those patients who did not have a tourniquet had a wider range of total blood loss and patients in the upper limits lost a significant amount of blood. A reduction in blood loss may also result in a reduction in post-operative bruising but only one of the trials (50 patients) looked at this. It found a clear reduction in the area of bruising with the use of a tourniquet. The trials did not have a large enough number of participants to determine any rarer complications of surgery with the use of a tourniquet such as nerve damage or arterial injury, especially in older patients.
Evidence from 121 randomised controlled trials (6,700 participants) shows that older people who exercise their muscles against a force or resistance become stronger. They also improve their performance of simple activities such as walking, climbing steps, or standing up from a chair more quickly. The improvement in activities such as getting out of a chair or stair climbing is generally greater than walking speed. Moreover, these strength training exercises also improved older people's physical abilities, including more complex daily activities such as bathing or preparing a meal. PRT also reduced pain in people with osteoarthritis. There was insufficient evidence to comment on the risks of PRT or long term effects.
This review of trials suggests that exercise has positive short-term effects on self-esteem in children and young people, and concludes that exercise may be an important measure in improving children's self-esteem. However, the reviewers note that the trials included in the review were small-scale, and recognise the need for further well-designed research in this area.
We searched for studies comparing giving versus not giving empiric antibiotics or comparing different antibiotics in those with suspected meningococcal disease. We found one randomised trial comparing single intramuscular doses of two different long-acting antibiotics. The evidence is current to January 2017. The included study was conducted in nine primary care facilities in Niger during an outbreak of meningococcal disease in 2003. Of 510 adults and children studied, 251 received ceftriaxone and 259 received chloramphenicol. The study was funded by Médecins Sans Frontières. There was no difference in the number of people who died, did not respond to treatment, or with neurological disabilities with either antibiotic empirically. The results were similar in whom the diagnosis was subsequently confirmed. Neither antibiotic had significant adverse effects. Although the study was well conducted, the overall quality of the evidence was only moderate for death and treatment failures because the study excluded children less than two months old, pregnant women, and the severely ill. The quality of evidence was lower for neurological disabilities because of the shortness of follow-up. Since meningococcal disease has serious consequences, not giving antibiotics empirically would be unethical. However, future research comparing different antibiotics in people of all ages and illness severity is required to provide reliable evidence in different clinical settings.
The purpose of this review was to look at whether home-based parenting programmes, which aim to improve child development by showing parents how to provide a better quality home environment for their child, are effective in doing so. Seven randomised controlled trials (RCTs) met the inclusion criteria for this review. It was possible to combine the results from four of the seven studies, which showed that children who received the programme did not have better cognitive development than a control group. Socioemotional development was measured in three studies but we could not combine this data to help reach a conclusion about effectiveness. None of the studies measured adverse effects. The quality of the evidence in the studies was difficult to assess due to poor reporting. More high quality research is needed.
Irrespective of the type or combination of anticoagulant, no benefit of anticoagulant treatment was found for live births. Obstetric complications were not clearly affected by any treatment regimen. Injection of low molecular weight heparin caused local skin reactions (pain, itching, swelling) in one study (side effects were not regularly reported in all studies). In the nine reviewed studies quality varied and different treatments were studied. Three studies were considered at high risk of bias. The number of studies on this topic remains limited. Thrombophilia refers to blood clotting disorders associated with a predisposition to thrombosis and thus increased risk for thrombotic events. It can be inherited as well as acquired, as is the case in the antiphospholipid syndrome. Both inherited and acquired thrombophilia are associated with vascular thrombosis as well as pregnancy complications including recurrent miscarriage and premature delivery.
We identified 19 randomised clinical trials in this review. Most participants in the trials were low anaesthetic risk people undergoing planned laparoscopic cholecystectomy. A total of 1095 participants were randomised to local anaesthetic wound infiltration (587 participants) or no local anaesthetic wound infiltration (508 participants) in 17 trials. The choice of whether the participants received local anaesthetic agents (or not) was determined by a method similar to the toss of a coin so that the treatments were compared in groups of patients who were as similar as possible. There were no deaths in either group in the seven trials (539 participants) that reported deaths. The difference in serious complications between the groups was imprecise. There were no local anaesthetic-related complications in nearly 450 participants who received local anaesthetic wound infiltration in the different trials that reported complications. None of the trials reported quality of life or the time taken to return to work. The proportion of participants who were discharged as day surgery patients was higher in the local anaesthetic group than in the control group in the only trial that reported this information. The difference in the length of hospital stay or the time taken to return to normal activity was imprecise. Pain was lower in the participants who received intra-abdominal local anaesthetic administration compared with those in the control groups at four to eight hours and at nine to 24 hours, as measured by the visual analogue scale (a chart which rates the amount of pain on a scale of 1 to 10). In the comparisons of different methods of local anaesthetic infiltration, there were differences between the groups in some outcomes but the changes were not consistent. There is, therefore, no evidence to prefer any particular drug or method of administering local anaesthetics. Serious adverse events were rare in studies evaluating local anaesthetic wound infiltration. There is very low quality evidence that infiltration reduces pain in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the clinical importance of this reduction in pain is likely to be small. Most of the trials were at high risk of bias, that is there is a possibility of arriving at wrong conclusions by overestimating the benefits or underestimating the harms of one method over another because of the way a study was conducted. The overall quality of evidence was very low. Further trials are necessary. Such trials should include outcomes such as quality of life, hospital stay, the time taken to return to normal activity, and the time taken to return to work, which are important for the person undergoing laparoscopic cholecystectomy and the people who provide funds for the treatment.
This review looked at trials of inhaled epinephrine for the treatment of children with croup and is comprised of only eight studies with 225 participants. Of the eight included studies, six were assessed as having low risk of bias and two as unclear risk of bias (based upon assessment of adequate random sequence generation, allocations concealment, blinding of participants and personnel, blinding of outcome assessment, completeness of outcome data, and selective reporting). Studies assessed a variety of outcome measures and few studies examined the same outcomes; therefore, most outcomes contained data from a maximum of three studies, and in some cases only single studies. Compared to no medication, inhaled epinephrine improved croup symptoms in children at 30 minutes following treatment (three studies, 94 children). This treatment effect disappeared two hours after treatment (one study, 20 children). However, children's symptoms did not become worse than prior to treatment. No study measured adverse events. The evidence is current to July 2013.
Our review identified five randomised controlled trials with a total of 303 to 305 participants who suffered from tinnitus. These studies compared participants receiving betahistine to those receiving a placebo. Four study designs allocated participants into parallel groups. In one study, participants consented to take all study medications in a pre-defined sequence. The outcomes that we evaluated included tinnitus loudness and intrusiveness, tinnitus symptoms and side effects. The included studies did not show differences in tinnitus loudness, severity of tinnitus symptoms or side effects between participants receiving betahistine and participants receiving a placebo. No significant side effects were reported. We had planned to evaluate changes in tinnitus intrusiveness, depression and anxiety and quality of life, but these were not measured. The evidence suggests that betahistine is generally well tolerated with a similar risk of side effects to placebo. The quality of the evidence ranged from moderate to very low. The risk of bias in all of the included studies was unclear. The results were drawn from one or two studies only. In some studies, the participants that were included did not fully represent the entire population of people with tinnitus and so we cannot draw general conclusions.
Whereas not all single studies demonstrated a survival benefit for patients treated with interferon, combining the available evidence, we found that the use of postoperative interferon improves the survival of those with high-risk melanoma. On average, the toxicity associated with interferon administration (such as fever and fatigue) is limited; moreover, it is reversible when the treatment is stopped. Since interferon alpha is the only approved drug after surgery for those with high-risk melanoma, efforts to identify those who might benefit most from this treatment are very important in order to avoid unnecessary toxicity for those who would not benefit from interferon alpha treatment. Combination of interferon with novel drugs is another field of ongoing research to improve the life expectancy of people with high-risk melanoma.
We found 73 randomised controlled trials comparing GnRH antagonist with GnRH agonist in a total of 12,212 women undergoing ART. The evidence is current to May 2015 There was no evidence of a difference between the groups in live birth rates (i.e. rates at conclusion of a course of treatment). The evidence suggested that if the chance of live birth following GnRH agonist is assumed to be 29%, the chance following GnRH antagonist would be between 25% and 33%. However, the OHSS rates were much higher after GnRH agonist. The evidence suggested that if the risk of OHSS following GnRH agonist is assumed to be 11%, the risk following GnRH antagonist would be between 6% and 9%. The evidence was of moderate quality for both live birth and OHSS. The main limitations of the evidence were the possibility of publication bias for live birth (with small studies likely to report favourable outcomes for GnRH antagonist) and poor reporting of study methods for OHSS.
We found 15 studies that included 498 participants. Ten studies compared physical activity to minimal dietary and behavioural intervention or no intervention. Five studies compared combined dietary, exercise and behavioural intervention to minimal intervention. One study compared behavioural intervention to minimal intervention. The risk of bias in the studies varied and was generally unclear. The evidence is current to March 2018. There were no studies that investigated the effect of a healthy lifestyle on live birth, miscarriage or regularity of menstrual cycles. Adopting a healthy lifestyle may result in weight loss or reduction in male hormone levels in some individuals. Diet and exercise may not have an effect on the body's ability to maintain normal blood glucose levels. The evidence was of low quality. The main limitations in the evidence were inconsistent and imprecise findings, and poor reporting of the methods used in the studies.
The review authors searched the medical literature up to January 2014, and identified 10 relevant medical trials, with a total of 422 participants. Nine of these studies were on people having rhinoplasty (surgery to reshape the nose) and one was on people having a facelift.The trials investigated a variety of corticosteroid medicines, as well as different doses of corticosteroids. People in the studies were assessed for swelling and bruising for up to 10 days after surgery. None of the studies stated the funding source. There was some low quality evidence that a single dose of corticosteroid administered prior to surgery might reduce swelling and bruising over the first two days after surgery, but this advantage was not maintained beyond two days. One study, with 40 participants, showed that high doses of corticosteroid decreased both swelling and bruising between the first and seventh postoperative days. The usefulness of these results is uncertain and there is currently no evidence regarding the safety of the treatment. Five trials did not report on harmful (adverse) effects; four trials reported that there were no adverse effects; and one trial reported adverse effects in two participants treated with corticosteroids as well as in four participants treated with placebo. None of the studies reported recovery time, patient satisfaction or quality of life. Therefore, the current evidence does not support use of corticosteroids as a routine treatment in facial plastic surgery. More trials will need to be conducted before it can be established whether this treatment works and is safe.
Although we included 17 trials, involving 3212 patients, in this review, the risk of bias was so high that the evidence did not support using any Chinese herbal preparation(s) for the common cold. Well-designed clinical trials are required.
In the USA there is growing public enthusiasm for DHEA supplementation as a means of retarding ageing and age-associated cognitive impairment but there is very little evidence from controlled trials. In two trials DHEA was associated with a deleterious effect on visual memory after a psychosocial stressor and quality of life measures, but there is inconsistent systematic evidence of adverse effects from DHEA. Longer-term randomized placebo controlled trials are needed for low and high doses.
It is not clear whether medication or surgery is the better treatment for OAG. The purpose of this review was to review and assess evidence from randomised studies to compare treatment with medications with surgical treatments in terms of how well they work, their relative safety and cost-effectiveness. Four relevant trials were identified, treating 888 people. Three studies were in the UK and one in the US. These trials had been initiated over many years from 1968 up to the most recent trial in 1993. The earlier trials used medications, and in one trial surgical techniques that are now rarely used. Findings of these studies suggest that, in mild OAG, worsening of the condition was not different whether first treatment was medication or surgery, but surgery was associated with more eye discomfort at five years. In more severe glaucoma, surgery lowered IOP significantly more than medications (not widely used anymore) and reduced the risk of progressive loss of visual field. In three trials the risk of developing cataract was higher with surgery (trabeculectomy), although in one trial with follow-up beyond five years there was no difference in the number of cataract surgeries between treatment groups. There was insufficient evidence to determine how well more recently available medications work compared with surgery in more severe OAG, and which was the more cost-effective treatment option. More research is required.
We performed a thorough search of the medical literature up to June 2014. We identified 13 trials that recruited 7310 participants. Two trials recruited healthy participants and the other 11 trials recruited people at varying risk of CVD, such as participants with known hypertension("high blood pressure") and type 2 diabetes, and randomly assigned them to either a multiple risk factor intervention or to no intervention. The trials were conducted between 2001 and 2010, and published between 2004 and 2012. Three trials were conducted in Turkey. Two trials each were conducted in China and Mexico. One trial recruited participants from both China and Nigeria. The other trials were conducted in Brazil, India, Pakistan, Romania and Jordan. The content of the interventions varied across the trials; most of the trials included dietary advice and advice on physical activity. The trials follow-up the participants between six months to 30 months (average follow-up period was 13.3 months). We found that evidence for effects on cardiovascular disease events was scarce, with only one trial reporting these. None of the included trials reported deaths from any cause. Multiple risk factors interventions may lower systolic blood pressure, diastolic blood pressure, body mass index and waist circumference. We found no difference for eating more fruit and vegetables, rates of smoking cessation, measure of blood glucose sugar was for the past two to three months, fasting blood sugar, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and total cholesterol. None of the included trials reported on harms. Overall, the studies included in this review were at some risk of bias and there was variation between the results of the studies when we analysed the data. Our findings should be treated with some caution.
This review was conducted to find out if combining doxorubicin with other drugs is more effective than doxorubicin alone. Eight studies were considered together, which showed if combination chemotherapy is given: (1) tumour shrinkage was marginally better than in patients treated with doxorubicin alone; (2) survival was no different; and (3) side effects were worse than for patients treated with doxorubicin alone
Twenty-one trials (with over 2000 participants) were included. Paracetamol provided a statistically significant benefit when compared with placebo for pain relief at both 4 and 6 hours after taking the drug. It is most effective at 1000 mg dose, and can be taken at six hourly intervals without compromising safety. There was no statistically significant difference between the number of patients who reported adverse events, overall this being 19% in the paracetamol group and 16% in the placebo group. It should be noted that most of the studies were found to have some limitations mainly due to poor reporting of information. However the review concludes that paracetamol is a safe, effective drug for the treatment of postoperative pain following the surgical removal of lower wisdom teeth.
In September 2016 we searched for as many relevant studies as we could find that had a reliable design (randomised controlled trials) and had compared PMM treatments with other treatments for venous leg ulcers. We found 12 studies involving a total of 784 people. Ten studies gave results we could use and all treatments were dressings. All these studies gave all the participants compression therapy as well as the dressings. Most of the people in the trials had wounds that were not getting better or had been there a long time. Findings from four trials are unclear as to whether there is a benefit of PMM dressings on venous ulcer healing compared with other dressings. Five trials reported on wound side effects and their results are unclear as to whether there is a difference in rates of side effects between PMM dressings and other dressings. It is also unclear whether PMM dressings result in decreases in the amount of saline used and the time taken during dressing changes, and whether there is an effect on total costs. Overall, the certainty of the evidence was judged to be low: most studies we found were small and could have been better conducted, so it was difficult to be sure how meaningful the results were. The next step would be to do more research of better quality to see whether PMM dressings do heal venous ulcers more quickly than other dressings. This plain language summary is up to date as of September 2016.
The review only included randomized controlled trials, studies in which a group of babies received massage and was compared with a similar group which did not. The authors searched the medical literature and contacted experts and found 14 studies. In most of these studies babies were rubbed or stroked for about 15 minutes, three or four times a day, usually for five or ten days. Some studies also included "still, gentle touch", in which nurses put their hands on babies but did not rub or stroke them. On average, the studies found that when compared to babies who were not touched, babies receiving massage, but not "still, gentle touch", gained more weight each day (about 5 grams). They spent less time in hospital, had slightly better scores on developmental tests and had slightly fewer postnatal complications, although there were problems with how reliable these findings are. The studies did not show any negative effects of massage. Massage is time consuming for nurses to provide, but parents can perform massage without extensive training.
We found 53 trials consisting of 1139 participants. Forty-eight studies used a cross-over design, which meant that each person in the trial received two or more treatments－one or more active treatments, the beta-agonist and a placebo in random order. The rest were parallel-group trials, meaning that people received either the active treatment or a placebo. Most of the studies addressed the effect of a giving a single beta2-agonist treatment before exercise and recorded the effect on lung function following exercise. Only eight focused on longer treatment－longer treatments would be needed to assess whether these treatments were harmful over the longer term. Studies in which people received a single administration of a beta-agonist showed that FEV1 (a measure of lung function) fell significantly less for people taking SABA or LABA compared with placebo (mean difference (MD) -17.67%; 95% confidence interval (CI) -19.51% to -15.84%). Other lung function measures confirmed that beta2-agonists were more beneficial compared with placebo. No significant difference in the number of side effects was noted in people taking SABA or LABA compared with people taking placebo. However, it is unlikely that people would be prescribed an inhaler for a single treatment, so we must consider longer-term studies to get a true measure of the side effects that inhalers can cause. We found that included longer-term studies showed that beta2-agonists were helpful in terms of lung function for the first dose of treatment. However, studies that provided longer-term treatment with SABA or LABA showed that over time, people built up a tolerance to the effects of treatments, and the beneficial effects lasted for shorter periods of time. Overall, we believe that the evidence was of low to moderate quality. This review shows that beta2-agonists－both SABA and LABA－when administered in a single dose, are effective and safe in preventing the symptoms of EIA. Longer-term administration of inhaled beta2-agonists induces tolerance and lacks sufficient safety data. It is important to note that taking LABA without background inhaled steroids is considered unsafe and is not currently recommended in most of the clinical guidelines for asthma. We recommend that more studies are needed to determine whether it is safe to administer inhaled beta2-agonists alone to people who experience asthma symptoms when exercising. This review is current as of August 2013.
Review authors searched the medical literature up to 10 September 2018, and identified five relevant randomised clinical trials, including a total of 398 participants. All trials were performed in Italy by only one team of investigators. All were considered at high risk of bias and included small numbers of participants, which makes potential overestimation of benefits and underestimation of harms likely. The pharmaceutical industry did not sponsor any trial. Trials tested acetyl-L-carnitine given orally or intravenously versus placebo. The drug did not seem to have effects on quality of life, fatigue, or non-serious adverse events when compared with placebo (inactive sham drug). None of the included trials reported data on participants’ all-cause mortality, serious adverse events, or days of hospitalisation. Researchers poorly reported harms caused by acetyl-L-carnitine, so the harms profile remains unclear. Risks of bias, imprecision, and outcome reporting bias all make the certainty of evidence low or very low. A reduction in blood ammonium levels favoured participants receiving acetyl-L-carnitine, but study authors observed no clinical benefits. It is clear that additional randomised clinical trials are required to assess the benefits and harms of acetyl-L-carnitine compared with placebo in the treatment of people with hepatic encephalopathy. These trials should be well designed, conducted by independent researchers, and collaborative, and should include large numbers of participants.
The review included nine randomised controlled trials involving a total of 816 women who were randomised to receive metformin (411) versus placebo or no treatment (405). The trials were conducted in the Czech Republic, Italy, Jordan, Norway, Turkey and the United Kingdom. The evidence is current to October 2014. When metformin was compared with placebo or no treatment, there was no conclusive evidence of a difference between the groups in live birth rates, but pregnancy rates were higher in the metformin group, and the risk of OHSS was lower. We estimated that for a woman with a 32 % chance of achieving a live birth using placebo, the corresponding chance using metformin would be between 28% and 53%. For a woman with a 31% chance of achieving a clinical pregnancy without metformin, the corresponding chance using metformin would be between 32% and 49%. For a woman with a 27% risk of ovarian hyperstimulation syndrome (OHSS) without metformin, the corresponding chance using metformin would be between 6% and 15%. Side effects (mostly gastrointestinal) were more common in the metformin group, though only four studies reported this outcome. The overall quality of the evidence was moderate for the outcomes of clinical pregnancy, OHSS and miscarriage, and low for other outcomes. The main limitations in the evidence were imprecision and inconsistency. We found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS. However, the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS.
The review included two trials (up to August 2015) conducted in Spain and the USA, involving 1284 people with cataract. A total of 68 people were treated as day care surgery, while 598 stayed overnight in the hospital. The mean age of the participants was about 70 years and there were slightly more women than men. The studies were not funded by a drug company. The two studies in this review found that in developed countries at least, there was some evidence that day surgery for this type of cataract extraction may not only be cheaper but just as effective as hospitalisation and overnight stay for cataract extraction. Although the evidence on complications after surgery such as swelling of the cornea, leaking of the wound and temporary increased pressure within the eye was inconclusive, there appeared to be little differences in visual acuity and improvements in quality of life. One of the two studies showed limitations in study design and the way it was run, probably as it was an old study and reported in a less robust way. It provided fewer data for the review. The people included in the studies were representative for the group we were interested in.
The evidence is current to March 2016. In this update, seven randomised controlled trials were identified. Three trials are either not yet recruiting or still recruiting participants and and have not been completed. Four randomised controlled trials with a total of 95 participants were reviewed. These trials were conducted between 1983 and 1995. Data from one of the trials (eight participants) was excluded from the outcome analysis because the conduct of the study was so flawed. All three trials (86 participants) included in the outcome analysis were of adults with acute leukaemia receiving chemotherapy. None of the studies included children. One of these three studies reported funding sources and this study was funded by a charity. In people with haematological disorders who have a low platelet count and would usually be treated with platelet transfusions, we are uncertain whether antifibrinolytics decrease the risk of bleeding and the use of platelet transfusions. We are uncertain whether antifibrinolytics increase the risk of developing a clot. We are uncertain whether antifibrinolytics increases the risk of adverse events. None of the studies reported several of this review's outcomes including overall mortality, adverse events of transfusion, and quality of life. The quality of the evidence was very low, making it difficult to draw conclusions or make recommendations regarding the usefulness and safety of antifibrinolytics. The only evidence available is for adults with acute leukaemia receiving chemotherapy. We await the results of the three ongoing trials that are expected to recruit 1276 participants in total by 2020.
We included 22 randomised controlled studies with 2858 women and performed 13 comparisons, many of which were based on few studies involving small numbers of women. The overall quality of evidence was low. Most trials were conducted in high-income countries. Ten studies, including 1553 women, compared intravenous iron with oral iron. Only one study showed a temporary positive effect on fatigue for intravenous iron. Other anaemia symptoms were not reported. One woman died from heart complications in the intravenous group. Only two studies reported on maternal deaths. Allergic reactions occurred in three women, and heart complications in two women in the intravenous group. Gastrointestinal symptoms were frequent in the oral group and caused some participants to abandon treatment. One study compared red blood cell transfusion with no transfusion. Some (but not all) fatigue scores temporarily improved in the transfused women. Maternal mortality was not reported. When comparing oral iron to placebo (three studies), anaemia symptoms were not reported. It remains unknown whether benefits of oral iron outweigh documented gastrointestinal harms. Other treatment options were compared in other studies, which did not investigate fatigue. Very few studies reported on relief of anaemia symptoms, although this is perhaps the most important purpose of treatment. The body of evidence did not allow us to fully evaluate the efficacy of the treatments on iron deficiency anaemia after childbirth and further research is needed.
We collected all the published studies up to February 2014; there were 41 studies (with 6858 participants) that compared multidisciplinary treatment to other treatments. Most studies compared a multidisciplinary treatment to usual care (such as care by a general practitioner) or to treatments that only addressed physical factors (such as exercise or physiotherapy). All the people in the studies had LBP for more than three months and most had received some other sort of treatment previously. There was moderate quality evidence that multidisciplinary treatment results in larger improvements in pain and daily function than usual care or treatments aimed only at physical factors. The difference was not very large, about 1 point on a 10 point scale for pain, but this may be important for people whose symptoms have not responded to other treatments. There was also moderate evidence that multidisciplinary treatment doubled the likelihood that people were able to work in the next 6 to 12 months compared to treatments aimed at physical factors. While these programs seem to be more effective than alternatives, the effects needs to be balanced with their costs in terms of money, resources and time. Multidisciplinary treatment programs are often quite intensive and expensive, so they are probably most appropriate for people with quite severe or complex problems.
We included in this review 19 trials involving 516 participants. Comparisons included supine position versus prone and different lateral positions (right, left, alternant or quarter for prone). The outcome most often reported in these studies was change in oxygenation. We found no clear evidence that particular body positions in newborn babies who need assisted ventilation are effective in producing relevant and sustained improvement. However, putting infants who receive assisted ventilation in the face-down (prone) position for a short time slightly improves levels of oxygen in the blood (evidence of moderate quality), and these infants undergo fewer episodes of poor oxygenation (evidence of low quality). Researchers described no adverse effects for any of the positions compared, although studies did not last long enough for investigators to detect all possible effects. What's more, most of the babies participating in the studies were placed in alternate positions. For this reason, medium- or long-term adverse effects cannot be attributed to a given position. Confidence in review conclusions depends on the characteristics of included studies such as risk of bias (design limitations), consistency (heterogeneity across studies), precision (small confidence interval) and directness (same effect), and requires that all included studies were published independently of their outcomes. The quality of evidence for these outcomes allows us to have very low to moderate confidence in our conclusions.
We identified 20 relevant randomised controlled trials, with a total of 3791 participants. Eighteen of the 20 studies were funded by pharmaceutical companies. All trials compared systemic antibiotics with other systemic antibiotics. It is unclear whether any particular antibiotic is better than any another for curing infection or avoiding amputation. One trial suggested that ertapenem (an antibiotic) with or without vancomycin (another antibiotic) is more effective than tigecycline (another antibiotic) for resolving DFI. It is also generally unclear whether different antibiotics are associated with more or fewer adverse effects. The following differences were identified: 1. carbapenems (a class of antibiotic) combined with anti-pseudomonal agents (antibiotics that kill Pseudomonas bacteria) produced fewer adverse effects than anti-pseudomonal penicillins (another class of antibiotic); 2. daptomycin (an antibiotic) caused fewer adverse effects than vancomycin or other semi-synthetic penicillins (a class of antibiotic); 3. linezolid (an antibiotic) caused more harm than ampicillin-sulbactam (a combination of antibiotics); 4. tigecycline produced more adverse effects than the combination of ertapenem with or without vancomycin. There were important differences between the trials in terms of the diversity of antibiotics assessed, the duration of treatments, and the point at which the results were measured. The included studies had limitations in the way they were designed or performed, as a result of these differences and design limitations, our confidence in the findings of this review is low.
Until 3 November 2014, we ran computer searches for studies of programs to improve family planning among postpartum women. We wrote to researchers for missing data. Programs had to have contact within six weeks postpartum. The special program was compared with a different program, usual care, or no service. Our main outcomes were birth control use and pregnancy. We found six studies with a total of 5143 women. Of three studies with pregnancy data, two showed fewer pregnancies in the treatment group compared to the control group. The programs in those studies were clinic counseling and community education. All studies showed the special program was related to more birth control use. In two studies, more women in the treatment group used a modern method of birth control than those in the control group. In another study, women in the treatment group were more likely to use pills or an IUD but less likely to use an injectable method. One study used a score for how well the birth control method usually worked. The methods of the treatment group scored higher than those of the control group. A study focused on IUDs showed more IUDs in the treatment group and less use of no method. Women in a health service program used birth control more often than those in a community education program or those getting standard care. Also, women in the health service group were more likely to use the lactation method. We believe the data were very low quality for pregnancy and birth control use. The studies had problems in design, analysis, and reporting. Some did not adjust for factors that could affect the results. They had self-reported outcomes and used different measures for the outcomes. All studies had good follow-up times but most lost many women to follow up.
We include five studies with a total of 715 participants. Three studies were from Italy and two were from the USA. Key results  We looked primarily at the proportion of participants gaining or losing significant vision. The trial comparing grid laser to no laser showed a clear benefit for grid laser. The result of the trial comparing early grid laser to delayed grid laser for macular BRVO (a subgroup of BRVO in which the occlusion is limited to a small vessel draining a sector of the macular region) was uncertain, and the quality of the evidence was low. We could not be certain that bevacizumab injections were better than grid laser treatment, because the effect was imprecise and the quality of the evidence was low. We could not be certain if subthreshold diode laser treatment was better than threshold laser treatment because the results were imprecise. The trial comparing grid laser treatment to triamcinolone (steroid) injection was imprecise, but there was a suggestion of a benefit for grid laser over 1 mg triamcinolone at 36 months and a benefit for grid laser over 4 mg triamcinolone at 24 months. Two of the five studies were at risk of bias, meaning that there were problems with the design and execution of two of the five studies which raised questions about the validity of these two studies. Four of the five studies reported on adverse outcomes. Grid laser was well tolerated within these studies. One participant had an apparent perforation of Bruch's membrane (a membrane under the macula) following laser but this did not affect their vision. Bevacizumab injection was also well tolerated with only minor local side effects (transient red eye and superficial bleeding). Participants receiving triamcinolone injection were at risk of developing a raised eye pressure that required medication or surgery, at risk of developing a cataract, and at risk of developing a serious eye infection (endophthalmitis). Quality of the evidence  Good-quality evidence was available from one trial to support macular grid laser treatment for macular swelling following a blocked vein. There is insufficient evidence to recommend early grid laser, subthreshold laser, bevacizumab injections or triamcinolone injections over grid laser. Anti-VEGF and steroid treatments are becoming increasingly popular for treating eye conditions. However, more studies are needed to assess the longer-term outcome of these treatments against grid laser treatment in the management of macular oedema after branch retinal vein occlusions.
This review found six studies, involving 1902 participants, comparing the long-term efficacy and side effects of tiotropium combined with combination inhalers for treatment of patients with COPD. Not all of the people included in these studies had COPD that was severe enough to be recommended for combined therapy according to current guidelines. Current evidence shows potential benefits of treatment with tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy through increased health-related quality of life and a small improvement i n lung function in patients receiving this combined therapy. However, this evidence does not allow us to draw conclusions about the effects of these treatments on mortality, hospitalisation for all causes and exacerbations. The frequency of serious and non-serious adverse events was not increased in either of the two groups. Overall, we assessed the evidence presented in this review to be of moderate or low quality, which means we are reasonably confident in some of the findings, but less confident in others.
In total, 2431 participants were enrolled in 29 trials. The study sample sizes ranged from 20 to 323 participants, and most of them were middle-aged people recruited from primary or tertiary care. The duration of the treatment programmes ranged from 20 days to 12 weeks, and the number of treatment sessions ranged from one to five sessions per week. Sixteen trials compared MCE with other types of exercises, seven trials compared MCE with minimal intervention, five trials compared MCE with manual therapy, three trials compared MCE with a combination of exercise and electrophysical agents, and one trial compared MCE with telerehabilitation based on home exercises. MCE probably provides better improvements in pain, function and global impression of recovery than minimal intervention at all follow-up periods. MCE may provide slightly better improvements than exercise and electrophysical agents for pain, disability, global impression of recovery and the physical component of quality of life in the short and intermediate term. There is probably little or no difference between MCE and manual therapy for all outcomes and follow-up periods. Little or no difference is observed between MCE and other forms of exercise. Given the minimal evidence that MCE is superior to other forms of exercise, the choice of exercise for chronic LBP should probably depend on patient or therapist preferences, therapist training, costs and safety.
Cinnamon bark has been shown in a number of animal studies to improve blood sugar levels, though its effect in humans is not too clear. Hence, the review authors set out to determine the effect of oral cinnamon extract on blood sugar and other outcomes. The authors identified 10 randomised controlled trials, which involved 577 participants with diabetes mellitus. Cinnamon was administered in tablet or capsule form, at a mean dose of 2 g daily, for four to 16 weeks. Generally, studies were not well conducted and lacked in quality. The review authors found cinnamon to be no more effective than placebo, another active medication or no treatment in reducing glucose levels and glycosylated haemoglobin A1c (HbA1c), a long-term measurement of glucose control. None of the trials looked at health-related quality of life, morbidity, death from any cause or costs. Adverse reactions to cinnamon treatment were generally mild and infrequent. Further trials investigating long-term benefits and risks of the use of cinnamon for diabetes mellitus are required. Rigorous study design, quality reporting of study methods, and consideration of important outcomes such as health-related quality of life and diabetes complications, are key areas in need of attention.
We looked at evidence from randomised, parallel-group studies. Following a comprehensive literature search and assessment of existing trials, we have included 30 studies with a total of 2047 participants. A vast majority of the participants suffered from excessive daytime sleepiness and severe OSA. Duration of studies ranged from four weeks to 12 months. The evidence is current to January 2013. In combining the results from all trials, we found that all three types of interventions increased CPAP usage to varying degrees. Ongoing supportive interventions were more successful than usual care in increasing CPAP usage by about 50 minutes per night. Educational interventions resulted in a modest improvement of about 35 minutes per night. Behavioural therapy increased machine usage by just under one and a half hours per night. Some inconsistency was noted between the results of individual studies, and this introduces some uncertainty about the size of the difference that might be anticipated in practice. It is unclear whether any of these interventions also led to meaningful improvement of daytime symptoms or quality of life. Studies generally recruited people who are new to CPAP, and currently little evidence is available on people who have struggled to persist with treatment. The cost-effectiveness of the interventions has not been explored, and it is unclear which intervention is best suited for individual patients. Overall, the quality of evidence presented is low because of issues with study design and some inconsistency in results across studies. The quality of evidence for symptoms and quality of life was affected by the low number of studies that measured these outcomes.
In this updated review, we included a total of 12 studies (including five new studies), involving 1954 participants. Six Chinese herbal medicines may facilitate the improvement of symptoms and increase the rate of recovery. Two studies separately reported one case of diarrhoea and one case of mild nausea; two trials reported no adverse events in the treatment group; and other studies did not report any adverse events. We identified ten studies as being of poor methodological quality and only two studies as being of medium methodological quality. Chinese medicinal herbs may be the treatment choice for sore throat, but we cannot recommend any particular preparation or formulation over another as we did not find any well-designed studies to provide strong evidence to conclusively support or reject the use of Chinese traditional herbal medicines in the treatment of sore throat. Enhancing the quality of research into Chinese medicinal herbs for sore throat is imperative, and stronger evidence from high quality, randomised controlled trials (RCTs) are needed.
We searched for clinical trials up to 11 January 2017, and we included three studies with 330 people who had been diagnosed with small-cell lung cancer which had not spread outside the chest. Some were given surgery only, and some were not. Also, some were given chemotherapy and radiotherapy along with their surgery, and some were given chemotherapy and radiotherapy without surgery. We looked for a difference in how long people lived, and if their treatment caused any side effects. Key findings The data were all of very low quality. All three studies were quite different so could not be combined. One study reported that people lived longer without surgery (but with radiotherapy) than with surgery. One study reported 4% of people surviving at two years with surgery compared to 10% of people surviving with radiotherapy. One study reported 52% of people surviving with surgery compared to 18% of people surviving with radiotherapy. Our evidence does not support the use of surgery for people with small-cell lung cancer, but the quality of data is low and from more than 20 years ago. Better trials are needed to properly compare surgery with no surgery in people with small-cell lung cancer. Quality of the evidence We rated the quality of the evidence using one of the following grades: very low, low, moderate, or high. Very low quality evidence means we are uncertain about the results. High-quality evidence means we are very certain about the results. For this Cochrane Review, we found that the evidence was of very low quality for all the outcomes studies. We could not combine the trials as they were all very different, and the trials were very old. Some trials did not give enough information about their quality.
This systematic review evaluates the effectiveness of azapirones compared to other treatments. From the results of 36 randomized controlled trials, azapirones appear to be superior to placebo in short-term studies (four to nine weeks) but may not be superior to benzodiazepines. We were unable to conclude if azapirones were superior to antidepressants, psychotherapy or kava kava. As GAD is generally chronic in nature, conclusions about azapirones' long-term efficacy are not able to be made and longer term trials are needed.
24 studies involving 4418 women. The evidence is current to May 2015. Five of the 24 studies specifically assessed women with mTNBC while the other 19 studies assessed women with metastatic breast cancer in general (mainly women without mTNBC). This review found that, compared to chemotherapy without platinum, chemotherapy with platinum did not increase survival time by any important degree for women with metastatic breast cancer in general (mainly women without mTNBC). The quality of the evidence for this was considered to be high, meaning that we are confident about the results. For women with mTNBC, however, this review found that chemotherapy containing platinum may increase survival time over chemotherapy without platinum, but the quality of the evidence for this is low at this point in time (largely due to the small number of studies that have assessed mTNBC). This review also found that chemotherapy including platinum reduced the number of breast cancer recurrences compared to chemotherapy that did not contain platinum in women with mTNBC, however these findings also currently come from low-quality evidence. There was no difference in the number of breast cancer recurrences for women receiving platinum or non-platinum chemotherapy for metastatic breast cancer in general. Chemotherapy with platinum was more likely to shrink tumours compared to chemotherapy without platinum, but this result needs to be considered cautiously. Compared with women receiving chemotherapy without platinum, women receiving chemotherapy with platinum experienced higher rates of nausea/vomiting, anaemia, leukopenia and hair loss. it is difficult to justify using chemotherapy containing platinum for the treatment of metastatic breast cancer that is not mTNBC, given that similarly effective but less toxic chemotherapy is commonly available. Chemotherapy containing platinum may provide a survival benefit to mTNBC participants of sufficient magnitude to justify its use, but the quality of the evidence for this is low at this point in time. Further studies are required before a more definitive conclusion can be made.
Twelve studies with a total of 12,168 patients were included in this review. The analyses show that, in patients with IC, antiplatelet agents reduced the risk of death from all causes, and from heart attack and stroke combined when compared with placebo. When aspirin was compared with other antiplatelet agents, there was some evidence that the alternative antiplatelet had a more beneficial effect in reducing all cause mortality or of suffering a cardiovascular event such as heart attack or stroke. However, this was based on only two trials. Antiplatelet usage, however, does increase the risk of indigestion and may also increase risk of major bleeding events. Despite its widespread use, the evidence for first line use of aspirin in patients with IC is weak and further research is required to determine whether aspirin would be better replaced by a different class of antiplatelet agent which has a greater beneficial effect with fewer side-effects.
We searched for studies evaluating the effect of early administration of antiepileptic drugs or other potentially neuroprotective agents (which act by protecting the structure or function of nerves) on post-traumatic epilepsy. The primary outcomes of interest were early post-traumatic seizures (within one week of trauma) and late seizures (later than one week post-trauma). We also looked at death, time to late seizure and side effects. The evidence is current to January 2015. We found 10 clinical trials involving 2326 people reported in 12 published articles. The evidence available indicated that early treatment with a traditional antiepileptic drug (phenytoin or carbamazepine) may reduce the risk of early post-traumatic seizures. Traditional antiepileptic drugs are no more effective than placebo (a pretend pill) or standard care in reducing late seizures or mortality. Limited data were available for the comparison of an AED with another AED and for the comparison of other potentially neuroprotective agents with placebo. Most studies did not report serious side effects and other side effects. The overall quality of the evidence varied and findings should be interpreted with caution.
Four trials enrolled approximately 1700 participants and lasted between nine months and two years. Study participants were aged from one month to 15 years. There were different results on the occurrence of nutritional rickets in different settings. Adverse effects were investigated in one study only.  Considering the partial high frequency of nutritional rickets, the obvious way of action of supplementation of vitamin D or calcium and the favourable risk-benefit ratio, preventive measures are reasonable in high risk groups like infants and toddlers. New studies investigating main and side effects of preventive measures against nutritional rickets in different age groups and in different countries are indicated.
We identified 40 studies enrolling 4137 adult participants. Of these, 35 studies in 4039 adults compared convective dialysis with standard haemodialysis. Overall the evidence in the studies was low or very low quality due to limitations in the methods used in the research leading to low confidence in the results. Overall, there was no evidence convective dialysis lowered risk of death from any cause but may reduce death due to heart or vascular disease. Overall treating 1000 men and women who have end-stage kidney disease with convective dialysis rather than standard haemodialysis may prevent 25 dying from heart disease. Convective therapy may reduce blood pressure falls during dialysis but there was no evidence that convective dialysis influenced chances of hospital admission or other side-effects, or improved quality of life.
In January 2017, we found eight clinical studies that examined 315 people. We included TENS administered to produce a non-painful 'tingling' sensation at the site of pain either as a treatment alone or combined with exercise treatment. All studies used TENS in comparison with 'fake' (called placebo or sham) TENS, no treatment, or other treatments such as medicine or hydrotherapy (treatment in water). We did not find enough high-quality studies to allow us to come to any conclusions about the effectiveness of TENS for fibromyalgia pain. Even though seven studies concluded that TENS relieved pain associated with fibromyalgia, the studies were low quality and the findings for measures of pain were inconsistently reported. Studies did not measure most of our outcomes and it was not always clear what aspects of pain were being reported (e.g. present pain, remembered pain, pain severity, etc.). Only one small pilot study found that one 30-minute treatment of TENS reduced pain on movement during and immediately after treatment; however, there were too few participants observed and it is unknown whether this effect would be maintained over a longer course of TENS treatments. Overall, it is not possible to judge whether TENS reduces pain associated with fibromyalgia. There were no serious side events reported in any of the studies. We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The quality of the evidence was very low overall because of a lack of data.
Evidence is current to May 2014. We included seven studies with 492 participants from five different countries and included 422 participants in our analysis. Most participants were middle-aged. Participants had almost no diseases other than their reason for having surgery. The type of surgery was planned abdominal surgery. Three of the seven studies looked only at obesity surgery. Participants received dexmedetomidine right before or during their abdominal surgery. Six studies compared dexmedetomidine with no treatment, and one small study compared dexmedetomidine with fentanyl (a strong opioid). We reran the search in May 2015 and found nine studies of interest, which we will discuss when we update the review. In total, 13 studies are awaiting classification. Most of the studies that compared dexmedetomidine with no treatment found that dexmedetomidine reduced the need for opioids for treating pain for 24 hours after surgery. During the same period, no important differences in pain were noted, except one study (80 participants) showed a reduction in intensity of pain at two hours after surgery with dexmedetomidine. The quality of the evidence was very low because the results were not similar across studies, and because some studies were poorly conducted. The influence of dexmedetomidine on postoperative nausea and vomiting could not be determined because results were not similar across studies. No conclusion could be made for bowel function and mobilization and side effects such as postoperative sedation, as data were insufficient. One study with 80 participants reported a higher rate of low blood pressure ('low' meaning that medication was required) for participants receiving a high dose of dexmedetomidine compared with no treatment, but for lower doses of dexmedetomidine, they noted no differences compared with no treatment. For the comparison dexmedetomidine versus fentanyl, data were insufficient to allow conclusions (only one small study). Dexmedetomidine - compared with no treatment - seemed to reduce the need for opioids without worsening the experience of postoperative pain after abdominal surgery in adults. However, the quality of evidence was very low because studies were poorly conducted and because results were not similar across studies. The importance of these findings for patients was also uncertain because the influence of dexmedetomidine on bowel function, mobilization and adverse effects could not be properly determined.The seven included studies were small, so side effects associated with use of dexmedetomidine may be greater than this review reported. In addition, we could not obtain relevant data from several studies because investigators mixed abdominal surgery with other types of surgery.
Antibiotics are administered to pregnant women during the second and third trimester of pregnancy (before labour) to prevent bacteria in the vagina and cervix affecting the pregnancy. Infection by some infectious organisms in a woman’s genital tract can cause health problems for the mother and her baby, and has been associated with preterm births. This review of eight randomised trials involved approximately 4300 women in their second or third trimester. We found that antibiotics did not reduce the risk of preterm prelabour rupture of the membranes (one trial, low quality of evidence), or the risk of preterm birth (six trials, highquality of evidence). Preterm delivery was reduced in pregnant women who had a previous preterm birth and an imbalance of bacteria in the vagina (bacterial vaginosis) during the current pregnancy. There was no reduction in preterm delivery in pregnant women with previous preterm birth without a bacterial imbalance during the current pregnancy (two trials). Postpartum endometritis, or infection of the uterus following birth, was reduced overall (three trials, moderate quality of evidence), as well as in a trial of high-risk women who had a previous preterm birth (one trial, moderate quality of evidence). No reduction in neonatal illness was observed. Outcomes of interest were available in trials with high losses to follow-up. We could not estimate the side effects of antibiotics since side effects were rare; however, antibiotics may still have serious side effects on women and their babies. There is, therefore, no justification to give antibiotics to all pregnant women during the second or third trimester to prevent adverse infectious effects on pregnancy outcomes.
We searched the medical literature for trials of vitamin C in CMT disease and found six trials - five in adults and one in children - on the treatment of CMT type 1A (CMT1A) with vitamin C. All compared vitamin C doses of 1 to 4 grams per day with a placebo (a dummy or sugar pill disguised as vitamin C), and lasted for 12 or 24 months. The trials in adults included a total of 622 people. The other trial included 80 children. The main measure of the effects of vitamin C in this review was change in impairment. We also collected information on disability, nerve conduction studies, sensation, muscle strength, quality of life and harmful effects of vitamin C. We found that ascorbic acid treatment did not improve impairment from CMT1A in adults as measured by the CMT neuropathy score (CMTNS). In children, the CMTNS was not reported, as it is a measure developed for adults with CMT. The measures used for children in this study did not show benefit from vitamin C. The studies were largely at low risk of bias, meaning they were well designed and the results were not easily influenced by chance. Adverse events were similar in nature and number in vitamin C and placebo groups. There is high-quality evidence for adults and low-quality evidence for children that vitamin C does not improve the course of CMT1A. However, CMT progresses slowly, so the study durations of 12 or 24 months may not have been long enough to detect effects of treatment. Further research with longer study duration and more sensitive outcome parameters should be done, although any large effect in adults or children is unlikely.
This review aimed to assess the effectiveness and safety of single dose dipyrone in adults with moderate/severe renal colic pain but there were too few data to obtain clear results. The data available indicated that intravenous dipyrone was more effective than intramuscular dipyrone, and combining dipyrone with antispasmolytic agents did not improve its efficacy. Commonly reported side effects included dry mouth and drowsiness, and some patients experienced pain at the injection site. Agranulocytosis was not reported.
We updated the search on 30 June 2016. We identified three studies, with a total of 1915 babies. One study could not be included in the analysis and so findings are based on two studies involving 1302 infants. The mothers in the studies were motivated to breastfeed recruited immediately after birth and at two weeks of life, respectively. We found that unrestricted use of a pacifier did not affect the proportion of infants exclusive or partial breastfeeding at three and four months. The studies were remarkably consistent. We judged this to be moderate-quality evidence. There was no information on the effect of pacifier use on any breastfeeding difficulties experienced by the mothers, maternal satisfaction, infant crying and fussing and infant problems such as otitis media and dental malocclusion. In motivated mothers, there is moderate-quality evidence that pacifier use in healthy term breastfeeding infants before and after lactation is established does not reduce the duration of breastfeeding up to four months of age. However, there is insufficient information on the potential harms of pacifiers on infants and mothers. Until further information becomes available on the effects of pacifiers on the infant, mothers who are well-motivated to breastfeed should be encouraged to make a decision on the use of a pacifier based on personal preference.
We searched databases from their inception to August 2018 and found five studies that met the inclusion criteria. Three studies compared extended-field RT versus pelvic RT. None of these three studies compared against the current gold-standard of pelvic CRT. One study compared extended-field RT versus pelvic CRT and one study compared extended-field CRT versus pelvic CRT. Compared with pelvic RT alone, women given extended-field RT may have been less likely to die and probably were less likely to have a cervical cancer come back (recurrence) in the para-aortic lymph nodes. However, extended-field RT may have made little or no difference to how often their cancer recurred elsewhere and how often they experience severe side effects. Pelvic CRT is the modern standard of treatment for locally advanced cervical cancer. In a comparison of extended-field RT alone versus pelvic CRT, women given pelvic CRT were probably less likely to die or have recurrence of their cancer. Women given extended-field RT alone may have been less likely to experience a recurrence within the para-aortic lymph nodes and have had adverse events during or shortly after treatment. There were no clear differences regarding the late adverse events between the two groups. Women given extended-field CRT may or may not have been less likely to die or have cancer progression than those women pelvic CRT. There were no clear differences in the chances of experiencing a cancer recurrence in the para-aortic lymph nodes and severe side effects between the groups. The evidence for outcomes in the comparison of extended-field RT alone versus pelvic RT alone were of moderate certainty. In the comparison of extended-field RT versus pelvic CRT, the evidence regarding the survival and side effects were of moderate certainty. The evidence for para-aortic recurrence was of low certainty. The evidence for all outcomes in a comparison of extended-field CRT versus pelvic CRT were of very-low certainty because of concerns regarding the high risk of bias and results coming from a single trial of very few women. We are moderately certain that, compared with pelvic RT alone, extended-field RT probably improves overall survival and reduces risk of para-aortic lymph node recurrence. However, pelvic RT alone would now not be considered the standard of care in women well enough to receive CRT, so these results should be reviewed with caution and cannot be extrapolated to modern treatment techniques. Low- to moderate-certainty evidence supports the use of pelvic CRT rather than extended-field RT alone, as it appears to reduce the risk of death and cancer progression. The likelihood of experiencing unwanted side effects during treatment was higher among women receiving pelvic CRT than extended-field RT. Evidence comparing extended-field CRT to pelvic CRT was very low certainty regarding outcomes and it may or may not improve survival.
Eleven trials were included in this review, ten comparing vitamin A with a control (placebo or no supplementation) and one comparing different vitamin A regimens. The search for eligible trials was updated in May 2016. Compared to the control group, supplementing very low birth weight infants with vitamin A appears to have a small benefit in reducing the risk of death or oxygen requirement at one month of age and the risk of chronic lung disease (oxygen requirement) at 36 weeks' postmenstrual age (moderate-quality evidence). There was a marginal reduction of the combined outcome of death or chronic lung disease (moderate-quality evidence). Although there is a statistical reduction in chronic lung disease, these findings are consistent with either a meaningful impact on chronic lung disease or a negligible impact. The one trial that investigated neurodevelopmental status at 18 to 22 months of age correcting for prematurity found no evidence of benefit or harm associated with vitamin A supplementation compared to control (low-quality evidence). No adverse effects of vitamin A supplementation were reported, but it was noted that intramuscular injections of vitamin A were painful. Whether clinicians decide to utilise repeat intramuscular doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of this outcome and the value attached to achieving a modest reduction in the outcome balanced against the lack of other proven benefits and the acceptability of the treatment. Information on long-term neurodevelopmental status suggests no evidence of either benefit or harm from the intervention.
We reviewed all known studies that evaluated home palliative care services, i.e. experienced home care teams of health professionals specialised in the control of a wide range of problems associated with advanced illness – physical, psychological, social, spiritual. We wanted to see how much of a difference these services make to people's chances of dying at home, but also to other important aspects for patients towards the end of life, such as symptoms (e.g. pain) and family distress. We also compared the impact on the costs with care. On the basis of 23 studies including 37,561 patients and 4042 family caregivers, we found that when someone with an advanced illness gets home palliative care, their chances of dying at home more than double. Home palliative care services also help reduce the symptom burden people may experience as a result of advanced illness, without increasing grief for family caregivers after the patient dies. In these circumstances, patients who wish to die at home should be offered home palliative care. There is still scope to improve home palliative care services and increase the benefits for patients and families without raising costs.
We found only two studies enrolling 64 infants. In one of the two studies, there was a low risk of bias whereas in the second study there were concerns about how the infants had been put into treatment groups, and whether parents and doctors were aware of which treatment was given (random sequence generation, allocation concealment and blinding of outcomes assessment). We found no studies that received funding from the industry. Prophylaxis with cromolyn sodium did not result in an important effect on the combined outcome of mortality or chronic lung disease at 28 days of age, chronic lung disease at 28 days; chronic lung disease at 28 days or at 36 weeks' PMA; or chronic lung disease in survivors at 28 days or at 36 weeks' PMA. This review of trials found no strong evidence that cromolyn sodium can prevent or reduce chronic lung disease and further research does not seem to be justified. The quality of evidence was low for most measures.
Our first comparison was based on 18 trials and 2074 women. The women who were given chemotherapy either more than a fortnight apart or with a less intense dose of cisplatin before their radiotherapy, did not live as long as those who were only given radiotherapy. However, women given chemotherapy either less than a fortnight apart or with a more intense dose of cisplatin before their radiotherapy, seemed to live longer than those who were only given radiotherapy. These second results are based on less data and are not so convincing. There were very few serious side effects that continued long after treatment and they seemed to be similar whether chemotherapy was given or not. Our second comparison was based on 5 trials and 872 women. The women who were given chemotherapy before surgery seemed to live longer than those who were only given radiotherapy. However, there was a small amount of data, there were differences between results of trials and other treatments were used. Therefore, it is not clear if the benefit might be for reasons other than the chemotherapy. Further assessment of neoadjuvant chemotherapy in randomised trials is required. It may be valuable to compare it to a combined chemotherapy and radiotherapy approach or even to use neoadjuvant chemotherapy together with combined chemotherapy and radiotherapy.
DOAC probably reduced the incidence of stroke and systemic embolic events as a primary efficacy outcome, compared to warfarin. Further, DOAC might slightly reduce the incidence of major bleeding events as a primary safety outcome, compared to warfarin. This review demonstrated that DOAC are as likely as warfarin to prevent all strokes and systemic embolic events without increasing major bleeding events among AF patients with CKD. According to GRADE, the quality of the evidence was moderate for the primary efficacy outcome because of concerns with imprecision and low for the primary safety outcome because of concerns with inconsistency and imprecision. The results of this study chiefly apply to CKD stage G3 patients, since we could not assess those with CKD stage G4 or G5.
A total of seven studies with 1410 preterm infants were included in this review. Most of these initial studies were conducted between 1980 and 1990. Preterm infants treated with ethamsylate had similar outcomes with respect to death and disability at the age of two years when compared to infants who were treated with a placebo. Infants born less than 35 weeks gestation appeared to have less intraventricular haemorrhage when treated with ethamsylate compared to controls, however this did not lead to improved developmental outcome in later childhood. There were no adverse effects noted with ethamsylate treatment. Based on these results, routine use of ethamsylate for prematurely born infants to prevent intraventricular haemorrhage cannot be recommended. It is highly unlikely that any further trials will be conducted to explore this clinical question.
This review examined 22 randomised clinical trials where 2902 women took part in the studies; 1499 in the CHM group and 1403 in the control group which might include a placebo (non-active compound made to look, taste and smell the same as the study compound) or a drug or HT or another CHM formula (different from the one being tested). Most of the studies had a trial period for 12 weeks. The data are current to March 2015. We found insufficient evidence that CHM were any more or less effective than placebo or HT for the relief of vasomotor symptoms. Adverse effects were not well reported, some women taking CHM reported mild diarrhoea, breast tenderness, gastric discomfort and an unpleasant taste. Effects on safety were inconclusive. The quality of the evidence ranged from very low to moderate. The studies did not produce good quality evidence to allow the authors to draw a conclusive statement regarding the effectiveness or safety of CHM.
We searched for studies comparing additional steroid treatment with no additional steroid treatment in individuals with influenza. The evidence is current to 3 October 2018. We identified a total of 30 studies with 99,224 individuals; one of these studies was a clinical trial. The majority of studies investigated adults admitted to hospital with pandemic influenza in 2009 and 2010. We found one relevant clinical trial, but there were very few participants (n = 24) with laboratory-confirmed influenza. The certainty of the evidence available from existing observational studies was of very low. We found that people with influenza who received additional steroid treatment may have a greater risk of death compared to those who did not receive steroid treatment. Hospital-acquired infection was the main 'side effect' related to steroid treatment reported in the included studies; most studies reported a greater risk of hospital-acquired infection in the group treated with steroids. However, it was unclear whether patients with more severe influenza had been selected to receive steroid treatment. Consequently, we were unable to determine whether additional steroid treatment in people with influenza is truly harmful or not. Further clinical trials of additional steroids in the treatment of individuals with influenza are therefore warranted. In the meantime, the use of steroids in influenza remains a clinical judgement call. In the one controlled trial there were only 24 participants with confirmed influenza infection, and there was under-representation of the sickest patients in the intensive care unit and with sepsis. The rest of the evidence was from observational studies, and we classified the certainty of this evidence as very low. A major limitation was that the indications for corticosteroid therapy were not fully specified in many of the studies; corticosteroids may have been used as a final attempt in people with the most severe disease, or conversely they may have been used to treat less severe illnesses that occurred simultaneously such as asthma exacerbations. It was noted in some studies that there was high degree of association between the use of corticosteroids and the presence of potentially confounding factors such as disease severity and underlying illnesses, suggesting that confounding by the indication for corticosteroids was likely if not adjusted for when determining effect estimates. We noted inconsistent reporting of other important variables that may be related to influenza-related death across studies, including time to hospitalisation, the use and timing of antiviral drugs and antibiotics, and the type, dose, timing, and duration of corticosteroid therapy. Additionally, for studies in which this information was reported, there were differences between studies in the way that disease severity was measured, the time point at which death was assessed, and the proportions of cases and controls treated with antivirals and/or antibiotics and in the type, dose, timing, and duration of corticosteroid therapy.
Short-term studies indicate that people with chronic obstructive pulmonary disease respond to the administration of oxygen when they do exercise tests. Ambulatory oxygen is the use of supplemental oxygen during exercise and activities of daily living. One way to assess if ambulatory oxygen is beneficial for a patient with COPD is to compare the effects of breathing oxygen and breathing air on exercise capacity. Some people with COPD may benefit more than others, and trials should take account of whether people who do not already meet criteria for domiciliary oxygen also respond. This review shows that there is strong evidence that ambulatory oxygen (short-term) improves exercise capacity. Further research needs to focus on which COPD patients benefit from ambulatory oxygen, how much oxygen should be provided and the long-term effect of ambulatory oxygen.
We found two studies, undertaken in the 1990s in high-income countries, but their quality was unclear. One study, involving 307 women, compared routine vaginal and rectal examinations in labour. Here, fewer women reported that vaginal examinations were very uncomfortable compared with rectal examinations. The other study, involving 150 women, compared two-hourly and four-hourly vaginal examinations, but no difference in outcomes was seen. We identified no convincing evidence to support, or reject, the use of routine vaginal examinations in labour, yet this is common practice throughout the world. More research is needed to find out if vaginal examinations are a useful measure of both normal and abnormal labour progress. If vaginal examination is not a good measure of progress, there is an urgent need to identify and evaluate an alternative measure to ensure the best outcome for mothers and babies.
Eight trials (468 participants) are included in this review. Data analysis did not demonstrate any significant effect in the subjective loudness of tinnitus. We found, however, a significant improvement in the depression associated with tinnitus and quality of life (decrease of global tinnitus severity), suggesting that cognitive behavioural therapy has a positive effect on the way in which people cope with tinnitus. Further research should use a limited number of validated questionnaires in a more consistent way and with a longer follow up to assess the long-term effect of cognitive behavioural therapy in patients with tinnitus.
We included four studies with a total of 209 patients, ranging in age from 23 to 85 and with more men than women. All the studies allowed the use of hearing aids for a total period of at least eight weeks before questions were asked about their preference for one or two aids. In all the studies the patients had bilateral hearing loss but there was considerable variation in what type of hearing loss they suffered from and how bad their hearing was. Three of the studies were published before the mid-1990s and the fourth study was published in 2011. Therefore, only the most recent study used 'modern' hearing aids similar to those that are widely available in high-income countries. Of the four studies, two were conducted in the UK in National Health Service (NHS – public sector) patients. One of these looked at patients from primary care whose hearing loss had been picked up by a screening programme. The other looked at patients whose primary care practitioner thought they might benefit from hearing aids so had referred them to the local ENT department to get them. The other two studies were conducted in the United States: one study recruited only people on active military duty, or who had served in the military and had hearing loss due to being exposed to loud noises. About half of the people in the other study were ex-military. Only one of the outcomes we thought was most important - patient preference - was reported in all studies. The percentage of patients who preferred two hearing aids to one varied between studies: this was 54% (51 out of 94), 39% (22 out of 56), 55% (16 out of 29) and 77% (23 out of 30), respectively. We did not combine the numbers from these four studies because it would not have been right to do so. We graded the quality of evidence for this outcome as very low on a scale that goes high – medium – low – very low. There was no information in the four studies on the other outcomes we were interested in. This review identified only four studies comparing the use of one hearing aid with two. The studies were small and included people of widely varying ages. There was also considerable variation in the types of their deafness and in how deaf they were. For the most part, the types of hearing aid evaluated would now be regarded, in high-income countries, as 'old technology', with only one study looking at 'modern' digital aids. However, we do not know if this is relevant or not. This review did not look at the differences between other 'old' and 'new' types of hearing aid. We could not combine the numbers from the four studies. Overall, this fact and the very low quality of the evidence leads us to conclude that we do not know if patients have a preference for one aid or two. Similarly, we do not know if a patient's quality of life is better with one or two aids.
We found 17 randomised controlled trials (with 556 participants) to include in this review. We rated the quality of evidence provided by most of the included studies to be between low and very low. The studies could be divided into three different types of interventions: (1) exposure to bright light; (2) a napping opportunity during the night shift; or (3) others, like physical activity or sleep education. Bright light Almost all of the bright light studies we looked at had some problem with the way they were designed. This problem made it difficult to know if any differences in sleepiness and sleep between those receiving bright light and those not receiving bright light were truly because of the bright light intervention. The studies were also too different in the types of bright light they used and types of light that the control groups received to compare them to one another. Napping The studies in the napping group did not report enough information for us to be certain whether napping helps shift workers feel more awake. The studies were very short, with each study lasting only a single night. Others This group of studies, which included, for example, physical exercise and sleep education, also reported too little information for us to say whether these interventions can make shift workers less sleepy on-shift or help them sleep longer and better after their shift. We conclude that there is too much uncertainty to determine whether any person-directed, non-drug interventions can really affect shift workers with sleepiness and sleep problems. We need studies that are better designed, report their designs and results more clearly, include more participants and last for a longer time before we can be certain. Studies also need to find out if their participants are 'morning-types' or 'evening-types', to be sure that the right type of shift worker gets the right type of intervention. We searched for studies that had been published up to August 2015.
Vitamin C has been proposed for treating respiratory infections since it was isolated in the 1930s. It became particularly popular in the 1970s when Nobel laureate Linus Pauling concluded from earlier placebo-controlled trials that vitamin C would prevent and alleviate the common cold. Over two dozen new trials were undertaken thereafter. Vitamin C has been widely sold and used as a preventive and therapeutic agent. This review is restricted to placebo-controlled trials testing 0.2 g/day or more of vitamin C. Regular ingestion of vitamin C had no effect on common cold incidence in the ordinary population, based on 29 trial comparisons involving 11,306 participants. However, regular supplementation had a modest but consistent effect in reducing the duration of common cold symptoms, which is based on 31 study comparisons with 9745 common cold episodes. In five trials with 598 participants exposed to short periods of extreme physical stress (including marathon runners and skiers) vitamin C halved the common cold risk. The published trials have not reported adverse effects of vitamin C. Trials of high doses of vitamin C administered therapeutically, starting after the onset of symptoms, showed no consistent effect on the duration or severity of common cold symptoms. However, only a few therapeutic trials have been carried out and none have examined children, although the effect of prophylactic vitamin C has been greater in children. One large trial with adults reported benefit from an 8 g therapeutic dose at the onset of symptoms, and two therapeutic trials using five-day supplementation reported benefit. More trials are necessary to settle the possible role of therapeutic vitamin C, meaning administration immediately after the onset of symptoms.
All these trials had high risk of bias (that is risk of overestimation of benefits and underestimation of harms). We compared any kind of T-cell antibody induction versus no induction. Furthermore, we compared interleukin-2 receptor antagonists versus no induction, monoclonal T-cell antibody versus no induction, interleukin-2 receptor antagonists versus monoclonal antibody (other than IL-2 RA) induction, interleukin-2 receptor antagonists versus polyclonal antibody induction, and monoclonal antibody (other than IL-2 RA) induction versus polyclonal antibody induction. We found no significant differences in incidence of survival, and we found no significant difference in adverse effects (e.g. infection, cytomegalovirus infection, post-transplantation lymphoproliferative disorder, cancer, chronic allograft vasculopathy, renal function, hypertension, diabetes mellitus, or hypertension) for any of the comparisons. The incidence of acute rejection may occur less frequently in patients treated with interleukin-2 receptor antagonist induction compared with no induction , and in patients treated with polyclonal antibody induction compared with interleukin-2 receptor antagonist induction. However, systematic errors and random errors cannot be excluded, and our findings were dependent upon choice of statistical model. Accordingly, our observations are not robust and more trials are needed to confirm or reject these findings.
Authors from Cochrane Oral Health carried out this review of existing studies and the evidence is current up to 12 June 2018. We included 71 trials that involved 3780 adults who underwent tooth whitening procedures with various bleaching agents using different methods of application, length of application and duration of treatment. 26 studies compared a bleaching agent to placebo and 51 studies compared one bleaching agent to another bleaching agent. The bleaching agents whitened teeth compared to placebo over a short time period (from 2 weeks to 6 months), however the certainty of the evidence is low to very low. The evidence currently available is insufficient to draw reliable conclusions regarding the superiority of home-based bleaching compositions or any particular method of application or concentration or application time or duration of use. The most common adverse events were tooth sensitivity and oral irritation, which were reported with higher concentrations of active agents, although the effects were mild and transient. Well-planned randomised controlled trials need to be conducted by standardising methods of application, concentrations, application times and duration of treatment. The overall certainty of the evidence was low to very low for all comparisons. This was because most of the comparisons were reported in single trials with small sample sizes and event rates. There was an unclear risk of bias in most of the trials.
The evidence is current to September 2016. Four studies included individuals with a prior heart attack or stroke or with a high predicted risk for having an initial heart attack and five studies had long-term (12 months or more) follow-up. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Most study participants were middle-aged men with moderate elevations in blood pressure or cholesterol. Two studies specifically included ethnic Aboriginal or Maori minorities in half of the study participants. The fixed-dose combinations ranged from two to five drugs; all studies included at least one blood pressure-lowering and one cholesterol-lowering drug. The effects of fixed-dose combination drug therapy on all-cause mortality and fatal and non-fatal heart attacks and strokes are uncertain, primarily due to the low number of participants experiencing these events in these studies (fewer than 5% for both) and comparisons with usual care (low-quality evidence). Fixed-dose combination drug therapy leads to more adverse events than control (32% versus 27%), including placebo (moderate-quality evidence). This information is not surprising since aspirin, blood pressure-lowering drugs and cholesterol drugs are known to increase the risk for side effects compared with placebo. Fixed-dose combination therapy may modestly lower blood pressure (˜6 mmHg) and cholesterol (-0.6 mmol/L in LDL cholesterol), but these effects were not consistent (moderate-quality evidence for blood pressure and LDL cholesterol but low-quality evidence of total cholesterol). Fixed-dose combination therapy appears to improve adherence to medications to prevent ASCVD (moderate-quality evidence). The quality of evidence from these studies generally ranged from moderate to low. Ongoing trials of fixed-dose combination drug therapy will likely inform clinical endpoints to guide decision-making.
We found three trials comparing groups of adults treated with bronchial thermoplasty versus adults who received standard medical treatment or a "sham" (simulated) bronchial thermoplasty treatment. These studies showed moderate improvement only in quality of life of patients treated with bronchial thermoplasty and in the number of asthma attacks (exacerbations) that they experienced. In addition, patients treated with this procedure had more respiratory problems than patients who received the alternative intervention during the period when they were undergoing treatment, resulting in increased risk of hospitalisation due to a respiratory symptom during this phase, but not afterward. Confidence in the results of this review is moderate because two of the studies had no sham intervention and there were differences regarding the characteristics of patients and the comparisons performed. More studies should be conducted to determine whether the observed effect and safety of bronchial thermoplasty are durable over the long term, and to identify whether particular patients can be identified who could benefit most. This plain language summary is current as of January 2014.
We included 10 studies of iron. These 10 studies included 428 people with restless legs syndrome. Not all participants had low blood levels of iron. All participants were adults. Most of the studies used injections of iron, while three studies used iron in pill form. Iron treatment was compared to a non-active treatment (i.e. a placebo) in nine studies. In one study, iron was compared to another restless legs syndrome treatment called a dopamine agonist. The main measure of interest in our review was the severity of restlessness. This was usually measured using a 10-question survey regarding severity and effects of urges to move the legs, called the International Restless Legs Syndrome Severity Rating Scale (IRLS). This was measured 2-4 weeks after injections of iron and 12-14 weeks after iron in pill form. Four trials were funded by the drug manufacturer. Two trials were funded by the USA National Institutes of Health. Two trials were funded by the workplaces of the study investigators. Two studies did not report who funded the study. The four studies funded by drug manufacturers were the largest. The studies funded by drug companies contributed over half of the total number of participants. Overall, the studies showed that iron is better than a placebo for reducing the severity of restless legs syndrome symptoms, although the benefit was low to moderate. This is mostly based on studies using injections of iron, rather than iron pills. Iron was helpful even if blood iron levels were normal at the start of the study. The quality of the evidence was moderate, because not all completed studies have been published, not all important outcomes have been measured, and not enough people have been studied. Side effects were not more common with iron than with placebo. Based on one study, side effects were less common with iron than with another commonly used restless legs syndrome treatment, although the certainty in this result is very low. More studies are needed to allow people with RLS and doctors to make decisions about who should take iron for restless legs syndrome treatment, using what type of iron, and for how long. The evidence is current to September 2017.
We performed a systematic review of medical databases to find clinical trials that compared the effects of acupuncture to controls (sham (pretend) acupuncture, no treatment, or medicines) on blood pressure and safety in adults with hypertension. The results are current to February 2017. We found 22 trials including 1744 people. The trials did not look at death and general health. Four trials compared acupuncture with sham acupuncture and suggested a small short-lasting (one to 24 hours) reduction in blood pressure. The other trials were of very poor quality. There was no evidence for a long-lasting lowering of blood pressure by acupuncture that would be useful in the treatment of hypertension. We could not assess the safety of acupuncture as few trials reported this. At present, there is no evidence that acupuncture is useful in the management of long-lasting hypertension. Future trials must be designed to measure a sustained blood pressure lowering effect of acupuncture.
This review assessed the effects of providing dietary advice to follow a Mediterranean-style diet or provision of foods relevant to the diet (or both) to healthy adults, people at increased risk of cardiovascular disease and those with cardiovascular disease, in order to prevent the occurrence or recurrence of cardiovascular disease and reduce the risk factors associated with it. Definitions of a Mediterranean dietary pattern vary and we included only randomised controlled trials (RCTs) of interventions that reported both of the following key components: a high monounsaturated/saturated fat ratio (use of olive oil as main cooking ingredient and/or consumption of other traditional foods high in monounsaturated fats such as tree nuts) and a high intake of plant-based foods, including fruits, vegetables and legumes. Additional components included: low to moderate red wine consumption; high consumption of whole grains and cereals; low consumption of meat and meat products and increased consumption of fish; moderate consumption of milk and dairy products. The control group was no intervention or minimal intervention, usual care or another dietary intervention. We found 30 RCTs (49 papers) that met these criteria. The trials varied enormously in the participants recruited and the different dietary interventions. We grouped studies to look at the effects of following a Mediterranean-style diet into the following four categories to help us with our interpretation of the results: 1. Mediterranean dietary intervention compared to no intervention or a minimal intervention to prevent the onset of cardiovascular disease; 2. Mediterranean dietary intervention compared to another dietary intervention to prevent the onset of cardiovascular disease; 3. Mediterranean dietary intervention compared to usual care for people with cardiovascular disease to prevent recurrence; 4. Mediterranean dietary intervention compared to another dietary intervention for people with cardiovascular disease to prevent recurrence. Few trials reported on the occurrence of cardiovascular disease either in those with or without disease to begin with. A large trial in people at high risk of cardiovascular disease found a benefit of the Mediterranean dietary intervention compared to a low-fat diet on the risk of having a stroke, but not on heart attacks, death from heart disease or other causes. A further study in people with cardiovascular disease found a benefit of the Mediterranean dietary intervention on death from heart disease or other causes. We rated these two studies as providing low to moderate-quality evidence. We had to exclude two studies from our analyses as concerns had been raised that the data were unreliable. The other trials in the review measured risk factors for cardiovascular disease. There was low to moderate-quality evidence for some beneficial changes in lipid levels and blood pressure with a Mediterranean-style diet in people without disease. In people with cardiovascular disease already there was very low to low-quality evidence that there was no effect of a Mediterranean-style diet on risk factors. Two trials reported side effects of the diet that were either absent or minor. The review concludes that, despite the large number of included trials, there is still uncertainty regarding the effects of a Mediterranean-style diet on cardiovascular disease occurrence and risk factors in people both with and without cardiovascular disease already. We did find seven studies that are still ongoing and when we have the results from these we will incorporate them into the review to help reduce the uncertainty.
On 26 November 2013 we performed searches to look for clinical trials where lamotrigine was used to treat neuropathic pain or fibromyalgia. We found 12 studies of reasonable quality that tested lamotrigine against placebo for a number of weeks. Almost half of the 1511 people in the studies had painful limbs because of damaged nerves caused by diabetes, and seven different painful neuropathic conditions were examined. No studies looked at fibromyalgia. Lamotrigine did not help the pain, and was no different from placebo except in causing more side effects. Adverse events were more frequent with lamotrigine than placebo, with rash in 1 person in 27.
Pre-eclampsia, also known as toxaemia, is a condition which leads to high blood pressure and protein in the urine. Eclampsia is when a pregnant woman with pre-eclampsia has one or more seizures (fits). Eclampsia is a serious threat to the life of both mother and baby. We identified three randomised trials, involving 397 women with eclampsia who were randomly assigned to treatment with magnesium sulphate or a lytic mixture of chlorpromazine, promethazine and pethidine that lowers blood pressure and is a sedative. Both drugs could be given either by intravenous or intramuscular injection. Although the trials were small and of average quality, the review found that magnesium sulphate was better than lytic cocktail at preventing maternal deaths, further seizures, and breathing problems and coma for the mother. Magnesium sulphate is also relatively cheap and easy to use. The adverse effects of magnesium sulphate come largely from its smooth muscle relaxant activity; respiratory depression is dose dependent and, with monitoring of the woman's clinical condition, uncommon.
The quality of evidence from this review was assessed as being very low quality due to the small number of studies, risk of bias in the included studies (in particular, high proportions of participants dropped out) and the fact that many studies excluded women with chronic (i.e. long lasting) or severe depression, or both. We were able to combine data from three studies comparing a type of commonly used antidepressant called selective serotonin reuptake inhibitors (SSRIs) with placebo. The results showed that women with postnatal depression who were given SSRIs were more likely to improve or recover than those given placebo. We were unable to combine the data from studies comparing antidepressants with other treatments or treatment as usual due to the very small number of studies identified for these comparisons. There was insufficient evidence to conclude whether, and for whom, antidepressant or psychosocial/psychological treatments are more effective, or whether some antidepressants are more effective or better tolerated (or both) than others. Conclusions were also limited by the lack of data on long-term follow-up, the safety of breastfeeding or child outcomes. Larger studies need to be done, and treatment decisions for women with postnatal depression will need to use evidence from other sources such as trials in general adult populations and observational studies of antidepressant safety in the postnatal period. The review authors recommend that future studies in this area should include women with severe postnatal depression, long-term follow-up on psychiatric symptoms and quality of life in mothers who have been treated for postnatal depression. In addition, more evidence is needed on outcomes for infants, particularly with regards to the safety of breastfeeding and effect of treatment for postnatal depression on the maternal-infant relationship.
Twenty-six studies (including 14,939 people with moderate to severe symptoms of COPD) compared twice-daily salmeterol or formoterol with a dummy inhaler. The evidence gathered for this review is current up to June 2013. Results within studies were described most often after six months of treatment, but some were reported at three months and others after as long as three years. More men than women took part, and they had moderate to severe symptoms when they began treatment. People who took LABA inhalers showed greater improvement on quality of life scales than those taking dummy inhalers, and they had fewer serious flare-ups that resulted in a hospital stay (18 fewer per 1000). They also had better lung function than people who had taken placebo. LABA inhalers did not reduce the number of people who died, and no significant difference was noted in the number who had serious adverse events while taking the medication. These studies were most often sponsored by drug companies and were generally well designed. People in the studies did not know which treatment they were getting, and neither did the people doing the research. Several studies did not describe flare-ups, hospital stays or lung volume, so there is a chance that evidence obtained in future studies would change the strength of what has been concluded. Additionally, quite a lot of variation was noted between studies in the effects of LABA inhalers on quality of life, serious side effects and lung function. This may be explained in part by variation in study methods regarding what medications people could continue to take.
In January and February 2012, we did a computer search for studies of hormones tested for contraception in men. We also looked at reference lists of articles. We considered randomized controlled trials in any language. We wrote to trial authors to find other studies we may have missed. We found 33 studies. The focus of the trials was having no sperm found in semen. The percent of men who achieved no sperm varied widely. We found a few major differences and list them here. 1) Implants plus injected testosterone worked better than a pill plus testosterone patch. 2) Adding a hormone pill improved the effect of testosterone injected weekly. 3) A hormone pill also improved the effect of a testosterone injection with more injections at 6 and 12 weeks. 4) A lower dose pill did not work as well as a higher dose when testosterone was put under the skin (implant). 5) When used with implants, a lower dose of injected testosterone led to no sperm more often than a higher dose. 6) An injected hormone plus injected testosterone led to no sperm more often when given every 8 weeks versus 12 weeks. 7) Four implants of a male hormone worked better than two implants. Several trials showed good results for the percent with no sperm. Five trials studied testosterone and another hormone. The other hormones were desogestrel, etonogestrel, and levonorgestrel. No hormonal birth control for men is ready for general use. Most trials were small pilot studies trying out different hormone treatments. Larger trials with better methods are needed to test good leads in this area.
We searched a wide range of electronic databases for studies that randomly assigned children aged six months to 12 years to either zinc supplementation or a control group that did not receive zinc. Eighty randomised studies with 205,401 eligible participants were included in this review. The evidence is current to December 2012. Giving children zinc supplements might reduce their risk of death in general, and their risk of death due to diarrhoea, lower respiratory tract infection (LRTI), or malaria. The quality of evidence for overall mortality was high, though evidence for other critical outcomes was only moderate. Children given zinc experience less diarrhoeal disease than children not given zinc; however, zinc does not seem to reduce children's risk of respiratory infection or malaria. Zinc supplementation may have a very small effect on growth, but eating more calories would probably have a larger effect for many malnourished children. Children who take zinc supplements may experience vomiting as a side effect.
We found 24 studies, which contained information about five different rapid tests. A total of 4271 people participated in these studies. One of the rapid tests (called the rK39 immunochromatographic test) gave correct, positive results in 92% of the people with visceral leishmaniasis and it gave correct, negative results in 92% of the people who did not have the disease. This test worked better in India and Nepal than in east Africa. In India and Nepal, it gave correct, positive results in 97% of the people with the disease. In east Africa, it gave correct, positive results in only 85% of the people with the disease. A second rapid test (called latex agglutination test) gave correct, positive results in 64% of the people with the disease and it gave correct, negative results in 93% of the people without the disease. For the other rapid tests evaluated, there are too few studies to know how accurate they are.
We searched scientific databases for clinical studies (randomised controlled trials and well-designed non-randomised studies) of people of any age with bone marrow disorders and a low platelet count. The evidence is current to 12 October 2017. One study was eligible for inclusion in the review. This study was stopped after recruiting only nine participants because it had taken three years to recruit the nine participants (the study had planned to recruit 60 participants in two years). We found no ongoing studies. The only included study in this review did not report any outcomes. We found no evidence to help us decide whether giving platelet transfusions to treat bleeding is as good as giving platelet transfusions when the platelet count is below a prespecified level. There is an urgent need for good-quality studies to answer the questions of this review. We did not assess the quality of the evidence because no data were available from the one included study.
The review authors searched for randomized controlled trials in which supplementation with the antioxidant vitamins beta-carotene (provitamin A), vitamin C and vitamin E was compared to inactive placebo or no supplement. Nine trials involving 117,272 adults of age 35 years or older were included in this review. The trials were conducted in Australia, Finland, India, Italy, the United Kingdom and the United States and were of high methodological quality. The doses of antioxidants given in each trial were higher than the recommended daily allowances. The trials provided no evidence of effect of the antioxidant vitamins beta-carotene, vitamin E and vitamin C given alone or in combination on the incidence of cataract, its extraction or progression and on the loss of visual acuity. Some participants (7% to 16%) on beta-carotene developed yellowing of the skin (hypercarotenodermia).
During the last two decades, doctors have been looking for the best treatment to prevent clots in the coronary arteries of patients with coronary heart disease. This review summarises the results of 60 studies which used a potent class of intravenous antiplatelet drugs - glycoprotein IIb-IIIa blockers - in 66,689 participants. This treatment was tested in two different conditions: in patients undergoing coronary angioplasty (inserting a deflated small balloon in the artery and expand it to open the vessel) with or without inserting a stent (a thin metal expandable tube or sleeve to scaffold the artery open); and as the initial treatment of patients hospitalised for unstable angina and non-ST segment elevation acute myocardial infarction (prolonged coronary chest pain with or without small myocardial infarction). The evidence is up to date as January 2013 and the overall quality of the body of evidence was good. Overall, the use of these drugs during coronary angioplasty with or without inserting a stent reduced the risk of death at 30 days, and the risk of death or myocardial infarction at 30 days and at six months. The results were similar for stable and for unstable patients with coronary artery disease, but there was comparatively less benefit for patients previously treated with clopidogrel, an oral antiplatelet drug. On the other side, these drugs only slightly reduced the risk of death or myocardial infarction when administered as initial medical treatment in patients with unstable angina or non-ST-elevation myocardial infarction. The benefits of glycoprotein IIb/IIIa blockers need to be balanced against the increased risk of bleeding.
In a search up to 1 June 2018, we identified three completed studies involving 161 preterm infants admitted to a neonatal intensive care unit (NICU) at a tertiary hospital. One study involved 51 preterm infants, and each infant had an equal chance of being chosen to receive either treatment (a randomised controlled trial). One study involved 80 preterm infants who were sequentially assigned to control and treatment groups (a quasi-randomised trial). One study was a prospective randomised trial involving 30 infants, but the way it was reported meant there was not enough information for us to include in our analyses. We found that exposure to the smell and taste of milk with orogastric or nasogastric tube feedings had no clear effect on the time to reach full sucking feeds. One study reported no adverse effects. Exposure to the smell and taste of milk also had no clear effect on time to reach full tube feeding, feed tolerance, incidence of late infection and severe intestinal infection, duration of intravenous nutrition, and growth. Very low-quality evidence from two studies suggested that exposure to the smell and taste of milk decreased the length of hospital stay by almost four days compared to no exposure to the smell and taste of milk. However, the included studies were small and had several limitations in terms of how they were done. Exposure to the smell and taste of milk with orogastric or nasogastric tube feedings may decrease length of hospitalisation for preterm infants. However, the effect of this treatment to accelerate feeding in preterm infants is uncertain due to limited and very low-quality evidence. Future research needs to explore the effect of exposure to the smell and taste of milk with tube feedings on important clinical outcomes, such as time to full sucking feeds, adverse effects, time to reach full tube feedings, feed tolerance, incidence of infection, and growth.
We searched medical databases for clinical trials comparing giving a statin to giving a placebo (pretend medicine) to people with normal cognitive function (which is brain activities that allow us to gain and use knowledge) and of sufficient age to be at risk of Alzheimer's disease. We found two suitable randomised trials for inclusion in this review with 26,340 participants; neither showed any reduction in occurrence of Alzheimer's disease or dementia in people treated with statins compared to people given placebo. Side effects were low in both statin and placebo groups with no difference between groups in the risk of dropping out of the trial due to side effects. There were limitations in the included studies involving the methods of assessment of cognition and the inclusion only of participants deemed to be of moderate to high risk of a problem with their blood (vascular) system. Nevertheless, there was good evidence that statins given in late life to people at risk of vascular disease do not prevent cognitive decline or dementia.
We found eight studies including 250 participants in a search of the available studies up to 1 July 2016. All of the studies took place in a hospital. The primary outcomes of the review showed no difference between the inhaler with a spacer and the nebuliser. However, in our secondary outcomes, we found some evidence that nebuliser treatment improves lung function more than inhalers with a spacer, but the quality and quantity of the data is limited. We found no difference between the therapies in terms of side effects or for reducing breathlessness. There are no studies available testing dry powder inhalation against a nebuliser. Due to the low quality and quantity of the data, it is not clear whether nebulisers or inhalers with spacers are better for lung attacks. We found no difference between an inhaler with a spacer and the nebuliser in lung function after one hour or in unwanted side effects during lung attacks of COPD. The secondary outcome for lung function did favour nebulisers over inhalers with a spacer.
There are a number of studies that suggest a relationship between decline of melatonin function and the symptoms of dementia. Meta-analysis was conducted on data from three randomised, placebo controlled trials that were designed to evaluate melatonin for managing dementia-related cognitive changes; data also were pooled from two of these trials that evaluated melatonin for managing mood and behavioral disturbances. Significantly improved outcomes were found from the meta-analysis of psychopathologic behavior and mood scale scores. Melatonin treatment may be effective for the treatment of dementia-related psychopathologic behavior disturbances. No evidence was found to support the effectiveness of melatonin for the treatment of cognitive impairment.
The review of trials found that both were similarly effective in relieving exercise-induced asthma for both children and adults. More people have sore throats and an unpleasant after-taste after using nedocromil sodium.
We searched for studies up to August 2019. We included 10 studies with a total of 993 patients comparing fibrinolytics with a placebo and compared these to look for differences. We also included two studies comparing different fibrinolytics with a total of 149 patients and compared these separately. We found some low-certainty evidence that fibrinolytics moderately reduced the need for surgery. There was no clear evidence that fibrinolytics changed the risk of death. There was some low-certainty evidence which showed that there may be a risk of more side effects (mostly bleeding) with fibrinolytics but this is uncertain. We found no clear evidence that any single fibrinolytic was better than another. We considered the certainty of the evidence identified comparing fibrinolytic with placebo to vary from moderate (risk of death) to very low (overall treatment failure). This was mostly due to some studies having one or more domains at high risk of bias as well as concerns that not all studies of this treatment appear to have been published. We considered the evidence comparing individual fibrinolytics to be of low certainty due to not enough patients in the studies as well as one study being at a high risk of bias.
We included 39 studies that involved a total of 2492 adults. The average ages of the participants in the studies ranged from 34 years to 59 years. When reported, most participants had heel pain for several months. Studies were usually conducted in outpatient specialty clinics of hospitals in 17 countries. Steroid injections were usually given with a local anaesthetic agent. Study follow-up was from one month to over two years. The studies compared steroid injection with placebo or no treatment (8 studies); tibial nerve block with anaesthetic (2 studies); heel pads (4 studies); oral anti-inflammatory drugs (NSAIDs) (2 studies); an intensive exercise programme (1 study); shock wave therapy (5 studies); laser (2 studies); radiation therapy (1 study); local NSAID injection (1 study); platelet-rich plasma injections (5 studies); injection of the person's own (autologous) blood (2 studies); botulinum toxin (Botox) injections (2 studies); frozen (cryopreserved) human amniotic membrane injection (1 study); localised peppering involving multiple pricking of the tissues using an inserted needle (1 study); dry needling (1 study); and mini scalpel-needle release (1 study). We also compared different techniques of local steroid injection (5 studies). The eight studies comparing steroid injection with placebo or no steroid injection control provided evidence on heel pain, function, serious adverse events and treatment failure. No studies reported on time to return to work or other activities or short-term adverse events, such as injection-site pain. Steroid injection may slightly reduce heel pain for up to one month after treatment, but not in the longer term including up to six months. We are very unsure whether steroid injection affects longer-term function or reduces treatment failure. There were no serious adverse events, such as infection, reported by these studies. However, these are known to be rare events and we looked at the evidence from all of the studies in the review. Of the 21 studies that reported on adverse events, two studies reported three infections and two ruptures of heel tissues in relation to steroid injection. The evidence for all reported outcomes, including heel pain, for the other comparisons was always very low quality. This means we are very unsure of the results of these trials. There is low quality evidence that local steroid injections may slightly reduce heel pain up to one month but not subsequently. Although serious complications relating to steroid injection were rare, these were under-reported in the included studies and more cannot be ruled out.
We searched for all trials that compared continuous monitoring with intermittent monitoring in people with acute stroke. We identified three studies including a total of 354 participants. Stroke unit care with continuous monitoring was associated with a significant reduction in the chance of being dead or disabled after the stroke. Unfortunately this evidence is not entirely reliable because of the small number of participants, differences in the definitions of abnormal results, and the less reliable methods used in the largest trial. Further research is required to answer many remaining questions, such as when to start continuous monitoring, when to interrupt it, which people should be given priority, and which treatments are most appropriate after the identification of abnormalities in physiological variables.
Four high-quality randomized controlled trials (RCTs; 585 patients) comparing TENS with placebo for chronic low-back pain were included in this study.  Due to conflicting evidence, it is unclear if TENS is beneficial in reducing back pain intensity.  However, there was consistent evidence in two trials (410 patients) that TENS did not improve the level of disability due to back pain. There was moderate evidence that use of medical services and work status (e.g. loss of work, sick days) did not change during treatment. Finally, there did not seem to be a difference between conventional and acupuncture-like TENS. Some adverse effects were reported, typically minor skin irritations observed equally in the treatment and placebo groups. However, there was one participant who developed a severe rash four days after the start of treatment. In summary, the review authors found conflicting evidence regarding the benefits of TENS for chronic LBP, which does not support the use of TENS in the routine management of chronic LBP.
It was not possible to tell whether medication was effective in treating people with anxiety and alcohol use disorders. Although more than twice as many people (57.7%) with social anxiety disorder who were treated with paroxetine in two trials showed signs of clinical improvement compared with people receiving placebo (25.8%), the quality of the evidence was very low. One study reported that buspirone reduced anxiety disorder symptoms after 12 weeks of treatment. None of the other studies found reductions in symptoms. Treatment with medication appeared to be acceptable to participants, but again the quality of the evidence showing this was very low. Certain medication side effects, such as sexual problems, were commonly reported after treatment with paroxetine and sertraline. There was no evidence that treatment had an effect on alcohol use. It was difficult to interpret the findings reported by the studies included in this review. Many participants (43.1% altogether) dropped out of the studies before treatment ended. In addition, outcomes that were reported were either not precise, or appeared to be based on the selective reporting of measures that showed an effect of medication. Funding of two of the studies by drug companies may also have led to reporting of results that favoured the medication.
We found two studies with 89 participants in total. One looked at oral immunotherapy in people with an allergy to apple, comparing it to no treatment, and one looked at sublingual immunotherapy in people with an allergy to peach, comparing it to a placebo. Both studies were in adults. The evidence is current to July 2015. The study of oral immunotherapy for apple allergy found participants who received the intervention were less sensitive to apple than people who did not receive the intervention at eight months. The study of sublingual immunotherapy for peach allergy did not find a difference between the groups in terms of sensitivity at six months. In both studies, there were more side effects in people receiving the treatment, but these were not serious. Overall, the quality of evidence is very low because both studies were small, results were not similar between studies, and there were issues with study design. More research is needed before we can tell if oral and sublingual therapy works for food allergy to fruits.
This review looked at two strategies - steroid avoidance and steroid withdrawal - to investigate their impact on short- and long-term outcomes. These strategies could be used in adults in the first few days after transplantation when used in combination with more powerful immunosuppressive agents. Twenty-one studies were identified and evaluated in this review although only three RCTs enrolling 144 participants met our inclusion criteria. Steroid avoidance and steroid withdrawal strategies in pancreas and pancreas with kidney transplantation were not apparently associated with increased mortality, graft loss or acute rejection, although more studies are needed.
This review compares the efficacy of psychoeducation added to standard care as a means of helping severely mentally ill people with that of standard care alone. The evidence shows a significant reduction of relapse or readmission rates. There seems to be some suggestion that psychoeducation may improve compliance with medication, but the extent of improvement remains unclear. The findings show a possibility that psychoeducation has a positive effect on a person's well being and promotes better social function. In the medium term, treating four people with schizophrenia with psychoeducation instead of standard care resulted in one additional person showing a clinical improvement. The scarcity of studies made the comparison between the efficacy of different formats (programmes of 10 sessions or less or 11 or more, individual or group sessions) weak.
For this updated review (first published in 2003), we searched for randomized and quasi-randomized controlled trials, comparing the success rates of those in a work-based stop-smoking programme with those not involved in a work-based stop-smoking programme. The comparison could be between people within a single worksite, or between one or more worksites randomized to a stop-smoking programme or to no programme (cluster-randomized). The study had to include adults (over 18), and could be in any language and reported in any format, published or not. It had to report the numbers stopping smoking for at least six months. We searched for studies in July 2013, and identified ten new trials that fitted our criteria, making a total for this update of 61 comparisons across 57 included studies. We grouped them into two broad categories: those aimed at helping individual smokers, and those that targeted the workplace environment as a whole. The first group includes such methods as individual or group counselling, self help, nicotine replacement therapy (NRT) and other medications, help from workmates or other staff, and helping quitters to stay smoke-free. The second group includes environmental cues (posters, reminders), financial or material incentives, and comprehensive smoking cessation or health promotion programmes. The review found that programmes based on group behaviour therapy (eight trials; 1309 participants), on individual counselling (eight trials; 3516 participants), on medications (five trials; 1092 participants), and on several interventions combined (six trials; 5018 participants) helped people to stop smoking. The chances of stopping smoking using these methods are about the same in the workplace as they are in other settings. This review found that the following do not help people to stop smoking when delivered in the workplace: self-help methods, support from friends, family and workmates, relapse prevention programmes, environmental cues, or comprehensive programmes aimed at changing several high-risk behaviours. Results were mixed for incentives, with one high-quality trial finding a clear benefit for incentives while the remaining five did not. Earlier studies tended to be less well-conducted and reported than recent ones. Fewer than one in five studies randomized their study population by an acceptable method. Two-thirds of the studies checked the accuracy of those who said they had quit by testing their breath, blood or urine. The results were generally in line with findings from other reviews of those ways of quitting in any setting. The 'Summary of findings' table shows that the trials were generally rated as being of moderate to high quality, further confirming the strength of our findings. Future research might examine what features of the large incentives trial made it more successful than other trials in that group. It would also be helpful to have more trials from developing and low-income countries, where smoking rates remain high and anti-smoking laws are not widely enforced.
Our review of six studies involving 119 participants provided limited evidence that mental practice, when added to traditional physical rehabilitation treatment, produced improved outcomes compared with the use of traditional rehabilitation treatment alone. The evidence to date shows the improvements are limited to measures of performance of real-life tasks appropriate to the upper limb (e.g. drinking from a cup, manipulating a door knob). It is not clear if mental practice added to physical practice produces improvements in the motor capacity of the upper limb (i.e. the ability to perform selected movements of the upper limb with strength, speed and/or co-ordination). Finally, there is no evidence available detailing either the components of the mental practice (e.g. How long should the mental practice sessions be? How many mental practice sessions are necessary?, etc) or the qualities of the survivor of a stroke (How long since onset of stroke? How much recovery is required?, etc) that are required to obtain a positive outcome. However, there is reason for optimism that some of the questions will be answered as there are several large trials currently ongoing.
It has been proven in clinical studies that this 'preoperative' radiotherapy improves the outcome in rectal cancer patients. Recently, several studies have investigated the combination of radiotherapy with chemotherapy (CRT) before surgery. In theory, adding chemotherapy enhances the antitumour activity of radiotherapy. This meta-analysis has summarized the results of five studies that compared preoperative RT alone with preoperative CRT in rectal cancer patients. All of these studies were randomized, which means that the decision to administer either RT or CRT was determined by chance (ballot draw). The results of the meta-analysis may be summarized as follows. Compared to RT alone, preoperative CRT leads to increased side effects during treatment. Also, postoperative complications are somewhat increased, although the risk of dying from postoperative complications is similar. Preoperative CRT is more effective in causing tumour shrinkage (downstaging), and in preventing local recurrence of the disease. However, addition of chemotherapy did not result in more sphincter preserving surgeries, and did not affect the overall survival in rectal cancer patients.
This review of randomised controlled trials showed comparable death and failure rates for oral and intravenous antibiotics for low risk patients, those with solid tumours or chronic leukaemia or lymphoma, and independent of age, source of infection and severity of the neutropenia.
Endometrial (womb) cancer is the most common genital tract cancer in developed countries. Progestagen (a hormone) therapy is sometimes used following initial surgery to reduce the risk of recurrence. However, progestagens have been found to reduce one of the protective factors against heart disease and may also make tumours more resistant to radiotherapy. This review found no evidence to support the use of progestagen as an addition to surgery for newly diagnosed endometrial cancer. Progestagen can, however, prevent or delay recurrence of cancer in some patients.
We searched databases for trials comparing different interventions in adults with symptomatic MPE to April 2015, written in any language. Since we were only interested in rigorously conducted research, we restricted our search to randomised controlled trials (in which participants are randomly allocated to the methods being tested). We analysed the majority of the data using a technique called 'network meta-analysis' which allows lots of different interventions to be compared in one analysis. This analysis ranks the interventions in order of their effectiveness. We found 62 studies involving 3428 patients. In the network meta-analysis, the use of thoracoscopy to remove the fluid and blow talc into the pleural cavity (talc poudrage) appeared to be more effective in preventing fluid build up than a number of other commonly used methods. However, we could not say definitely that it is better than some other methods such as giving talc or doxycycline through a chest drain. Side effects, quality of life and patient satisfaction were reported inconsistently by the included studies, but are important factors to consider when selecting the best management strategy for a patient. There was enough data to perform network meta-analysis for pain, fever and mortality. We found placebo caused the least fever and Corynebacterium parvum (C. parvum) and mepacrine were likely to cause the most. We found no differences in the pain caused by the interventions evaluated. Only one comparison showed a possible difference, revealing that those receiving tetracycline may live longer than those receiving mitoxantrone. As we only evaluated randomised controlled trials, it is possible some harms of treatments were not identified by this review. Many of the studies were of low quality and the characteristics of the individual studies were quite different to each other. This high risk of bias makes it difficult to reach definite conclusions. The available evidence shows that talc poudrage can stop fluid building up. However, we can not be sure that this is definitely the best method, and further research is needed. It is also important to consider global experience of these agents and knowledge of their safety and side effects when selecting the most appropriate pleurodesis method. Indwelling pleural catheters may help improve patient breathlessness, but may be less good at stopping the fluid coming back. Further research is also required to look at particular patient groups and explore patient-centred outcomes, such as breathlessness and quality of life in more detail. Ideally a fuller understanding of the potential harms of the treatments from the patients' perspective would also be beneficial.
This review was designed to look at whether there is evidence to show if this is true or not. At the moment there is only one randomised controlled study, which involved 256 women. This study does show a lower rate of gestational diabetes mellitus in women who took probiotics from early pregnancy, with the rate of diagnosis of gestational diabetes mellitus being reduced by two-thirds and their babies on average weighed 127 g less at birth. This study did not find differences in the rates of miscarriage, intrauterine or neonatal death or stillbirth. There was no clear evidence of a change in the proportion of women delivered by caesarean section or in the risk of preterm delivery. The study did not report on how much weight the mothers gained during pregnancy or how many babies were large-for-gestational age or that weighed more than 4000 g at birth or on the body composition of the babies. One study is not enough to draw any definite conclusions at the moment. There are other studies underway.
We included eight studies, identified up to October 2013, evaluating the effect of DTIs versus warfarin in people with non-valvular AF. DTIs included were dabigatran 110 mg or 150 mg twice daily (three studies, 12,355 participants), AZD0837 300 mg once a day (two studies, 233 participants) and ximelagatran 36 mg twice daily (three studies, 3726 participants). Of the total number of participants included in this review 61% were men, and the mean age of participants in all studies was over 70 years. Follow-up periods after the end of study medication ranged from zero to four weeks. We conducted the analyses excluding ximelagatran because this drug was withdrawn from the market owing to toxic effects on the liver. We evaluated the effectiveness of the treatment by the number of vascular deaths and ischaemic events. We evaluated safety by the number of (1) fatal and non-fatal major bleeding events, including haemorrhagic strokes, (2) adverse events other than bleeding and ischaemic events that led to treatment discontinuation, and (3) death from all causes. There was no difference in the number of vascular deaths and ischaemic events between all DTIs combined and warfarin, although dabigatran 150 mg twice daily was superior to warfarin for this outcome. Major bleeding events were less frequent with the DTIs, making them a potentially safer alternative to anticoagulation in people at high risk. The adverse events that led participants to discontinue treatment were more frequent with the DTIs. Death from all causes was similar between DTIs and warfarin. We judged the quality of all eight included studies to be adequate to address the main objectives of the review.
This review summarises the evidence from randomised trials on the effects of antioxidants in chronic pancreatitis. Antioxidants are substances that prevent damage to cells caused by toxic byproducts of oxygen in the body. Levels of these byproducts are increased in chronic pancreatitis. Antioxidants constitute a large group that contains many natural and man-made products. Examples include vitamin C, vitamin E, flavonoids (present in tea and cocoa) and many specialised medications. We found 12 randomised trials on this topic. The quality of these trials was mixed, and many had small sample sizes and high rates of dropout. Evidence shows that antioxidants may reduce pain in patients with chronic pancreatitis, but the reported reduction in pain was small. Whether this small decrease really had an impact on patients' complaints is not clear. Given the methodological problems of these trials, a strong conclusion could not be drawn. Use of antioxidants resulted in adverse effects in about 16% of study participants. Most adverse effects were mild, such as headache, nausea and constipation. However, participants who developed these adverse effects tended to stop using antioxidant medication. Other outcomes important for decision making such as use of analgesics, rate of exacerbation of pancreatitis and quality of life, were not very well reported. Therefore, we were unable to reach conclusions on these outcomes.
In this review of studies published up till March 2014, the effectiveness of consultation liaison was compared to standard primary care and other types of mental health care. We included 12 trials with 2605 consumers and more than 905 primary care providers. Consultation liaison was compared to standard care in 11 trials, and compared to collaborative care in one trial. Collaborative care is mental health care co-ordinated by a primary care case manager. There was some evidence that consultation liaison improved mental health, satisfaction with care and adherence to treatment in people with some mental disorders, particularly those with depression, and improved mental health care by primary care providers. There was also some evidence suggesting consultation liaison may not be as effective as collaborative care. However, as the overall quality of trials was low, the effectiveness of these ways of delivering care may have been overestimated. No conclusions can be made regarding the use of consultation liaison with people who have other mental disorders such as schizophrenia or bipolar disorder. There was also no data which could inform practice with specific groups of people such as children and adolescents, and the elderly. More high quality trials of consultation liaison are needed.
Six trials involving 321 infants in three different settings were reviewed. The review was unable to identify clear benefits in outcomes such as duration of hospitalisation or improvement in oxygenation though there were suggestions that some patients may benefit particularly in recurrently wheezy infants treated at home. Well designed studies are required to clarify the role of these agents in young children with wheeze.
In a single large trial of high methodologic quality that involved 300 patients, use of a system (SmartCare™) that automatically adjusted ventilator settings and conducted tests of patients' ability to breathe spontaneously there was no clear benefit of SmartCare™. While it reduced the time to undergo the first test of spontaneous breathing, it did not reduce the time to the first successful spontaneous breathing test compared to a written weaning protocol applied by physicians. There was no clear benefit of SmartCare™ on other clinically important outcomes including the time to successful discontinuation of artificial ventilation , the total duration of mechanical ventilation, the time spent in the intensive care unit and hospital, and the requirement for tracheostomy (an airway inserted into the trachea). Further studies are needed to clarify the role of SmartCare™ in the postoperative setting, in general, and in specific patient populations.
Four randomised controlled trials were identified. In the first one, of 14 participants with moderate or severe myasthenia gravis, the myasthenic muscular score after one month was not significantly different for participants treated with plasma exchange and prednisone than for those treated with prednisone alone but there can be only low statistical confidence in the results of this study because of its small size. A randomised controlled cross-over trial of only 12 participants reported the same efficacy, after four weeks, of plasma exchange or intravenous immunoglobulins for the treatment of moderate to severe myasthenia gravis, but because of bias and a very weak statistical power the data prevent any conclusion. The third, including 87 participants, showed the same efficacy, after two weeks, of plasma exchange or intravenous immunoglobulins for the treatment of myasthenia gravis exacerbation. The fourth randomised controlled trial involving 35 participants reported a benefit from plasma exchange before thymectomy but this trial was heavily biased. No trial addressed the new subtype with antibodies to a muscle specific kinase. Further research is needed to determine the value of long-term plasma exchange for treating myasthenia gravis and to compare plasma exchange with alternative short-term treatments for myasthenic crisis or before thymectomy in both types of autoimmune myasthenia.
This review assessed whether giving treatment for diseases that present with ulcers in the genital region would reduce sexual acquisition of HIV. Three studies were identified involving 173 HIV-negative patients with genital ulcers. These studies did not provide sufficient evidence that treatment of genital ulcer diseases reduces sexual acquisition of HIV infection. However, genital ulcer diseases are public health problems in their own right and patients with these conditions should be treated appropriately; whether the treatment reduces the risk of HIV infection or not.
We found one small randomized trial in which 34 participants were randomized to receive IVIg or placebo once daily in addition to azathioprine and prednisolone for remission maintenance. This trial did not provide enough evidence to determine if IVIg has an advantage over corticosteroids and immunosuppressants for the treatment of Wegener's granulomatosis.
We searched for clinical trials (up to April 2017) using Cochrane Schizophrenia's specialised register of trials. The review includes three small, short trials published in the 1990s. The trials randomised 47 people with schizophrenia or other chronic mental illnesses who had also developed tardive dyskinesia because they were taking antipsychotic medicines. The treatments the participants received were the calcium channel blockers, flunarizine, nifedipine or diltiazem hydrochloride or placebo (dummy treatment). A small set of very low quality data were available from three small and poorly reported trials. Currently, it is uncertain whether calcium channel blockers are helpful in the treatment of tardive dyskinesia that is caused by taking antipsychotic medicines. Therefore, the use of calcium channel blockers for this purpose remains experimental. Evidence was limited and small scale. It is not possible to recommend these drugs as a treatment for antipsychotic-induced tardive dyskinesia. To fully investigate whether calcium channel blockers have any positive effects, there would have to be more well-designed, conducted and reported clinical trials. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (mcpin.org/).
The evidence is current to January 2014. We identified three eligible studies; two describing 358 ICU patients, and one describing 30 relatives of ICU patients. These were included in the review. The study involving relatives of ICU patients was a substudy of family members from one of the ICU patient studies. All people included in the studies were adults based in Europe and the UK, with a mixed severity of critical illness requiring admission to an ICU. We found no studies that had reported the risk of post-traumatic stress disorder in patients recovering from admission to ICU using a structured clinical interview. The other primary outcome measures of anxiety and depression were described in one study of 36 patients. In this study no clear evidence of a difference was seen in anxiety and depression when patient diaries were used for people recovering from ICU admission, in comparison to no diaries. Post-traumatic stress symptoms in family members and caregivers were reduced in another study of 30 people when patient diaries were used, in comparison to no diaries. Current research has not adequately assessed the safety and effectiveness of patient diaries. Adverse events associated with the use of diaries have not been reported. It has not been established whether patient diaries are an effective practice or whether they may cause harm. The overall quality of the evidence to support the use of diaries to promote recovery for patients and caregivers or families recuperating from critical illness is low or very low. This is because of the small amount of research and the methodological quality of studies. There is no evidence to support their use and it has not been established whether they cause benefit or harm.
The review includes nine randomised clinical trials (RCTs) and a total of 534 participants. The trials originated from six countries. Seven trials included only participants with type 1 hepatorenal syndrome. Two trials included a total of 96 participants with type 1 or type 2 hepatorenal syndrome. Three RCTs reported funding from a pharmaceutical company. The remaining trials did not report funding or did not receive funding from pharmaceutical companies. People who received terlipressin had a lower risk of dying than people who received inactive placebo or no treatment. Terlipressin was also associated with a beneficial effect on renal function. Terlipressin increased the risk of serious circulation and heart problems (so-called cardiovascular events). Other adverse events included diarrhoea and abdominal pain. The analyses mainly included people with type 1 hepatorenal syndrome. No beneficial or harmful effects of terlipressin were found when analysing participants with type 2 hepatorenal syndrome (possibly due to the small number of participants). We considered the evidence to be of low quality.
Cochrane authors included 14 clinical trials (2128 women) evaluating the effects of endometrial injury on outcomes of ART. Thirteen of these trials studied endometrial injury during the menstrual cycle before embryo transfer. One trial studied endometrial injury on the day of oocyte retrieval, which is just a few days before the day the embryo is transferred into the womb. Whether participants had undergone previous embryo transfers varied among the included studies. The evidence is current to January 2015. The included studies suggest that endometrial injury performed sometime during the month before the start of ovarian stimulation as part of ART improves the chances that a woman will achieve live birth and clinical pregnancy. Moderate-quality evidence suggests that if 26% of women achieve live birth without endometrial injury, between 28% and 48% will achieve live birth with this intervention. Contrary to this, endometrial injury performed on the day the eggs are picked up reduces the chances of pregnancy. We are still uncertain about the effect of endometrial injury on adverse events such as miscarriage, multiple pregnancy or vaginal bleeding. However, the endometrial injury procedure does appear to cause some pain, although this is short lived. Evidence that endometrial injury performed in the cycle before ART increases the probability of live birth and clinical pregnancy is of moderate quality. For all other outcomes the evidence is of low or very low quality. The quality of the evidence is reduced because insufficient participants were included in the studies, and because a large proportion of the included studies have important limitations in the methods that they used.
We found six trials published through May, 2013, totaling 208 participants. When women were treated with a course of intensive compression bandaging, their swelling went down about 30% to 37%. When MLD was added to the intensive course of compression bandaging, their swelling went down another 7.11%. Thus, MLD may offer benefit when added to compression bandaging. Examining this finding more closely showed that this significant reduction benefit was observed in people with mild-to-moderate lymphedema when compared to participants with moderate-to-severe lymphedema. Thus, our findings suggest that individuals with mild-to-moderate BCRL are the ones who may benefit from adding MLD to an intensive course of treatment with compression bandaging. This finding, however, needs to be confirmed by further research. When women were given a standard elastic compression sleeve plus MLD and compared to women who received a standard compression sleeve plus a nonMLD treatment, results were mixed (sometimes favoring MLD and sometimes favoring neither treatment.) One-year follow-up suggests that once swelling had been reduced, participants were likely to keep their swelling down if they continued to use a custom-made sleeve. MLD is safe and well tolerated. Findings were contradictory for function (range of motion), with one trial showing benefit and the other not. Two trials measured quality of life, but neither trial presented results comparing the treatment group to the control, so findings are inconclusive. No trial measured cost of care. Trials were small ranging from 24 to 45 participants. Most trials appeared to randomize participants adequately. However, in four trials the person measuring the swelling knew what treatment the participants were receiving, and this could have biased results.
We included 26 randomised controlled studies (involving over 33,000 people) that compared smoking quit rates in people who received text messages or smartphone apps to help them quit, with people who did not receive these programmes. We were interested in studies that measured smoking for six months or longer. We found that text messaging programmes may be effective in supporting people to quit, increasing quit rates by 50% to 60%. This was the case when they were compared to minimal support or were tested as an addition to other forms of stop-smoking support. There was not enough evidence to determine the effect of smartphone apps. Most of the studies were of high quality, although three studies had high drop out rates. We are moderately confident in the results of the text messaging interventions, but there were some issues with unexplained differences between study findings and for some comparisons there was not much data. We have low confidence in the results concerning smartphone apps, and more studies are needed in this field.
We found 3 randomized controlled trials (RCTs) on the use of antibiotics for uncomplicated diverticulitis tested on hospitalised patients. The newest trial investigating the actual need for antibiotics when compared to no antibiotics, a second investigated two different antibiotic cures and a third investigated the length of IV antibiotic treatment. None of the studies found a statistical difference in the tested antibiotic regimes. The newest trial had the overall best quality and had the biggest groups of patients making it the overall best trial. It found no difference in the occurrence of surgery needing complications like abscesses and perforations of the big bowel. Antibiotics can cause serious adverse events for patients like allergic reactions and can even cause other life threatening infections of the bowel. Ultimately, there is a growing antibiotic resistance meaning that the drugs loose their ability to function as bactericidals. This causes limitations in the clinical use of antibiotics when they are needed for treating patients with infections. Therefore there exists strong arguments for limiting the use of antibiotics. The trial that showed no effect of antibiotics is very new and needs confirmation from other similar trials. Ongoing trials will in the next few years be published on the subject.
Three controlled trials that involved a total of 1039 women were reported on between 1922 and 2005. They each used an antiseptic skin preparation and compared perineal shaving with cutting vulval hairs. The overall quality of evidence ranged from very low (for the outcomes postpartum maternal febrile morbidity and neonatal infection) to low (for the outcomes wound infection and maternal satisfaction). When the findings of the trials were combined, no differences were found, with and without shaving, on the number of mothers who experiencing high body temperatures after the birth. One trial also looked at perineal wound infection, the incidence of open wounds and maternal satisfaction immediately after a perineal repair had been completed and found no difference between groups. Most of the side-effects attributable to shaving occurred later, as described by one of the trials. These included irritation, redness, multiple superficial scratches from the razor and burning and itching of the vulva. One trial assessed maternal satisfaction and found no difference between groups. Other outcomes such as pain, embarrassment or discomfort during hair regrowth, were not reported. The present review found no evidence of any clinical benefit with perineal shaving. Not routinely shaving women before labour appeared safe.
This review included 15 studies with 989 participants involving various types of memory retraining techniques, some using computer programs or memory aids such as diaries or calendars. The results of this review showed some evidence to support the use of memory rehabilitation in people with MS. Those participants who had memory rehabilitation had better memory functioning compared to those who did not receive memory rehabilitation, and this difference between groups was found after the intervention was completed and for some time thereafter. However, this outcome was usually measured on assessments that were abstract and did not reflect people’s daily life. Those participants who received memory rehabilitation also showed better quality of life, but this effect was not maintained long term. We also found that those participants who did not receive the memory rehabilitation were better at completing activities of daily living, but these differences between groups were small. The groups who did and did not receive memory rehabilitation did not differ in terms of their subjective reports of memory problems or mood. There are still relatively few large, good-quality studies to base our findings on, so more are needed.
This review aims to determine the effectiveness of long-acting beta-agonists, salmeterol or formoterol, in the treatment of COPD (emphysema/chronic bronchitis). These drugs improve airflow in the lungs, and enable people with COPD to get on with their daily activities. Twenty-four studies (6061 participants) reported the effects of LABAs in people with COPD. People taking salmeterol 50 mcg daily do have fewer exacerbations than those on placebo, and some improvement in lung function and certain quality of life scores. The findings were not consistent enough to support a general recommendation for the use of these drugs in the group of people with COPD with minimal variation in their lung function, although there is some evidence of improvement in important outcomes and these findings require further exploration in additional trials.
The evidence is up to date as of February 2016. We found six trials involving 359,078 adult women and men in Denmark, the Netherlands, Peru, the UK and the United States. Two trials examined the effect of chlamydia screening on levels of chlamydia infection. In the Netherlands, investigators invited women and men aged 15 to 29 every year for three years to have a chlamydia test. In Peru, mobile teams visited 20 cities to offer women sex workers tests for chlamydia over a period of four years. With regard to the level of chlamydia infection, in the Netherlands there was no difference in women and men who had been invited to have yearly chlamydia screening tests compared with women and men who received only one invitation. Only 16% of those invited to be screened had a test in the first year and only 10% had a test in the third year. In Peru, female sex workers in cities with mobile teams had lower levels of chlamydia infection than those in cities without mobile teams. Four trials provided comparable data on PID. The risk of PID was 32% lower in women who were invited to have a single chlamydia screening test than in women who were not invited. When we removed two trials with lower quality evidence, the protective effect of chlamydia screening decreased. I was found no effect on epididymitis in men. The effect of register-based chlamydia screening on C. trachomatis transmission in young adults in the general population is uncertain. We are moderately sure that chlamydia screening can reduce the risk of PID, but we are not sure by how much because of our concerns about quality in some trials.
We included 39 randomised controlled clinical trials (RCTs) with 2599 participants, which we identified in searches up to January 2017. These studies included people of either gender and of all ages, although most studies assessed children who had been told by a healthcare professional that they had eczema. Participants had eczema ranging from mild to severe, and RCTs compared treatment with live micro-organisms (probiotics) of varying dose and concentration, taken by mouth, versus no treatment, placebo, or another treatment with no probiotics. The probiotics included were bacteria of the Lactobacillus and Bifidobacteria species taken alone or in combination with other probiotics for a period ranging from four weeks up to six months. We did not look at studies that were seeking to prevent eczema. Most studies were done in Europe, and some were done in Asia, Australia, and New Zealand - all in a medical setting. Most studies were conducted at a single centre. Reviewers applied no language restrictions on study selection. Ten studies were funded by companies supplying the probiotics, and another four studies did not declare the source of funding. Please note that results in this summary are based on the following: a comparison of probiotic against no probiotic; treatment over six weeks to three months, except for the investigator-rated eczema severity outcome, for which participants were treated longer (16 weeks); and outcomes measured at the end of the treatment period, apart from adverse events, which were assessed throughout treatment. Unless otherwise stated, outcomes were measured by participants or parents. The included studies assessed a variety of probiotics of differing concentrations or doses. With regard to score, the higher the score, the more severe were the symptoms. We found that currently available probiotics probably make little or no difference in reducing eczema symptoms, such as itching and sleep loss (moderate-quality evidence). However, we did find that these probiotics may slightly reduce the severity of eczema scored by patients and their healthcare professionals in combination (low-quality evidence), although it is uncertain if such a change is meaningful for patients. In terms of patient quality of life, we found no evidence that probiotics make a difference (low-quality evidence). We found no evidence of an increase in adverse events; those reported in included studies that were related to treatment were tummy and gut upset with diarrhoea, constipation, vomiting, and colic pains (low-quality evidence). Analysis suggests that further probiotic studies assessing the effects of eczema symptoms may not be worthwhile, as they are unlikely to change the outcome at the end of active treatment. The quality of evidence supporting our key findings was low, apart from one moderate rating for participant-rated symptoms of eczema. Reasons for this include variability between studies, which could not be explained, and not enough available data.
We included 43 studies that compared prokinetics with either placebo (powder that has the appearance similar to drug) or another prokinetic for treatment of functional dyspepsia. The studies were limited to those which assessed only adults who presented with upper abdominal discomfort but who did not have a specific cause after investigation. We are uncertain whether prokinetics reduce dyspeptic symptoms, compared to no prokinetic treatment. We are also uncertain which prokinetics had the most efficacy in reducing dyspeptic symptoms, improving post-treatment symptom scores, or improving the mean difference of symptom score. We are uncertain whether prokinetic treatment can improve quality of life. We are uncertain whether prokinetics (except cisapride) differ from no prokinetic in producing unpleasant symptoms. The most common unpleasant symptoms from prokinetics were diarrhoea, abdominal discomfort and nausea. The quality of the evidence was graded as low or very low. We need more research to prove the benefit of prokinetics for treatment in people with functional dyspepsia.
We searched the scientific literature for all randomised trials published up to May 2015 and found only two trials to include in the review. The trials recruited a total of 83 boys (6 to 13 years of age) who were treated for a maximum of one year. We found no clear evidence of important differences in verbal and non-verbal intellectual functioning between treatment with LAC and placebo. Regarding hyperactive behaviour, teachers' assessments found no clear evidence of differences between treatment with LAC and placebo. Parents' assessments showed some differences between treatments favouring LAC, but changes were not large enough to be considered clinically relevant. Only one study assessed social skills, and it reported no clear evidence of a difference between LAC and placebo in adaptive behaviour, though results in the socialisation domain favoured LAC. No side effects were reported, and no study reported on the secondary outcome of caregiver burden. The available evidence is of low quality. Risk of bias for these studies is unclear regarding the procedures used to randomise participants to LAC or placebo, to conceal treatment allocation, and to blind assessors to the results of the treatments. At least one of the studies was funded by a drug manufacturer with a commercial interest in the results. One of the studies was also funded by charitable monies.
Study characteristics: This updated Cochrane review included 17 studies involving 2434 critically ill men and women who were being cared for in medical, surgical, neurosurgical and mixed medical/surgical intensive care units (ICUs). The studies compared the use of protocols to wean patients from the ventilator against usual practice. They were conducted in ICUs in America, Europe, Asia and Australia. The ICUs cared for patients with heart conditions, breathing difficulties, head injuries, trauma and following major surgery. In 13 studies, clinicians used weaning protocols to guide them to reduce the ventilator support. In four studies ventilator support was reduced automatically by programmed computers following a protocol. Results: In comparison with usual practice without protocols, the average total time spent on the ventilator was reduced by 26%. The duration of weaning was reduced by 70% and length of stay in the ICU reduced by 11%. Using protocols did not result in any additional harms. We found considerable variation in the types of protocols used, the criteria for considering when to start weaning, the medical conditions of the patients and usual practice in weaning. This means that we cannot say exactly which protocols will work best for particular patients, but we do know they have not been beneficial in neurosurgical patients. Quality of evidence: We graded the quality of the available evidence as moderate for duration of ventilation and harmful effects, and low for the duration of weaning and ICU length of stay. The reasons for our grading were that results were not consistent across the studies, and studies lacked sufficient detail about usual care practices.
For this systematic review, we identified six trials conducted in Denmark, Germany, India, Japan, United Kingdom, and United States, which included 750 participants. These trials compared corticosteroid treatment with placebo or another treatment; they varied in the way corticosteroids were given and the dose. Two trials compared oral corticosteroids versus placebo; three trials compared intravenous corticosteroids versus placebo; one trial compared two types of intravenous corticosteroids; and one trial with three groups compared oral corticosteroids versus intravenous corticosteroids versus placebo. Participants in all six trials were followed up for at least three months. Outcomes of visual acuity, contrast sensitivity in the normal range and visual field were assessed at 1, 6, and 12 months. Quality of life also was assessed and reported in one trial. The information is current as of 7 April 2015. There was no available evidence of beneficial effect from oral or intravenous corticosteroids compared with placebo for the visual acuity, visual field, and contrast sensitivity outcomes. Adverse effects, although not consistently reported, included dermatological symptoms, endocrinological disorders, gastrointestinal problems, headache, fever, sleep disturbance and psychiatric problems. Severe adverse events were reported in the intravenous steroid treatment group of one trial. The investigators of three trials concluded that minor adverse events were more common in steroid groups than in the placebo group. Out of six trials included in this review, we assessed one trial to have high risk of bias due to including a subset of participants who were allowed to choose their intervention. The remaining five trials were of either low or uncertain risk of biases.
We included two trials (144 total participants) in this review. Participants included men and women, most of whom were older than 50 years, who had good visual acuity. Participants were either susceptible to or had been diagnosed with an early stage of AMD. Both trials compared simvastatin with placebo. The larger trial, with 114 participants and conducted in Australia, used a higher dose of 40 mg per day and had a treatment period of three years. The smaller trial, with 30 participants and conducted in Italy, used a lower dose of 20 mg per day and had a treatment period of three months. The evidence provided in this review was up-to-date as of March 2016. Neither trial provided sufficient evidence to determine whether statins are effective in delaying the onset or progression of AMD. Information was lacking for outcomes related to vision, quality of life, and adverse events. The overall quality of the evidence was low. In the smaller trial, the number of participants enrolled and the short treatment period may not have been sufficient for detecting the effect of statins on AMD, which develops over time. In the larger trial, 30% of participants did not attend the three-year follow-up visit, and the amount of missing data hindered our ability to draw any reliable conclusions for this trial.
This review assessed evidence from 1509 participants in 15 randomised, double blind, placebo-controlled clinical trials of naproxen or naproxen sodium (a non-steroidal anti-inflammatory drug) in adults with moderate to severe acute postoperative pain. At doses equivalent to 500 mg and 400 mg, orally administered naproxen provides effective analgesia. About half of those treated experienced at least half pain relief over four to six hours, and the effects lasted, on average, up to nine hours. Associated adverse events did not differ from placebo, but these studies are of limited use for studying adverse effects.
We performed a comprehensive literature review and identified six randomized controlled trials (an experiment in which participants are randomly assigned to receive two or more interventions and the results are compared) that involved a total of 326 participants. Four of the six studies assigned patients who had been receiving azathioprine alone to either continue or discontinue therapy (215 participants). Two of the six studies assigned patients who had been receiving azathioprine in addition to infliximab to continue therapy or discontinue azathioprine (111 participants). Clinical relapse occurred in 13% (14/104) of patients who continued azathioprine monotherapy compared to 32% (36/111) of patients who discontinued azathioprine monotherapy. No differences were observed for Crohn's disease-related complications, side effects, serious side effects and withdrawal due to side effects. Common side effects included infections, mild decrease in the number of white blood cells, abdominal symptoms, joint pain, headache and elevated liver enzymes. Among patients who continued combination therapy with azathioprine and infliximab, 48% (27/56) had a clinical relapse compared to 49% (27/55) of patients discontinued azathioprine but remained on infliximab. No differences in side effects, serious side effects or withdrawal due to side effects were observed. Common side effects reported in the combination therapy studies included infections, liver test elevations, joint pain and infusion reactions (a hypersensitivity reaction to the biologic medication). Overall, the quality of evidence for each outcome was low due to a high risk of study bias and small numbers of patients evaluated. The effects of withdrawal of immunosuppressant therapy in people with Crohn's disease in remission are uncertain. Low quality evidence suggests that continuing azathioprine monotherapy may be superior to withdrawal of azathioprine for avoiding clinical relapse in people with Crohn's disease in remission. Low quality evidence suggests that stopping the immunosuppressive after combination therapy does not seem to impact on the risk of relapsing. It is unclear whether the withdrawal of azathioprine, initially administered alone or in combination, impacts on the development of Crohn's disease-related complications, side effects, serious side effects, or withdrawal from the studies due to side effects. Additional research is needed in this area to better inform clinical practice, particularly high-quality randomized controlled trials examining outcomes when biologic therapy is withdrawn.
We found eight clinical studies in October 2014, that examined the blood pressure lowering effect of carvedilol and labetalol in 1493 participants with high blood pressure. These people were randomly assigned to receive either a fixed dose of dual receptor blockers or a placebo for 3 to 12 weeks. On average, dual receptor blockers lowered systolic BP by six points, diastolic BP by four points and heart rate by five beats per minute in patients with mild to moderate high blood pressure. There were more data on the effects of carvedilol. On average, carvedilol lowered systolic BP by four points and diastolic BP by three points. Higher doses of dual receptor blockers caused more slowing of heart rate but not more lowering of BP. The BP lowering effect of dual receptor blockers was less than other classes of BP lowering drugs. Patients taking dual receptor blockers were not more likely to withdraw from the study compared to patients taking placebo. The quality of the evidence was judged to be low due to various types of bias that could exaggerate the effect. A low quality of evidence means future research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
We searched the literature for studies that looked at the effects of restricting salt in the diets of people with CKD up to January 2015. We found eight studies that involved 258 people which met our inclusion criteria. Study participants included people in the early stages of CKD (six studies), who were on peritoneal dialysis (one study), or were kidney transplant recipients (one study). The average study duration was six weeks, and ranged from one to 26 weeks. We did not find any studies that measured the effect of salt intake on the incidence of death, heart disease, or need to begin dialysis. We found that reducing salt intake reduced 24 hour sodium excretion, blood pressure. One study reported restricting salt intake reduced the risk of oedema (swelling). Antihypertensive medication dosage was significantly reduced with a low salt diet. There was no significant difference in kidney function measures or body weight. There was no significant change in total cholesterol or hypotension. Long-term effects of salt restriction in people with CKD is lacking that meant we were unable to determine the direct effects of sodium restriction on primary endpoints such as mortality and progression to end-stage kidney disease (ESKD). Research into the long-term effects of sodium-restricted diet for people with CKD is warranted, as is investigation into adherence to low salt diet.
We assessed evidence on the following outcomes: 1. Nausea, vomiting, cramping abdominal pain, bloating, abdominal distension, wound complication, deep venous thrombosis, urinary tract infection, pneumonia. 2. Time to first: bowel sound, gas, stool, start of regular diet. 3. Length of hospital stay Early feeding was defined as having fluids or food within 24 hours of surgery. Delayed feeding was defined as having fluids or food 24 hours after surgery, and only if there are bowel sounds, passage of gas or stool, and a feeling of hunger. The evidence is current to April 2014 We included five published studies of 631 women, mainly with gynaecologic cancer. Recovery of bowel function was faster in those with early feeding. There was no difference in rates of nausea or vomiting, abdominal distension, need for a postoperative nasogastric tube or time to first bowel movement, but early feeding was associated with a shorter time to bowel sounds and onset of gas. The early feeding group resumed a solid diet 1½ days sooner than those having delayed feeding and the hospital stay was one day shorter. Also, the early feeding group were more satisfied with the feeding schedule, although only one study reported this. Early feeding appeared safe, without increased postoperative complications and with fewer infectious complications overall. Most of the evidence was moderate quality. The main limitation was lack of blinding, which could influence the findings for subjective outcomes such as self-reported symptoms, hospital stay, patients' satisfaction and quality of life. The evidence suggests that eating and drinking on the first day after abdominal gynaecologic surgery is safe and could reduce the length of hospital stay.
We found no randomised controlled trials, and identified only one non-randomised study published 30 years ago, on this topic. This study included 77 participants who had stomach ulcer and in whom medical therapy had failed after an average treatment duration of 29 months. Medical therapy included histamine H2 receptor blockers (medicines that block the action of the chemical histamine, resulting in a decreased production of stomach acid, such as ranitidine), antacids, and diet. It must be highlighted that this form of medical treatment is not considered to be as effective as treatment with proton pump inhibitors. The authors do not state whether these were recurrent or refractory ulcers. Of the 77 included participants, 37 participants continued to have medical therapy, while 40 participants received surgical therapy. Whether to use medical or surgical treatment was determined by participant's or treating physician's preference. The evidence is current to September 2015. The study authors reported that two participants in the medical treatment group (5%) had stomach cancer, which was identified after repeated examinations using a camera to look inside the body (an endoscope), in this case, the stomach and small intestine. They did not report the percentage of participants who had stomach cancer in the surgical treatment group. They also did not report the implications of the delayed diagnosis of stomach cancer in the medical treatment group. They did not report any other outcomes of interest (measures by which one treatment can be considered better than another) for this review (that is health-related quality of life, treatment-related complications, peptic ulcer-related complications, abdominal pain, and long-term deaths). There is thus no study that provides the relative benefits and harms of medical versus surgical treatment for recurrent or refractory peptic ulcers. Studies on this topic are urgently required. Since the only study that compared medical and surgical treatment in people with refractory or recurrent ulcers did not report any of the outcomes in a sufficiently detailed manner, we were not able to assess the quality of evidence in a formal way.
Azathioprine is a drug that suppresses the immune system. This review includes three trials with a total of 81 patients. Forty patients were given azathioprine and forty-one were given placebo. Patients taking azathioprine had lower tender joint scores when compared to patients taking placebo. Significantly more patients in the azathioprine group withdrew from the studies due to adverse reactions compared to patients in the placebo group. This evidence is based on a small number of patients in older trials. These findings suggest that several other drugs should be used before considering azathioprine for a patient with rheumatoid arthritis.
The review aimed to look at the evidence from studies testing the use of ultrasound in clinical practice. Six trials were included in the review. Poor reporting of trial methods made it difficult to assess the risk of bias of the included studies. The six trials involved a total of 606 participants with acute ankle sprains of relatively short duration. Five trials compared ultrasound therapy with sham ultrasound (machine turned off). Three of the six trials included single comparisons of ultrasound with three other treatments. The main results were from the review of the five placebo-controlled trials (sham ultrasound). These found that ultrasound therapy does not seem to enhance recovery or help to reduce pain and swelling after an ankle sprain, or improve the ability to stand on the affected foot and ankle. Most ankle sprains heal quickly. While ultrasound may still improve recovery in a small way, this potential benefit is probably too small to be important.
Infant health may also be poor, primarily due to premature birth and growth restriction.This review examined the effect of treating women with HELLP syndrome using corticosteroids (which can reduce inflammation). The results of this review did not indicate that there was a clear effect on the health of pregnant women when treated with corticosteroids, or their babies. Corticosteroids did appear to improve some components of the women's blood tests, but it is not clear that this had an effect on their overall health. The review identified 11 randomized controlled trials involving 550 women that compared corticosteroid (dexamethasone, betamethasone, or prednisolone) given during pregnancy, just after delivery or in the postnatal period, or both before and after birth, with placebo or no treatment. Two further trials showed that there was no clear difference between dexamethasone and betamethasone on the substantive clinical outcomes for women or their infants. Dexamethasone did improve maternal platelet count and some biochemical measures to a greater extent than betamethasone.
This systematic review investigated different ways to manage such sexual dysfunction. We included 23 randomised studies, with a total of 1886 participants who had developed their sexual problems while taking antidepressant medication. Twenty-two of these studies looked at the addition of further medication to the ongoing treatment for depression. For men with antidepressant-induced erectile dysfunction, the addition of sildenafil (Viagra; three studies, 255 participants) or tadalafil (Cialis; one study, 54 participants) appeared to improve the situation. For women with antidepressant-induced sexual dysfunction the addition of bupropion (Wellbutrin, Zyban; three studies, 482 participants) at higher doses appears to be the most promising approach studied so far, but further data from randomised trials are likely to be required before it can be recommended confidently. We did not find evidence that any intervention led to a worsening of psychiatric symptoms; however, we cannot be confident of this for many of the interventions studied, as only small numbers of participants have been studied so far.
This review of trials found that there was insufficient evidence that inhaling corticosteroids as well as taking the drugs orally is better than oral use alone, after emergency department treatment for an asthma attack. There is also insufficient evidence that taking ICS alone is as good as taking them orally, although there is some evidence to support using ICS alone for mild asthma attacks after emergency department discharge. More research is needed.
Until 1 April 2015, we ran computer searches for randomized trials of IUC inserted within 10 minutes of placenta (afterbirth) delivery. We wrote to researchers to find more studies. Trials could compare different times for insertion as well as types of IUC and ways to insert the device. We found 15 trials. Seven recent studies compared IUC insertion right after childbirth versus early insertion (before hospital discharge) or later insertion (weeks after discharge). Four had full reports, although three were small studies. Insertion was as likely to occur when placed right after childbirth as when planned for later placement, except in a study from Uganda. For the four trials overall, the IUC came out more often on its own when placed right after childbirth than when inserted weeks later. Use at six months was more likely with insertion right after childbirth than weeks later. In single studies, the groups did not differ in use at 3 months or 12 months. Eight older studies looked at types of IUC put in right after childbirth. Changing IUC design did not seem to affect whether IUC stayed in or whether it was used later on. Inserting IUC by hand or with a holding instrument did not seem to make a difference. We found newer trials with full reports that compared placement times. The studies were of good quality. Ongoing trials will provide additional data, although some sample sizes are small. Larger studies would provide better information on whether the IUC came out on its own and on whether side effects occurred.
We searched for studies evaluating the effects of nutritional screening as a main intervention in hospital and primary care settings on patient outcomes such as mortality, illness, health related quality of life, and change in BMI or weight. We also searched for studies evaluating process outcomes like identification of patients requiring nutritional care, data recording (e.g. weight and BMI), or referral of patients to dietitians or similar. Three studies met our inclusion criteria, but they were very dissimilar in their design, setting, intervention and outcomes. One study found that primary care physicians were receptive to the intervention but it did not result in any improvement in detection rate and nutritional intervention rate. Two studies were conducted in hospitals: one reported that patients’ weight documentation increased as a result of the intervention, and the other reported significant weight gains and reduction in hospital acquired infection rate in the intervention hospital. Both of these studies suffered from limitations in their design, and it was not possible to rule out the impact of confounding factors on their findings. As a result, we conclude that evidence on the effectiveness of nutritional screening is insufficient. Therefore, further high quality studies should be conducted to assess the effectiveness of nutritional screening programmes in hospitals and communities.
A systematic search of the medical literature found two randomized trials of gabapentin compared with placebo (inactive treatment). The same team of scientists performed both trials, which were sponsored by the manufacturer. The trials involved a total of 355 people with ALS. Treatment with gabapentin lasted six and nine months. We found no trials of baclofen or other GABA modulators in ALS that met our selection criteria. We assessed the gabapentin trials as well run and well conducted. Neither of the trials were long enough to for us to report survival at one year. Combined results from the two studies (based on 274 participants) provided high-quality evidence of little or no difference in estimated one-year survival, the rate of decline in respiratory function, or rate of decline in arm strength in people treated with gabapentin compared to those treated with placebo. One trial (128 participants) measured quality of life and monthly decline in function (measured by the ALS Functional Rating Scale). There was little or no difference in the ALS Functional Rating Scale (ALSFRS) or quality of life between the gabapentin group and the placebo group. People who received gabapentin had more light-headedness, drowsiness, and limb swelling than those taking placebo when we combined data from both trials (353 participants). Fatigue and falls occurred more frequently with gabapentin than with placebo in one trial, but when we combined the data for fatigue from both trials, there was no clear difference between the groups. In conclusion, high-quality evidence indicates that gabapentin does not extend survival or slow the rate of decline of muscle strength or respiratory function. Moderate-quality evidence shows no effect on quality of life or decline in ALSFRS. Other GABA modulators have not been studied in randomized trials. The evidence is current to August 2016.
We included 38 randomised controlled trials involving more than 1900 participants in this review, with 14 trials of chronic ischaemic heart disease, 17 trials of ischaemic heart failure secondary to heart disease, and seven trials of refractory or intractable angina. The mean age of participants ranged from 55 to 70 years, and the proportion of male participants ranged from 51% to 100%. Results indicated that treatment with bone marrow-derived cells can lead to a reduction in deaths in participants followed for at least 12 months. Adverse events occurring around the time of treatment were generally rare. Participants who received cell treatment also experienced fewer heart attacks and arrhythmias when compared to those who received no cells. However, cell therapy does not appear to reduce the risk of rehospitalisation for heart failure or the combined risk of death, non-fatal heart attack, or rehospitalisation, and did not result in any improvement over standard treatment in tests of heart function. These results suggest that cell therapy may be of benefit in people with chronic ischaemic heart disease or heart failure, or both. The quality of the evidence was low, as the number of included studies and participants is not currently high enough to draw robust conclusions. Thirteen studies received commercial funding, of which four were fully commercially sponsored, and 12 studies did not report that participants were blinded to the treatment they received. Further research involving a larger number of participants is required to confirm our results.
Foot ulcers not only lead to physical disability and loss of quality of life but also to economic burden (healthcare costs, industrial disability). The aim is therefore to prevent foot ulcers occurring. This review of high-level studies found that educating people with diabetes about the need to look after their feet seems to improve people's foot care knowledge and behaviour in the short term. There is insufficient evidence that education alone, without any additional preventive measures, will effectively reduce the occurrence of ulcers and amputations.
We found four randomised clinical trials in which 496 adult participants were allowed to receive either a surgical shunt or a radiologic shunt. There were problems with the design of the trials as they had small number of participants and used different shunt types. We judged all four trials at high risk of bias (trials may have overestimated the true effect of shunts treatment). We found no difference in the number of participants who died within 30 days of treatment, and the number that developed encephalopathy (disease of the brain due to toxins bypassing the liver to reach the brain), when surgical shunts were compared with radiologic shunt. We found evidence suggesting more harms with radiologic shunt when we considered the number of participants that died five years after treatment; or had repeat bleeding; or required repeated treatment; or had shunt blockage; that appeared to be more in the radiologic shunt group. Surgical shunts appear to be better than radiologic shunt for treating persistent and repeated bleeding due to varices in people with liver cirrhosis. Given the very low certainty of the evidence due to problems with design of the trials and inadequate number of participants, we are unsure if our conclusion is correct. Future trials with better design and adequate number of participants will likely produce results that are reliable.
We found nine completed trials that compared giving to newborn babies, whose mothers had received opioids during labour, either naloxone or a placebo ('dummy drug'). These trials were conducted more than 30 years ago and they were generally very small including only about 300 infants in total. Most of the trials did not use reliable methods consistently. Evidence is up-to-date as of February 2018. The trials reported the effects of naloxone on the baby's breathing but did not assess the effect on the need for babies to be cared for in a neonatal unit (separated from their mother), whether they needed help with breathing, or on breastfeeding success. None of the trials assessed long-term development. We did not find any trials including babies born to mothers who had used opioids (whether prescribed or non-prescribed) during pregnancy. The available evidence was not sufficient to determine whether giving naloxone to babies whose mothers received opioids during birth was helpful or harmful.
We found no clinical trials with a randomized controlled design that evaluated this topic and measured the number of deaths or any of our secondary outcomes. We identified 73 observational studies that delivered descriptive data on catheter management and survival in people with bloodstream infections caused by Candida. We identified no randomized controlled trials for statistical analyses and assessments. Therefore, we can present no results on the effect of catheter removal on survival when Candida is found in the bloodstream. A total of 73 observational studies reported relevant outcomes after the catheter was removed or was kept in place. In all, 40 studies reported a beneficial effect of catheter removal in patients with candidaemia, and 34 presented results showing no clear differences between groups. No studies reported results in favour of retaining the catheter. We found no reports on the harmful effects of removing a catheter and re-inserting a new catheter. No randomized controlled trials met the inclusion criteria. Consequently, we cannot assess the quality of evidence.
This review found no robust evidence to suggest that combinations of potassium, calcium or magnesium can reduce high blood pressure (BP) in adults. Only three trials assessing a total of 277 participants were found. The only combination assessed by all three trials was potassium and magnesium, demonstrating a statistically non-significant reduction in BP among people receiving this combination. One trial assessed both calcium & magnesium and calcium & potassium and found that neither combination had very much effect on BP. None of the trials were of high quality, so their results may not be reliable. Very few mild adverse effects were reported. These were of short duration and participants did not have to stop taking their treatment.
The researchers identified two randomised controlled trials (total 42 participants) that investigated the role of glutamine for the treatment of active Crohn's disease. One study (18 patients) compared four weeks of treatment with a glutamine-enriched polymeric diet (42% amino acid composition) to a standard polymeric diet (4% amino acid composition) with low glutamine content in paediatric patients (< 18 years of age) with active Crohn's disease. Participants were encouraged to consume the diet orally. If this was not possible the diet was administered via a fine-bore nasogastric tube. The other study (24 participants) compared glutamine-supplemented total parenteral nutrition (TPN) to non-supplemented TPN in adult patients (> 18 years of age) with sudden worsening of inflammatory bowel disease. The TPN diet was administered intravenously via a central catheter (a thin tube) for at least one week. Both studies were generally high quality. Neither study demonstrated any beneficial effects for glutamine. Side effects were not well documented in the two studies. There were no serious side effects noted in the paediatric study. The study in adult patients reported three central catheter-related blood infections in the glutamine group compared to none in the non-glutamine control group. Currently, there is insufficient evidence to allow any firm conclusions regarding the effectiveness and harms of glutamine for the treatment of active Crohn's disease.
We found 18 randomised controlled trials (studies in which participants were randomly assigned to one of two or more treatment groups) involving 1014 infants with infantile colic. The evidence is current to May 2016. Infants were eight to 16 weeks old, and males and females were equally represented. All infants had colic, defined in one of two ways. Some studies defined it as inconsolable crying in otherwise healthy infants, lasting longer than three hours per day for more than three days a week for longer than three weeks. Other studies defined colic as attacks of screaming and crying (usually in the afternoon, or in the early evening) during which the infant failed to respond to any amount of comforting by adults. Four studies explored the effects of simethicone (a drug used to reduce excess gas in the intestinal tract); four studies looked at herbal agents (plant-derived remedies that might have relaxing properties that reduce cramps and pains in the bowel); two studies looked at sugar; and five studies explored the effects of dicyclomine and two the effects of cimetropium bromide (drugs that relieve bowel muscle spasms). One study compared sucrose and herbal tea in a group of infants who received no treatment for colic. Sixteen of 18 studies compared the intervention with a placebo. Among the other two studies, one compared simethicone with Mentha piperita, and the other compared two different dosages of cimetropium. Included studies received funding from different sources: a public institution (two studies), academic funds (one study) and private companies (three studies). Three studies received no funding. Nine studies did not report whether the study received funding. In four studies that reported no funds and no details about funds, private companies supplied the products (pain-relieving agents). Available data provide no evidence that sugar, dicyclomine and cimetropium are effective interventions in the treatment of colic. Some evidence suggests that, compared with placebo or no treatment, herbal agents may reduce crying time. However, because the quality of these studies was very poor and the extent of the benefit observed was variable, these results should be interpreted with caution. The same is true for sugar, dicyclomine and cimetropium, for which we judged the quality of evidence as low or very low. Studies that tested simethicone reported no benefit from administration of this drug over placebo. Two studies reported side effects for dicyclomine, for example, difficulty awakening, wide-eyed state and drowsiness. Studies of other pain-relieving agents reported no side effects as a result of treatment. Low-quality evidence indicates that infants with colic may benefit from treatment with sugar and cimetropium, and that herbal agents may reduce crying time. Moderate-quality evidence suggests that these agents increase the number of children experiencing improvement in symptoms. Overall, evidence is insufficient to allow firm conclusions about the benefits and side effects of the pain-relieving agents examined for treatment of crying due to infantile colic.
We searched scientific databases for clinical trials comparing medication and non-medication-based treatments for epilepsy in people with Alzheimer's disease. We wanted to evaluate how well the treatment worked and if it had any side effects. We included and analyzed one randomized controlled trial (a clinical study where people are randomly put into one or two or more treatment groups) with 95 participants. Concerning the proportion of participants with seizure freedom, no significant differences were found between the antiepileptic drugs (levetiracetam versus lamotrigine, levetiracetam versus phenobarbital, and lamotrigine versus phenobarbital). It seemed that levetiracetam could improve cognition (thinking) and lamotrigine could relieve depression; while phenobarbital and lamotrigine could worsen cognition, and levetiracetam and phenobarbital could worsen mood. The quality of the evidence from the study was very low and results should be interpreted with caution. Large randomized controlled trials, which have a double-blind parallel-group design, are required to determine how effective and well tolerated treatments are for epilepsy in people with Alzheimer's disease. The evidence is current to July 2018.
The review looked at the effectiveness of other drugs that can be taken by mouth. These were drugs that increase blood flow (vasodilators). The evidence from randomised controlled trials is limited. The review authors identified eight controlled studies. These were published between 1980 and 1996 and involved a total of 290 participants randomly assigned to the vasodilator drug or placebo. The length of treatment varied from two weeks to six months. Only two trials looked at the same drug, the angiotensin converting enzyme (ACE) inhibitor captopril so most of the findings were from single trials. Taking enalapril resulted in a small increase in the frequency of attacks in a week. Buflomedil reduced the frequency of attacks but without a clear effect on their severity. Moxisylyte (thymoxamine) also reduced attacks but both beraprost and moxisylyte produced more adverse effects than with placebo. For captopril, beraprost, dazoxiben and ketanserin there was no evidence of an effect on the frequency, severity or duration of attacks. The methodological quality of most trials was poor and they were small. The outcomes were subjective and were reported on scales that were not well described or validated. This makes the clinical importance of the results difficult to assess, especially if the placebo response is high.
This review includes 47 RCTs representing 1,223,856 children. Studies took place in 19 countries: 30 (63%) in Asia, 16 of which were in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. The average age of children was about 33 months. Most of the studies included equal numbers of boys and girls and lasted about a year. The quality of the included studies was variable; however, it was unlikely that death rates were influenced by potential errors in the conduct of the studies. Data on the effect of VAS for the prevention of death were available from 19 of the included studies, and the combined results indicate that vitamin A reduces overall risk of death and death due to diarrhoea by 12%. Vitamin A does not specifically reduce death due to measles, respiratory infections, or meningitis, but it can reduce new occurrences of diarrhoea and measles. Giving oral synthetic vitamin A to children at risk of VAD reduces the risk of night blindness. It also improves levels of vitamin A in their blood. The only reported side effect was risk of vomiting within 48 hours of taking vitamin A in large doses, as recommended by the World Health Organization. We rated the overall quality of the evidence using the GRADE approach, which considers methodological flaws within studies, consistency in reporting of results across studies, extent to which results apply to other settings, and effectiveness of treatments. Based on these criteria, we judged the overall quality of the evidence to be high for benefits of VAS against overall risk of death and death due to diarrhoea. For the rest of the outcomes, we rated the evidence as low or moderate. One large, recently conducted study, which included about 1 million children, did not show any effect of VAS; however, when this study was combined with other, well-conducted studies, VAS still had beneficial effects for the prevention of death and illness. In summary, VAS can reduce risk of illness and death in children aged 6 to 59 months of age who are at risk of VAD.
As of June 2016, we identified 18 randomised controlled trials (a type of scientific experiment in which people are randomly assigned to one of two or more treatments), which included 928 children and adolescents between the ages of 6 and 18 years. These studies compared a range of psychosocial therapy to usual care or some form of non-therapy control (such as education or breathing exercises). We identified four different kinds of psychosocial therapy: cognitive behavioural therapy, hypnotherapy, yoga, and written self-disclosure (a therapy that involves writing down thoughts and feelings about something distressing). The duration of the included studies ranged from five days to three months. The studies were conducted in the USA, Australia, Canada, the Netherlands, Germany, and Brazil. We found that cognitive behavioural therapy and hypnotherapy may be effective in terms of reducing pain in the short term. There was little evidence of long-term benefit. There was no evidence that either therapy had a beneficial effect on quality of life, daily activities, or psychological outcomes such as anxiety and depression. Yoga therapy and written self-disclosure as a therapy had no effect on pain, quality of life, or daily activities. No adverse effects were reported from any of these therapies. We rated the overall quality of the evidence as low to very low for all outcomes. Many of the studies had small sample sizes or weaknesses in their study design. The authors reported no conflicts of interest in relation to funding. Cognitive behavioural therapy and hypnotherapy warrant consideration by clinicians as part of the management strategy for children with recurrent abdominal pain. The overall quality of the evidence was low to very low. More high-quality research is needed to evaluate the particular aspects of the therapies that are effective and to establish whether benefits are maintained over time.
None of the studies focused on participant satisfaction which was our primary outcome. Depending upon the setting of the pulsed dye laser, more than 25% lightening (i.e. by reduction in redness) of port-wine stains occurred. This was after 1 to 3 treatments for up to 4 to 6 months postoperatively in 50% to 100% of the participants of the trials. Substantial evidence is lacking for other laser types and intense pulsed light. Side-effects were rare in the included trials, but 3 trials reported pigmentary alterations in 3% to 24% of the participants, with the highest percentage occurring in Chinese participants with darker skin types. In one study one participant experienced scarring of the skin due to a too-high dose of the laser used. Short-term side-effects included pain, crusting, and blistering in the first two weeks after treatment. Two trials reported no occurrence of long-term adverse effects, i.e. six months after treatment.
We searched scientific databases and internet resources to identify randomised controlled trials (where participants are allocated at random to any dopamine agonist drug or placebo or another type of drug aimed to reduce use of cocaine. We also assessed dropout from treatment and frequency of side effects. We included adults of any gender, age or ethnicity. We included 24 studies with 2147 participants, who were all addicted to cocaine. Most were men (82.%)with an average age of 37 years. The mean duration of the included trials was seven weeks (range 1.5 to 16 weeks) Twenty-two studies were conducted in USA, one in Brazil and one in Spain; all but four were outpatients. The included trials studied the following drugs: amantadine, bromocriptine, L dopa/Carbidopa, pergolide, cabergoline hydergine, and pramipexole. All compared dopamine agonist versus placebo. Four studies compared amantidine versus antidepressants. No differences were found between the drugs and placebo for any of the outcomes considered: dropout (moderate quality of evidence), abstinence (low quality of evidence), severity of dependence (low quality of evidence), adverse events (moderate quality of evidence). Antidepressants was found to be better than the dopamine agonist amantidine for abstinence, but this was based on two studies with very few participants and low quality of evidence. There is no current evidence supporting the clinical use of dopamine agonist medications in the treatment of cocaine misuse. The evidence is current to 12 January 2015.
In April 2016 we searched for reports of clinical trials that used cannabis products to treat symptoms in adults with fibromyalgia. We found two small, moderate quality studies, of four and six weeks long, including 72 participants. Both studies tested nabilone, a synthetic (man-made) cannabis product, comparing it with placebo (a dummy pill) or amitriptyline (an antidepressant frequently used in the treatment of fibromyalgia). Nabilone did not convincingly relieve fibromyalgia symptoms (pain, sleep, fatigue) better than placebo or amitriptyline (very low quality evidence). Compared with placebo and amitriptyline, more people experienced side effects and left the study due to side effects (very low quality evidence). There were no serious side effects reported. We found no relevant study with herbal cannabis, plant-based cannabinoids or other synthetic cannabinoids than nabilone in fibromyalgia. There was not enough high quality evidence available to draw any robust conclusions. We found no studies on medical cannabis in fibromyalgia.
This review aimed to identify all double-blind and single-blind randomized, placebo-controlled trials assessing the effects of ginseng on cognitive function. Five trials investigating the effects of ginseng on healthy participants had extractable information for efficacy and were included in the review. Ginseng appeared to have some beneficial effects on cognition, behavior and quality of life. More rigorously designed studies are needed on this important issue.
This review aims to compare sertindole to the other newer second generation (atypical) antipsychotics in people who have schizophrenia. Two studies were identified which included 508 people. Both compared sertindole to risperidone, were short (12 weeks) and the participants were either at least moderately ill or treatment resistant. There was no overall significant difference between these two medications in terms of improvement in people’s general well-being or their mental state. Also while people on risperidone showed more movement side-effects, those on sertindole were more likely to put on weight, have changes in their heart rhythm and the men were more likely to suffer from sexual dysfunction. The data from these trials are limited and a considerable number of the participants left the study early. In addition, sertindole has only been compared to one second generation antipsychotic and the trials are relatively short. A larger and longer trial comparing sertindole to other second generation antipsychotics, with the outcomes including mental state, general functioning, adverse effects and quality of life, would enhance our knowledge in this area considerably. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).
In this updated review we included 38 controlled trials comparing LOD with medical ovulation induction or comparing different techniques of LOD. The evidence is current to October 2019 Our main analysis with low-quality evidence shows that LOD with and without medical ovulation induction may decrease the live birth rate slightly in women with anovulatory PCOS and CC-resistance compared with medical ovulation induction alone. Analysis including only the higher-quality RCTs shows uncertainty about any difference between the treatments. The evidence suggests that if the chance of live birth following medical ovulation induction alone is 44%, the chance following LOD would be between 32% and 52%. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancies. The evidence suggests that if we assume the chance of a multiple pregnancy following medical ovulation induction alone to be 5.0%, the chance following LOD would be between 0.9% and 3.4%. There may be little or no difference between the treatments for clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. Ovarian hyperstimulation syndrome (OHSS) may occur less often following LOD. The quality of the evidence is not sufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage for the analysis of unilateral LOD versus bilateral LOD. The results of the primary outcomes for the other interventions were insufficient to enable us to draw any conclusions. The evidence was of very low to moderate quality. The main limitations in the evidence were poor reporting of study methods, the presence of bias introduced by the selection of individuals and variability in the results.
Through January 2014, we did computer searches for studies of programs to improve use of dual-methods. We wrote to researchers to find missing data. Studies examined a behavioral intervention for improving dual-method use. The educational program had to address preventing pregnancy and HIV/STI by using condoms plus another modern contraceptive. The intervention was compared with a different program, usual care, or no intervention. We only found four studies to include. Three were randomized trials and the fourth was a pilot study for one of the included trials. The programs differed from one another. They included computer-delivered sessions tailored for each person; phone counseling added to clinic counseling; and case management plus a peer-leadership program. In the latter study, more women in the intervention group reported regular use of dual methods, namely birth control pills plus condoms, than the control group. The pilot study reported a trend toward more regular dual-method use for the intervention group compared to the control group. The other two trials did not show any major difference between the study groups in reported use of dual methods or in test results for pregnancy or STIs. We found few programs to improve use of dual methods, and only one showed an effect. The reports gave enough information on how the interventions were conducted. The studies had adequate follow-up periods of 12 to 24 months. However, the overall quality of results was low, mainly due to study design and losing many women to follow up.
This review identified six randomised controlled trials, including 439 participants, in which a psychological treatment for people with dementia was compared to usual care. Most participants had mild dementia, but one trial was conducted with nursing home residents who had more severe dementia. We found no trials of participants with MCI. The psychological interventions used were based on established psychological models such as cognitive behavioural therapy (CBT), counselling, and interpersonal psychodynamic therapy. In two trials, the psychological treatment was combined with other interventions. We found evidence that psychological treatments can reduce depressive symptoms in people with dementia. There was also some evidence from two trials that CBT may reduce clinician-rated anxiety symptoms in people with mild dementia. Due to the imprecision of our results, we could not tell whether psychological treatments had an effect on patients' quality of life, ability to perform daily activities, overall psychiatric symptoms, or cognition, or on carers' self-rated depressive symptoms, but most studies did not measure these outcomes. Although these results are promising, the small number of studies and the variation between them in the type and duration of treatment make it difficult to draw conclusions about the best way to provide psychological treatment for people with dementia who have symptoms of depression or anxiety. More high quality trials in this area would be beneficial, including trials involving participants with MCI.
We found one trial from the UK, which included 15 participants with delirium. The average age of the participants was 82.5 years; eight participants were male and seven were female. Seven participants also had a history of dementia. This trial compared rivastigmine (a type of cholinesterase inhibitor used in the treatment of dementia) with an inactive treatment (placebo). The trial did not show any difference in effect between those participants given rivastigmine and those given placebo. The study was conducted and reported appropriately, but the small number of participants limits any conclusions that could be made about rivastigmine as a treatment for delirium.
The purpose of this review was to look at whether young people who are part of a restorative justice conference are less likely to reoffend than those who go through normal court proceedings. Four randomised controlled trials were included in this review. Findings indicate that there was no difference between those who are part of restorative justice conferences and those in normal court proceedings in terms of the rate of reoffending after the intervention. There was also no difference between these two groups in terms of a change in their self-esteem or their satisfaction with the process. Results may indicate that victims who are part of a restorative conference are more satisfied than those who are part of court proceedings. The quality of the included studies was low. More high quality research using a design where participants are randomly allocated to an intervention or control group is needed.
Our review includes 20 studies involving 2012 people with ankle sprains. These studies differed from each other in many ways and compared various types of acupuncture with a variety of standard control interventions. Most studies reported only the 'cure rate' - the number of participants who had recovered at a set time. No study reported on patient-reported assessment of function. Only one study reported on adverse events and found skin problems in individuals receiving over-the-counter traditional Chinese herbal patches as a control intervention. Most trials had flaws in the way they were conducted, which makes their results less reliable; for example, most studies failed to ensure participants did not know which intervention they were receiving. One study, which compared acupuncture with no treatment, found more people were cured with acupuncture. Most of the eight studies comparing acupuncture plus another standard treatment versus that standard treatment alone found higher cure rates in the acupuncture group. However, we found that pooling these results did not provide conclusive evidence that acupuncture resulted in a better cure rate. Fourteen studies compared acupuncture with a variety of other non-surgical treatments, such as Chinese herbal patches, hot and cold water, ice packs, Chinese oral herbal medicine and elastic bandages. Some studies found in favour of acupuncture, some in favour of the other treatment and some found a lack of evidence for a difference between the two interventions under test. The pooled results from 11 studies comparing acupuncture versus another non-surgical intervention tended to favour acupuncture, but this evidence was not conclusive. Currently, we are unable to conclude whether or not acupuncture is more effective than other standard methods for the treatment of ankle sprains in adults because of the very low quality of the available evidence. Because the adverse effects of acupuncture treatment were not described in most of the studies, we are also unable to draw any conclusions about the safety of acupuncture. Large, high quality studies of acupuncture for sudden-onset ankle sprains in adults are needed.
We identified only one randomised controlled trial (RCT), which compared plasma exchange with sham exchange, in 18 participants with either IgA or IgG paraproteinaemic neuropathy. The results were reported after three weeks of treatment. The trial did not report our primary outcome measure, which was improvement in disability measured by a validated scale six months after randomisation, or our other specified outcomes at six months. The trial demonstrated a modest benefit in improvement of weakness and overall disability as measured by the neuropathy disability score (NDS) over a period of three weeks. There was no improvement in this timescale in measures of sensory disturbance or electrical studies of the nerves. Adverse events were not reported. Further RCTs of this and other treatments with larger numbers of participants are needed. This is an update of a review first published in 2007. We found no additional trials for inclusion. The evidence is current to January 2014.
There was no statistically significant difference in the number of people who died during treatment with formoterol compared with placebo or salbutamol. Because so few people die of asthma, huge trials or observational studies are normally required to detect a difference in death rates from asthma. There were more non-fatal serious adverse events in people taking formoterol compared to those on placebo; for every 149 people treated with formoterol for 16 weeks, one extra non-fatal event occurred in comparison with placebo. There was no significant difference in serious adverse events in people on formoterol compared to regular salbutamol. We conclude that regular formoterol should not be taken by people who are not taking regular inhaled steroids due to the increased risk of serious adverse events. Formoterol should not be used as a substitute for inhaled corticosteroids, and adherence with inhaled steroids should be kept under review if separate inhalers are used when formoterol is added to inhaled corticosteroids.
An update search was carried out in 2012 and the review now includes 55 studies that assess the effects of chlorpromazine in treating schizophrenia compared with no active treatment (‘dummy’ treatment or placebo). Evidence was, in the main, rated by the review authors as low quality. There is some evidence to suggest that chlorpromazine reduces relapse and improves people’s mental health, symptoms and functioning. However, the side effects of chlorpromazine are severe and debilitating. Chlorpromazine causes sleepiness and sedation. It also causes movement disorders (such as tremors and uncontrollable shaking), considerable weight gain and lowering of blood pressure with accompanying dizziness. Chlorpromazine is low-cost and widely available. Despite its many side effects, chlorpromazine is likely to remain a benchmark drug and one of the most widely used treatments for schizophrenia worldwide. It should be noted that the quality of evidence from the 55 included studies was low and in addition to this, 315 studies were excluded because of flaws in the reporting of information or data and in research design and methods. Larger, better conducted and reported trials should focus on important outcomes such as quality of life, levels of satisfaction, relapse, hospital discharge or admission and number of violent incidents.
This review included 11 trials of cognitive training and a single trial of cognitive rehabilitation. We found no evidence for the efficacy of cognitive training in improving cognitive functioning, mood or activities of daily living in people with mild to moderate Alzheimer's disease or vascular dementia; however the quality of the studies was generally not high. The single trial of cognitive rehabilitation provided preliminary indications of the potential benefits of individual cognitive rehabilitation in improving activities of daily living in people with mild Alzheimer's disease. More high-quality trials of both cognitive training and cognitive rehabilitation are needed to establish their efficacy for people with early-stage dementia.
The evidence is current to August 2016. We could only identify one trial, which was terminated early due to recruitment problems. This study enrolled only 24 participants of the required 150. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. There was no difference between the two drugs in their ability to control seizure activity. The only difference noted was the requirement for prolonged mechanical ventilation for patients in the thiopental sodium group. This could be due to the prolonged presence of the drug in the body due to its slow removal. We judged the quality of the evidence for our primary outcomes of total control of seizures and in-hospital mortality to be low. There is a clear need for a large randomised controlled trial to study the efficacy of anaesthetic agents in the treatment of RSE.
We included four studies, with 823 participants in total, comparing exercise for increased-risk individuals against control or no treatment. Follow-up of patients ranged from 16 weeks to six months. No study assessed cardiovascular or all-cause mortality, or cardiovascular events as individual outcomes. One or more of the studies reported on total cardiovascular risk, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, blood pressure, body mass index, exercise capacity, and health-related quality of life, but the results did not provide conclusive evidence of the effects of exercise in this population. The included studies did not assess smoking cessation or any adverse effects of the exercise intervention. We conclude that the evidence to date is entirely limited to small studies in terms of sample size, short-term follow-up, and high-risk of methodological bias, which makes it difficult to derive any conclusions on the efficacy or safety of the exercise carried out in the included trials on total cardiovascular risk, mortality, or cardiovascular events. It is necessary to conduct high-quality clinical trials that evaluate the effect of exercise on people with increased cardiovascular risk.
Our systematic review found 19 studies involving 2256 children that use epinephrine for the treatment of bronchiolitis in acute care settings. When comparing epinephrine with placebo, no differences were found for length of hospital stay but there is some indication that epinephrine is effective for reducing hospital admissions. Exploratory results from one large, high-quality trial suggest that combined treatment with systemic glucocorticoids (dexamethasone) and epinephrine may significantly reduce admissions. There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among children admitted to the hospital. The evidence shows no important differences in adverse effects with epinephrine over the short-term with long-term safety not being assessed. Some limitations of this review include the quality of the included studies and inconsistent timing of measurement across studies which limited the number of children included in some meta-analyses. Further research is needed to confirm the efficacy, applicability and long-term safety of epinephrine as a treatment for bronchiolitis. In summary, our systematic review provides evidence that epinephrine is more effective than placebo for bronchiolitis in outpatients. Recent research suggests combined epinephrine and steroids may be effective for outpatients. There is no evidence to support the use of epinephrine for inpatients.
This review identified seven trials, with over 10,000 patients, that tested skin antiseptics (chlorhexidine solution) against normal soap or no presurgical washing. The review of these trials did not show clear evidence that the use of chlorhexidine solution before surgery was better than other wash products at preventing surgical site infections from developing after surgery.
We included eight trials with a total of 391 participants. Six trials focused on children and two on adults. The trials compared chest tube drainage (non-surgical), with or without fibrinolysis, to either VATS or thoracotomy (surgical). Two studies declared no financial conflicts of interest; the remaining six studies did not report funding source. There was no difference in the proportion of patients of all ages who survived empyema in relation to surgical or non-surgical treatment. However, this finding was based on limited data: one study reported one death with each treatment option, and seven studies reported no deaths. There was no difference in rates of complications between patients treated with surgical or non-surgical options. There was limited evidence to suggest that VATS reduced length of stay in hospital compared to non-surgical treatments. The quality of the evidence was moderate overall. The main limitations were few included studies for each analysis and inconsistencies among studies.
One study that tested the effectiveness of tacrolimus as therapy for treatment resistant ulcerative colitis was reviewed. Ulcerative colitis is a relapsing inflammatory disease restricted to the colon. Symptoms include bloody diarrhea, passage of pus and/or mucus and abdominal cramping during bowel movements. Tacrolimus is an immunosuppressant that may inhibit transcription of the interleukin 2 gene required for T cell activation thereby suppressing the inflammation associated with ulcerative colitis. The study compared two dosing regimens of tacrolimus (high serum concentration and low serum concentration) with placebo (inactive pill) and found that tacrolimus was effective for improving the symptoms of ulcerative colitis at two weeks. No benefit for induction of remission was noted. Patients in the high serum concentration group were significantly more likely than placebo patients to experience side effects related to treatment. Most of the side effects that occurred during the study were mild and included finger tremor, sleepiness, hot flush, headache, queasiness, stomach discomfort, hypomagnesemia and kidney problems. Two patients developed serious side effects during the study. One patient in the high serum concentration group developed serious viral gastroenteritis. A patient in the low serum concentration group developed Acinetobacter sepsis. Tacrolimus treatment was withdrawn in these patients and both patients recovered after medical therapy. Other side effects that have been associated with tacrolimus in other studies included liver problems, seizures, hypertension, diabetes mellitus, hyperkalemia, itching, insomnia, confusion, loss of appetite, hyperglycemia, weakness, depression, cramps, neuropathy, and infections. Tacrolimus may be effective for short-term improvement in symptoms in patients with treatment resistant colitis. There are no data from controlled trials to allow conclusions with regard to long term safety and effectiveness. The use of tacrolimus needs to be weighed against the potential risk of serious side effects. More data from well designed and controlled studies are needed to determine the long-term safety and effectiveness of tacrolimus.
We included 85 studies involving 9765 participants, of which 75 trials compared laparoscopic appendectomy versus open appendectomy in adults. The remaining 10 studies included only children. The evidence is current to February 2018. The main advantages of laparoscopic compared to open appendectomy were reduced postsurgical pain, reduced risk of wound infection, shorter hospital stay, and more rapid return to normal activities in adults. In contrast, laparoscopic appendectomy showed advantages over open appendectomy in wound infections and shorter hospital stay in children. Two studies reported that adults who received laparoscopic appendectomy had better quality of life two weeks, six weeks, and six months after surgery. Data from children were not available. As for disadvantages of laparoscopic appendectomy, a higher rate of intra-abdominal abscesses were identified in adults but not in children. Except for a trend towards decreased intra-abdominal abscesses after LA, the results for children were similar to those seen in adults. The quality of the evidence varied from moderate to low because of poorly conducted studies.
This review aimed to assess whether increasing fluid intake of breastfeeding mothers has a beneficial effect on breast milk production and infant growth. However, the review only identified one small quasi-randomised controlled trial (involving 210 women). The trial was of low quality and did not report on two of this review's important outcomes (satisfactory weight gain in the infant or duration of exclusive breastfeeding). The study did report on breast milk production (this review's other main outcome), but the data were not in a format that would permit further analysis in this review. The trial reported that advising women to consume extra fluids did not result in increased breast milk production, as measured by test feeds (also known as test weighing). In the 1950s, when the study was conducted, it was common for babies in developed countries to be weighed before and after a feed, known as test weighing or test feeding. However, this practice is not now routinely practiced for term infants due to concerns about lack of precision as a measure of breast milk production. The included study did not report any of this review's secondary outcomes: duration of any breastfeeding; mother's satisfaction with breastfeeding; hydration in mother; dehydration in the infant; or episodes of gastrointestinal illness. The effect of additional fluids for breastfeeding mothers remains unknown, due to a lack of well-conducted trials. However, because the physiological basis for any such improvement remains unclear, the conduct of further clinical trials may not be a priority. There is not enough evidence to support an increased fluid intake beyond what breastfeeding mothers are likely to require to meet their physiological needs.
This review is based on 27 studies including 1251 participants. Participants were children and adolescents aged under 16 years who had prominent upper front teeth (Class II Division 1 malocclusion). The evidence in this review is up to date as of 27 September 2017. The evidence suggests that providing orthodontic early treatment to children with prominent upper front teeth reduces the incidence of damage to upper incisor teeth significantly (middle four teeth at the top) as compared to treatment that is provided in one phase in adolescence. There are no other advantages of providing a two-phase treatment (i.e. between age seven to 11 years and again in adolescence) compared to treatment in one phase in adolescence. The evidence also suggests that providing treatment with functional appliances for adolescents with prominent upper front teeth, significantly reduces their prominence when compared to adolescents who did not receive any treatment. The studies did not suggest that any particular appliance was better than any other for reducing teeth prominence. The overall quality of the evidence is low for most comparisons and outcomes, therefore further research is needed and may change the findings.
We searched for evidence (January 2017) and included two trials involving 4523 women and their babies. Both trials were conducted in Ireland and were at a moderate to high risk of bias. We could not combine the data from these trials because they looked at different interventions and comparisons. One compared ‘universal’ screening with ‘risk factor’-based screening for GDM. The other compared screening women at their general practitioners' clinic (primary care) versus at the hospital (secondary care). In one trial (with information available for 3152 women), more women were diagnosed with GDM in the group of women who received ‘universal’ screening, compared with the group of women with ‘risk factor’-based screening (low-quality evidence). The trial did not report on outcomes relating to the mothers, including high blood pressure disorders of pregnancy, caesarean birth, perineal trauma, weight gain in pregnancy, postnatal depression, and type 2 diabetes. The trial did not report outcomes relating to the babies including being born large-for-gestational age, death (before or shortly after birth), death or a serious complication, hypoglycaemia, or adiposity, type 2 diabetes, and disability in childhood or adulthood. In the second trial (with information available for 690 women), screening at the general practitioner's clinic versus the hospital did not make a clear difference to the number of women diagnosed with GDM (low-quality evidence), high blood pressure (low-quality evidence), pre-eclampsia (low-quality evidence), or the number who had a caesarean birth (low-quality evidence). This trial did not report perineal trauma, weight gain in pregnancy, postnatal depression, or type 2 diabetes. Screening at the general practitioner's clinic versus at the hospital did not make a clear difference to the number of babies born large-for-gestational age (low-quality evidence), death (before or shortly after birth), death or a serious complication (low-quality evidence), or hypoglycaemia (very low-quality evidence). Childhood or adulthood adiposity, type 2 diabetes, and disability were not reported in the trial. There is not enough evidence to guide us on effects of screening for GDM based on different risk profiles or settings on outcomes for women and their babies. Further large, well-designed, randomised controlled trials are required to assess important short- and long-term outcomes for mothers and their babies.
In this review we included seven small trials, involving a total of 153 participants, that examined psychotherapeutic treatments for depression in older people. Five trials compared a form of cognitive behavioural therapy (CBT) against control conditions, and the findings showed that CBT was more effective than control. Two individual trials compared CBT against psychodynamic therapy, with no significant difference in effectiveness indicated between the two approaches. Our review shows that there is relatively little research in this field and care must be taken in generalising what evidence there is to clinical populations.
Cochrane Oral Health carried out this review of existing studies, which includes evidence current up to 8 March 2013. This review includes 13 published studies in which a total of 417 children and adults randomly received different tooth preparations before fixed orthodontic braces were bonded to their teeth. Eleven of these studies compared SEPs with conventional etching, and two compared two different SEPs. Only five of the studies provided usable evidence for this review and the combined results did not enable a conclusion to be made about whether or not there is a difference in bond failure (when the orthodontic fixings come away from the tooth) between SEPs and conventional etching. There was also no usable evidence to suggest whether SEPs or conventional etchants lead to less decay around the etching site, or are associated with fewer costs or better participant satisfaction. There was also no usable evidence to enable conclusions to be drawn about which was the best SEP, acid, concentration or etching time. The evidence presented is of low quality due to issues with the way in which some of the studies were conducted.
The review included six studies on 206 people with pulmonary hypertension and we could combine data from five of these studies. We could only use data for 165 participants, however not all of these data could be included in the analysis for all outcome measures. The majority of studies implemented an inpatient exercise rehabilitation programme with only a small number of studies examining an outpatient programme. The methods used to conduct these trials were of low quality. Given this low-quality evidence, it was not possible to generalise the results of this review across the spectrum of people with pulmonary hypertension.
Several studies have been carried out to determine the efficacy and safety of this intervention, but most had important methodological limitations and high risk of performance bias in relation to subjective outcomes such as angina pain. Overall, 43.8% of patients in the group treated with laser had their chest pain improved significantly, compared with 14.8% in the medication group. However, the evaluation of chest pain was performed without blinding (patients and doctors were aware of the intervention) and this may have biased the results. On the other hand, the risk of dying at one year was similar between the groups, but there is an excess risk of early mortality following the intervention in the laser group. This updated review concludes that there is no evidence of clinical benefits after TMLR, but data on safety suggests that the procedure may pose unacceptable risks. The intervention is becoming obsolete and it is not expected that new research in this field would change this conclusion.
We rated the quality of the evidence from studies using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. Overall, the quality of the evidence was low for the effect on thigh muscle strength and very low to moderate for the effects on other outcomes. There were problems with the design of some studies; often people taking part or assessors knew if they were receiving or testing NMES. In addition, the results for many outcomes were inconsistent or imprecise. This review suggests that NMES is a potentially effective treatment for muscle weakness in people with progressive diseases such as cancer, advanced chronic respiratory disease, and chronic heart failure, though the quality of the evidence is low. NMES might be considered for use within rehabilitation programmes. It was not possible to compare the effects of NMES to other forms of exercise, for example weight training, because the majority of studies compared NMES to a control group that received no treatment or a sham treatment. Further research is needed to understand the effect of NMES on the ability to exercise and quality of life.
We included a single trial with 39 participants in the review (20 in the yoga group and 19 in the control group). The trial looked at a seven-week Tibetan Yoga program in a group of people with Hodgkin and non-Hodgkin's lymphoma. The average age was 51 years. The trial involved patients who were currently receiving anti-cancer therapy as well as patients who were not receiving active therapy. The trial found insufficient data to make a judgement about the efficacy of yoga on distress, fatigue, depression and anxiety compared with patients not practicing yoga. Yoga can improve the patients' quality of sleep. The trial gave no information about health-related quality of life, overall survival or adverse events. On the basis of the GRADE criteria, we judged the overall quality of evidence for yoga concerning the outcomes distress, fatigue, anxiety, depression and quality of sleep as 'very low'. There are not enough data to say how effective yoga is in the management of haematological malignancies. Therefore, the role of yoga for haematological malignancies remains unclear. Further large, high-quality randomised controlled trials are needed. The evidence is up-to-date as of 4 February 2014.
This review includes a total of seven studies, involving 582 women and examines which techniques are safest for mother and baby. The risk of bias in trials was variable, with some trials not adequately describing the methods of randomisation. At an emergency caesarean after a long labour, there is evidence from the developing world that delivery of the buttocks or feet of the baby first (reverse breech extraction) is safer than delivery of the head by pushing from the vagina back into the uterus. In four trials involving 357 women, delivery of the buttocks or feet first was associated with fewer adverse outcomes for the mother, including less bleeding, infection and a shorter operation duration. There was no significant difference in trauma to the baby but admission to special care or neonatal intensive care was decreased with delivery of the buttocks or feet first than when the head was pushed up from the vagina. At a planned, non-labouring caesarean section there is limited evidence to support techniques (forceps or vacuum extractor on the baby's head) other than the use of the surgeon's hands to deliver the head of the baby through the uterine incision. Two trials involving 128 women compared forceps/vacuum with manual delivery without any significance difference in outcomes. There is also insufficient evidence to support the use of medication to relax the uterus (tocolysis) at the time of a caesarean to assist with safe delivery of the baby, with only one trial involving 97 women addressing this question.
This review of 13 trials on diabetic and alcoholic peripheral neuropathy with a total of 741 participants showed only one study that suggested possible short-term benefit from eight-week treatment with benfotiamine (a derivative of vitamin B1) with slightly greater improvement in vibration perception threshold compared to placebo. Vitamin B complex when given in a higher dose administered for four weeks was more efficacious than a lower dose in reducing pain and other clinical problems based on another study. Two to eight weeks of treatment with vitamin B was less efficacious than alpha-lipoic acid, cilostazol or cytidine triphosphate in short-term improvement of clinical and nerve test findings. All these findings require confirmation in larger studies before they can be accepted as definite. Vitamin B is generally well-tolerated with only a few reports of mild side effects.
We found one study comparing pregabalin versus placebo, involving 22 randomised participants with essential tremor. The impact of pregabalin on functional abilities and adverse effects is uncertain because the quality of the evidence is very low. The lack of studies and the significant limitations in the one included trial preclude firm conclusions about the risk-benefit profile of this treatment.
The use of Chinese herbs in a Western medicine context, without incorporating TCM methodology, has been evaluated in six trials, although again these are limited by their sample size and study length. The results of these six trials suggest that using Chinese herbs alone for psychotic symptoms may not be indicated, but if used in conjunction with Western antipsychotic drugs, they may be beneficial in terms of mental state, global functioning and decrease of adverse effects. However, further trials are needed before the effects of TCM for people with schizophrenia can be evaluated with any real confidence.
Several systematic reviews compared recombinant FSH with urinary gonadotrophins (HMG, purified FSH, highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. We included 42 trials with in total 9606 couples. Comparing rFSH with urinary gonadotrophins overall did not result in any difference in live birth rate, OHSS or any of the other outcomes. Comparing rFSH with HMG/HP-HMG resulted in a significantly lower live birth rate in the rFSH group though differences were small. There was no proof of a difference in live birth when comparing rFSH with FSH-P or with FSH-HP. We may conclude that all these gonadotrophins are equally effective and safe, and that further trials are unwarranted.
There were seven randomised controlled trials to include in this review. Each trial compared different interventions in generalised MG: (1) azathioprine plus initial prednisolone versus prednisolone - 41 participants; (2) azathioprine plus prednisolone versus prednisolone plus placebo (dummy treatment) - 34 participants; (3) ciclosporin monotherapy versus placebo - 20 participants; (4) ciclosporin plus prednisolone versus prednisolone plus placebo - 39 participants; (5) cyclophosphamide plus prednisolone versus prednisolone plus placebo - 23 participants; (6) mycophenolate mofetil plus either ciclosporin or prednisolone or no immunosuppressants versus placebo plus either ciclosporin or prednisolone or no immunosuppressants trial - 14 participants; (7) tacrolimus plus corticosteroids with or without plasma exchange versus no tacrolimus plus corticosteroids with or without plasma exchange trial - 34 participants. It is difficult to draw useful clinical conclusions from this small number of often short-term, randomised controlled trials. Each trial had relatively few participants and different trials used different study designs. The limited evidence available found that MG improved significantly with either ciclosporin (alone or in combination with corticosteroids) or cyclophosphamide (in combination with corticosteroids) compared with placebo. There is no clear evidence from randomised controlled trials of benefit for any of the immunosuppressant drugs used more commonly in MG - azathioprine (alone or in combination with corticosteroids), mycophenolate mofetil (as monotherapy or in combination with either corticosteroids or ciclosporin) or tacrolimus (in combination with corticosteroids or plasma exchange or both). There is no randomised controlled trial of methotrexate in MG. Long-term studies of the potentially formidable toxic effects of all of these drugs are lacking in MG.
We found five main studies with suitable methods for examining the effect of slum upgrading on health, quality of life and social wellbeing (for example poverty). Nine supporting studies were also included, which used methods that could indicate associations between interventions and outcomes but could not assess whether interventions caused the effect. Only one main study had a low risk of bias, with the rest having a mixed or high risk of bias. The majority of supporting studies had a high risk of bias, meaning their methods had several limitations that made the study results unreliable. In addition, the studies measured different interventions and outcomes, making it difficult to compare results. Overall, there was limited but consistent evidence to suggest that slum upgrading may reduce diarrhoea in slum dwellers and their water-related expenses. There were mixed results for whether slum upgrading reduced parasitic infections, general measures of communicable diseases, financial poverty and unemployment outcomes. There was very little information on other health or social outcomes, or which types of interventions were most beneficial. Some of the studies asked slum dwellers for their views and their experiences of slum upgrading interventions. They suggested a number of reasons why facilities were not used as intended and which may have reduced the benefits. Future research, with improved study designs and common outcome measures, is needed to determine how best to improve the conditions of existing slums and to offer the most benefit to the health, quality of life and social wellbeing of slum dwellers.
Six randomised trials were included in this review, which found that short (three hour) infusions are more convenient and caused significantly fewer adverse (side) effects (i.e. decreased white blood cell counts, fever, infection or sore mouth). With short-infusion paclitaxel there is no obvious loss of effectiveness when compared with longer infusions, although further clinical trials are needed to be sure of this.
One study (22 adult participants) was included in the review. The participants with sickle cell disease had proteinuria or microalbuminuria and were selected randomly to be treated for six months with either captopril (an angiotensin-converting enzyme inhibitor) or placebo (dummy drug with no active medication). The results from this small study were not convincing, with minor analysis changes leading to very different study conclusions. This study did not show that angiotensin-converting enzyme (ACE) inhibitors could reduce the level of protein or albumin in the urine. The level of creatinine and potassium in the blood were reported constant throughout the study. No serious adverse events were noted, although the potential for causing low blood pressure should be highlighted. More long-term studies involving multiple centers and larger numbers of participants are needed. Overall, the study appeared to be well run, although the actual method used to assign participants to treatment groups was not reported, nor whether it was concealed which group they were assigned to.
We included 15 trials with 1376 participants. Two trials included more than two study groups comparing different EN formulations. Six trials compared immunonutrition (EN supplemented with substances potentially able to change the immune response) versus control (other EN, sham treatment (placebo) or no treatment), and six trials investigated EN enriched with probiotics (live bacteria or yeasts that replace or add to helpful bacteria in the gastrointestinal tract). Two trials researched the use of semi-elemental formulations, which are types of EN in which nutrients are broken down to smaller particles. Two trials studied fibre-enriched EN, which may stimulate the growth of intestinal micro-organisms. Only one trial compared immunonutrition enriched with probiotics and fibres versus control. Immunonutrition compared with control showed reduction in all-cause mortality. However, when only specific types of EN were compared, this could not be confirmed. Available evidence does not support the effectiveness of probiotics in AP. One trial that made this comparison reported a higher rate of serious adverse events, and consequently more occurrences of organ failure and higher mortality rate. When this trial was excluded, results showed a decrease in mortality, organ dysfunction and pancreatic infectious complications, but with evidence of low to very low quality. Fibre-enriched formulations had a beneficial effect on decreasing local non-infectious complications and shortening hospitalisation. No effects were confirmed for semi-elemental formulations and immunonutrition enriched with probiotics and fibres. These results are inconclusive because of the paucity of data. Comparison of any kind of EN versus no intervention revealed a beneficial effect on all-cause mortality. Overall, EN was associated with a rather small number of mild adverse events (most often nausea, vomiting, bloating, diarrhoea, pain relapse and higher serological concentrations of sodium) not requiring cessation of tube feeding. We cannot be certain that EN is safe in this population because the quality of evidence for adverse event outcomes is low. All included trials have been assessed as having high risk of bias, most often because they did not provide enough information for adequate assessment of certain study design characteristics, but also because some clear flaws were noted in the way they were designed and carried out. The quality of the evidence throughout this review is considered to be low to very low primarily because of the relatively small numbers of study participants and events included. Study results may reflect systematic and random errors.
We included seven trials involving 800 women. None of the included studies reported any maternal mortality. We did not combine the results of the trials because the trials were very different in the clinical interventions used and how the outcomes were assessed. One study reported higher maternal satisfaction with the use of general anaesthesia than sedation and analgesia. Paracervical block did not improve the control of postoperative pain when compared against sedation and analgesia. More nausea and vomiting were reported when opioid drugs were used. Currently, the levels of postoperative pain experienced by women undergoing surgical evacuation of incomplete miscarriage are not completely relieved. Further studies in this context should be conducted to address this question. Key factors that influence the choice of anaesthesia include availability, effectiveness, safety, side effects, and costs. Other factors include patient preference, practitioner choice, facility resources and medical indications.
We included 55 randomised trials on 3121 people with asthma. There are both chemical (10 trials) and physical methods such as mattress encasings (37 trials) of reducing mite allergen levels and we included both types in this review. There were also eight trials that used both physical and chemical methods. Many trials were of poor quality and would therefore be expected to exaggerate the reported effect, but we did not find an effect of the interventions. There was no difference in peak flow (a measure of lung function), asthma symptoms and medication scores, or the number of patients reporting an improvement in their asthma symptoms. While reducing exposure to house dust mites is recommended in guidelines, we did not find an effect of control measures to reduce the exposure to mites or their products. .
We conducted a search of the literature on 15 April 2016. We identified seven randomised controlled trials conducted in China, Japan, South Korea, Spain, Thailand, and the United States including a total of 577 participants. These trials compared the PGW technique versus persistent use of traditional techniques or other advanced techniques in people undergoing ERCP in whom access to the bile duct using traditional techniques was considered by the endoscopists to be difficult. As in clinical practice, the criteria used to define difficult access to the bile duct were highly variable among studies. We assessed outcomes of post-ERCP pancreatitis (PEP), success rates in accessing the bile duct, and other post-ERCP complications (bleeding, infection, hole in the bowel wall, death). Contrary to popular belief, the PGW technique appears to increase the risk of PEP and does not improve the success rate of gaining access to the bile duct compared to other endoscopic techniques. The technique may increase the risk of mild PEP, but not moderate or severe PEP. There was no significant difference in success rates for accessing the bile duct. The risks for other complications such as bleeding, hole in the bowel wall, inflammation of the bile duct, and death appear to be low. Overall, we considered the quality of evidence for the outcome of PEP to be low. We considered none of the included studies to be at low risk of bias for all criteria. In most of the studies, both the participants and the medical staff were aware of which method was being used, therefore their judgments may not have been objective and the results should be interpreted cautiously.
randomised clinical trials (studies where people are randomly put into one of two or more treatment groups) where participants had come to medical attention because they had taken a paracetamol overdose, intentionally or by accident, regardless of the amount of paracetamol taken or the age, sex, or other medical conditions of the person involved. There are many different interventions that can be used to try to treat people with paracetamol poisoning. These interventions include decreasing the absorption of the paracetamol ingested and hence decreasing the amount absorbed into the bloodstream. The agents include activated charcoal (that binds paracetamol together in the stomach), gastric lavage (stomach washout to remove as much paracetamol as possible), or ipecacuanha (a syrup that is swallowed and causes vomiting (being sick)). Paracetamol once absorbed into the bloodstream goes to the liver where the majority is broken down to harmless products. However, a small amount of the medicine is converted into a toxic product that the liver can normally handle but, when large amounts of paracetamol are taken, the liver is overwhelmed. As a consequence, the toxic product can damage the liver leading to liver failure, kidney failure, and in some cases death. Other interventions to treat paracetamol poisoning include medicines (antidotes) that may decrease the amount of the toxic products (such as a medicine called cimetidine) or breakdown the toxic products (including medicines called methionine, cysteamine, dimercaprol, or acetylcysteine). Finally, attempts can be made to remove paracetamol and its toxic products from the bloodstream using special blood cleansing equipment. All these treatments were examined. We found 11 randomised clinical trials with 700 participants. Most of these trials looked at different treatments. activated charcoal, gastric lavage, and ipecacuanha may reduce absorption of paracetamol if started within one to two hours of paracetamol ingestion, but the clinical benefit was unclear. Activated charcoal seems to be the best choice if the person is able to take it. People may not be able to take charcoal if they are drowsy and some may dislike its taste or texture (or both). Of the treatments that remove the toxic products of paracetamol, acetylcysteine seems to reduce the rate of liver injury from paracetamol poisoning. Furthermore, it has fewer side effects than some other antidotes such as dimercaprol and cysteamine; its superiority to methionine was unclear. Acetylcysteine should be given to people with paracetamol poisoning at risk of liver damage, risk is determined by the dose ingested, time of ingestion, and investigations. More recent clinical trials have looked at ways to decrease side effects of intravenous (into a vein) acetylcysteine treatment, by altering the way it is given. These trials have shown that by using a slower infusion and lower initial dose of acetylcysteine, the proportion of side effects such as nausea (feeling sick) and vomiting, and allergy (the body's bad reaction to the medicine such as a rash) may be lowered. this review of interventions for paracetamol poisoning found surprisingly few published randomised clinical trials for this very common condition. Furthermore, the majority of trials had few participants and all were at high risk of bias. Accordingly, the quality of the evidence should be considered as low or very low.
This review of the evidence found one randomised controlled trial (RCT) of the LNG-IUS versus oral progestin therapy in women with any type of endometrial hyperplasia. It was conducted in Norway and included 153 women, but only 19 of the women had a confirmed histological diagnosis of atypical endometrial hyperplasia; the other women had other types of endometrial hyperplasia. The evidence is current to July 2018. The included RCT compared LNG-IUS versus oral continuous or cyclic medroxyprogesterone (MPA) for treating endometrial hyperplasia. After six months of treatment, there was insufficient evidence to determine whether there was a difference in regression rates between the LNG-IUS group and the MPA group. The rate of regression was 100% in the LNG-IUS group (n = 6/6) and 77% in the MPA group (n = 10/13). Among the total study population (N = 153), over the six months' treatment the main adverse effects were nausea and vaginal bleeding. There was no evidence of a difference between the groups in rates of nausea, but vaginal bleeding was more common in the LNG-IUS group. The quality of the evidence was low or very low for all outcomes. The included study was at low risk of bias, but the quality of the evidence was very seriously limited by imprecision and indirectness.
We identified 25 randomised clinical trials involving 2505 people undergoing laparoscopic cholecystectomy. Most participants in the trials were low anaesthetic risk people undergoing planned laparoscopic cholecystectomy. The choice of whether the participants received the different painkillers (or not) was determined by a method similar to the toss of coin so that the treatments compared were conducted in people who were as similar as possible. The treatments in all the included trials were aimed at decreasing the pain after laparoscopic cholecystectomy before the participants reported pain. Participants were allowed to take additional painkillers as required in most of the trials. There were no deaths in either group in three trials (183 participants) that reported deaths. The differences in the serious complications between the groups was imprecise in all the comparisons. None of the trials reported quality of life or the time taken to return to normal activity. The differences in length of hospital stay and the time taken to return to work was imprecise in all the comparisons that reported these. Pain was lower in the participants who received painkillers compared with those who received controls at 4 to 8 hours and at 9 to 24 hours as measured by the visual analogue scale (a chart that rates the amount of pain on a scale of 1 to 10). This is a modest reduction and is comparable to other methods of pain reduction such as administering local anaesthetics (drugs that numb part of the body, similar to the ones used by the dentist to prevent the people from feeling pain) during the operation. In summary, different painkillers reduce pain scores in low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. The overall quality of evidence was very low. Further trials are necessary. Such trials should include outcomes such as quality of life, the time taken to return to normal activity, and the time taken to return to work, which are important for the person undergoing laparoscopic cholecystectomy and the people who provide funds for the treatment.
The review identified four large randomised controlled trials (3925 women) that compared treatment with breast conserving surgery alone and breast conserving surgery with the addition of RT. The addition of RT reduced the risk of a recurrence of either DCIS or invasive cancer in the treated breast by 51%. Older trials of breast conserving surgery followed by RT for invasive breast cancer have shown long-term toxicity from the addition of RT. We found no evidence of increased toxicity from the use of RT although some trials did not report on the causes of non-breast cancer deaths (deaths which potentially could be related to side effects). The number of non-breast cancer deaths reported were similar in both radiotherapy and control groups. Changes in delivery of RT between older and more recent trials and a subsequent decrease in exposure of normal tissue may account for this finding. Longer follow up of trial participants is required before a definite conclusion can be drawn, however radiotherapy techniques are continuing to improve and future patients are likely to experience a further decrease in exposure of nearby normal tissues. Overall survival was high and similar between each group whether radiotherapy was used or not. There were no reports of short-term toxicity from use of radiotherapy, or quality of life data.
This review identified four randomised controlled trials including 149 adult patients with idiopathic acute vestibular dysfunction (vestibular neuritis) treated with either corticosteroids or placebo. The studies were varied in that they used different drugs and different treatment regimens. On the basis of these studies, there is currently insufficient evidence in favour of corticosteroids over placebo medication in the symptomatic recovery and objective testing of vestibular function, both in the short-term and long-term. Further studies of higher quality are needed to test the effectiveness of corticosteroids in patients with the condition.
We included a total of 10 studies recruiting 6292 apparently healthy adults in this review. The findings of the review indicate that interventions can successfully support adults' attempts to become active and fitter, for example with personal counselling and advice, feedback and offering choices of exercise, and supervision. Outcomes are improved if the intervention comprises a specified type of physical activity and is supervised by a non-health professional using a combination of group and individual approaches. New physical activity can be maintained for up to at least one year and does not increase the risk of falls or exercise related injuries. More research is needed to establish which methods of exercise promotion work best in the long term to encourage specific groups of people to be more physically active.
This review looks at the effectiveness of depot flupenthixol decanoate in comparison with no active treatment (placebo), oral antipsychotics and other depot preparations for people with schizophrenia and other severe mental illnesses. An electronic search for relevant trials was carried out in 2013. Fifteen trials with 626 participants could be included. All evidence from these trials was rated by the authors to be low or very low quality. Currently, from the data reported, there is nothing to choose between depot flupenthixol decanoate and other depot or oral antipsychotics. There was some evidence that it would be understandable to offer a standard dose rather than the high dose depot flupenthixol as there is no difference in relapse. Overall, this review highlights the lack of evidence based information available for the review question and the need for large, well-designed and reported randomised clinical trials to address the medical, social, personal and economic effects of flupenthixol decanoate. This plain language summary has been written by a consumer Ben Gray, Service User and Service User Expert: Rethink Mental Illness.
The authors of this review assessed the efficacy and safety of laquinimod in patients with MS. Concerning the outcomes, they considered relapse, disability progression, inflammatory lesion, and brain atrophy. Among the pertinent literature only one study met the inclusion criteria. The study involved a total of 1106 patients with relapsing-remitting MS and evaluated the efficacy and safety of laquinimod as unique therapy versus placebo. As far as safety was concerned, common adverse events included headache, back pain, arthralgia, diarrhoea, cough, urinary tract infection, elevated alanine aminotransferase, insomnia, nausea, abdominal pain and sinusitis. The authors were unable to give any clear recommendations for the use of laquinimod as a DMD for MS because the study was poor quality and was funded by a pharmaceutical company. Future studies with higher methodological quality are needed to assess the potential benefits and the safety in a longer period of administration.
The review found seven individual randomised controlled trials (RCTs), two cluster-RCTs and four quasi-RCTs involving 8,698 participants examining a variety of behavioral interventions to evaluate whether they reduced HIV/STIs rates or resulted in changed behavior among sex workers and their clients. Results showed that the interventions were effective in HIV/STI prevention, including reducing the incidence and prevalence of HIV and STIs. Furthermore, there were some differences in self-reported behavior including increased condom use and a reduction in the risk of drug use. However, these trials were small and generally had few participants. As a result, evidence for the effectiveness of social cognitive theory and promoting condom use in reducing HIV/STI incidence compared to other behavioral interventions was limited, because no RCTs examined the effects of these interventions on HIV prevalence or on sex workers other than FSWs. In future research and program agendas therefore it is important to assess other potentially more potent behavioral change strategies.
The evidence is current to June 2017. Ten trials met our inclusion criteria, and included 1815 people. Three trials compared phenytoin (an AED) with a placebo or no treatment. One trial compared the AEDs phenytoin or carbamazepine with no treatment. One trial compared the AEDs phenytoin or phenobarbital with no treatment. Five other trials were head-to-head trials (where one drug is directly compared against another drug) of AEDs (phenytoin versus valproate; zonisamide versus phenobarbital and levetiracetam versus phenytoin). We did not find any consistent evidence to suggest that preventative AED treatments are effective in reducing the number of seizures that occurred postsurgery, deaths or adverse effects. Taking all the trials together, we considered that the quality of the evidence was low due to potential problems with the designs of the trials. Also the differences in the designs of the trials relating to the treatments examined and the results reported meant that it was difficult to compare results across trials. Further good-quality studies are needed to validate the findings mentioned above.
Vitamin C was identified in the early 1900s and suggestions that one of its biological roles may be to resist infections are supported by numerous animal studies. We looked for studies in humans and found three trials with a total of 2335 participants that looked at whether vitamin C prevents pneumonia in the community. Two of these preventive trials studied soldiers while the third studied boys in a UK boarding school in the 1940s. Two therapeutic trials with a total of 197 pneumonia patients looked at whether vitamin C might be beneficial for pneumonia patients. One studied patients aged 66 to 94 years in the UK with pneumonia. The other therapeutic trial was conducted in the former Soviet Union but the social and nutritional backgrounds of the patients were not described. One study with 37 burns patients examined the effect of vitamin C on hospital-acquired pneumonia. Our searches were up-date-as of April 2013. Five of the identified trials found preventive or therapeutic benefits of vitamin C against pneumonia but the study on hospital-acquired pneumonia found no effect. The overall quality of the studies was good. However, the five trials with positive findings were carried out in such extraordinary conditions that the results should not be extrapolated to the general population. Therefore, more research is needed. In the meantime, supplementing pneumonia patients who have low plasma vitamin C levels may be reasonable because of its safety and low cost. None of the five trials reported noteworthy adverse effects of vitamin C.
This review was designed to help find out if research studies could tell us which kind of placement is best. We found 102 studies with 666,615 children that met the methodological standards we considered acceptable. Wherever possible we combined the data from studies looking at the same outcome for children, in order to be more confident about what the research was telling us. Current best evidence suggests that children in kinship foster care may do better than children in traditional foster care in terms of their behavioural development, mental health functioning, and placement stability. Children in traditional foster care placements may do better with regard to achieving adoption and accessing services they may need. There were no negative effects experienced by children who were placed in kinship care. The major limitation of this systematic review is that the quality of research on kinship care is weakened by the poor methods of the included studies. Implications for practice and future research are discussed.
Five RCTs involving 604 people were included in this review. Analyses of these studies showed that the incidence of moderate forms of GvHD can be reduced by prophylactic corticosteroid regimens. However, there is no evidence that the incidence of life-threatening forms or patient mortality can be reduced. Effects on quality of life could not be estimated because this information was not systematically collected during these studies. Further studies are needed to determine if the timing of steroid administration influences the outcomes of GvHD.
Colchicine, a plant alkaloid, has been used to treat patients with primary biliary cirrhosis and was tested in randomised clinical trials. When all identified trials were combined, colchicine appeared to be not significantly different from placebo/no intervention in respect to mortality, mortality and/or patients who underwent liver transplantation, liver complications, liver biochemistry, liver histology, and the occurrences of adverse events. Colchicine may reduce pruritus, but this finding may be due to bias. The addition of ursodeoxycholic acid did not significantly influence the effect of colchicine.
We included all randomized trials and quasi-randomized trials comparing the frequency of TNS and neurological complications after spinal anaesthesia with lidocaine compared to other local anaesthetic agents. Randomized trials compare two or more treatments where the treatments are allocated to participants in a random manner that cannot be predicted by the study organizers. Quasi-randomized studies are similar but are not truly random, but carry a greater likelihood that the study organizer can predict which treatment the participants receive (e.g. based on date of birth or the order in which people were recruited). The evidence is current to 25 November 2018. We included 24 trials reporting on 2226 participants, 239 of whom developed TNS. There was no evidence TNS was associated with any specific neurological disease and symptoms disappeared spontaneously by the fifth postoperative day. The risk of developing TNS with lidocaine for spinal anaesthesia was increased compared to bupivacaine, prilocaine, or procaine; and similar compared to 2-chloroprocaine and mepivacaine. Specifically, when alternative local anaesthetics were compared directly to lidocaine, the risk of developing TNS was reduced by between 82% and 90% when bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine were used rather than lidocaine. There were no clear differences in TNS between lidocaine and 2-chloroprocaine or mepivacaine. In the case of 2-chloroprocaine, TNS occurred in only one study and the results varied greatly for the small number of participants. Painful symptoms stopped by the fifth postoperative day in all participants. Among pregnant women undergoing surgery, only 3/310 women developed TNS; no conclusions could be drawn on whether symptoms were more likely with lidocaine. The authors also used the statistical method of network meta-analysis to compare the various local anaesthetics. This analysis similarly showed that the risk of TNS was lower for bupivacaine, levobupivacaine, prilocaine, procaine, and ropivacaine, while 2-chloroprocaine and mepivacaine did not differ in risk of TNS compared to lidocaine. Due to the very low- to moderate-quality of evidence among currently available studies, future research efforts in this field are needed to assess alternatives to lidocaine that can provide high-quality anaesthesia without TNS development. Lidocaine has been the drug of choice for inducing spinal anaesthesia in ambulatory surgery (or day surgery) because of its rapid onset of action, intense nerve blockade, and short duration of action. The present review shows that lidocaine is more likely to cause TNS than bupivacaine, prilocaine, and procaine. However, these drugs produce longer local anaesthetic effects and therefore are not desirable for ambulatory patients. Our results suggest that 2-chloroprocaine might be a viable alternative to lidocaine for day surgery of short duration and obstetric procedures since this local anaesthetic has a rapid onset of action, is quickly metabolized, and has low toxicity. However, this conclusion is based on only two studies and low-quality evidence.
The evidence is up-to-date to January 2016. We included 30 trials involving 2319 participants. We looked at trials that compared midazolam with no active treatment ('dummy' treatment/placebo) or a different medication for sedation before a procedure. The trials involved children and adults having procedures to diagnose medical problems rather than procedures for treatment of a disease. We disregarded trials where people received a general anaesthetic or other medications for sedation or pain relief in addition to midazolam during their procedure. Midazolam administered into the bloodstream compared with other medications did not seem to make the participants more drowsy, reduce anxiety or pain, or make the procedure easier to perform. This is based on the low-quality evidence currently available. A potential benefit is that children and adults who received midazolam compared with no active treatment did not remember as much about the procedures. Midazolam made them drowsy, reduced anxiety and made it easier to perform a procedure. There is moderate-quality evidence that a solution of midazolam given to children to drink before a procedure was not as effective as a different medication called chloral hydrate. A nasal spray of midazolam before a procedure made the participants drowsy and reduced their anxiety, but this did not make it easier to perform procedures on them. This review cannot be used to assess the harms of midazolam for sedation before a procedure. We rated the evidence, in the main, as being of low quality. Particularly concerning was that many trials did not explain how participants were randomized to either midazolam or to a different treatment, and that the results did not give us a very clearly defined answer.
We included two studies with a total of 1711 participants in our review. Both studies involved adults without severe periodontitis who were regular attenders at dental appointments in the UK. The studies were conducted in general dental practices, which is the most appropriate setting to evaluate 'routine scale and polish' treatments. One study measured outcomes at 24 months and one study at 36 months. The studies found little or no difference between regular planned scale and polish treatments compared with no scheduled scale and polish for the early signs of gum disease (gingivitis or bleeding gums; plaque deposits; and probing depths or gum pockets). There was a small reduction in calculus (tartar) levels, but it was uncertain if this is important for patients or their dentists. Participants receiving six-monthly and 12-monthly scale and polish treatments reported feeling that their teeth were cleaner than those who were scheduled to receive no treatment. However, there did not seem to be a difference between groups in terms of quality of life. Available evidence on the costs of the treatments was uncertain. Neither of the studies measured side effects (such as damage to tooth surfaces and tooth sensitivity), changes in attachment level, tooth loss or halitosis (bad breath). Neither study compared scale and polish treatments provided by different professionals, e.g. dentists, dental therapists and hygienists. We judged the certainty of the evidence to be high for gingivitis, probing depths, calculus and quality of life, but low for plaque, and low to very low for patient perception of oral cleanliness. The certainty of evidence for costs was very low. The high-certainty evidence for gingivitis means that we can be confident that routine scale and polish does not significantly reduce the signs of mild gum disease when measured up to three years.
We identified five studies including 318 participants that reported the diagnostic test accuracy of ERCP and five studies including 654 participants that reported the diagnostic test accuracy of IOC. Most studies included people with symptoms (participants with jaundice or pancreatitis) who were suspected of having CBD stones based on blood tests, ultrasound (use of sound waves higher than audible range to differentiate tissues based on how they reflect the sound waves), or both, prior to the having ERCP or IOC. Most studies included participants who had not previously undergone cholecystectomy. Given an average sensitivity of 83% for ERCP, we would expect that on average 83 out of 100 people (this may vary between 72 and 90 out of 100 people) with CBD stones would be detected while the remaining 17 people would be missed and would not receive appropriate treatment. Based on an average specificity of 99% for ERCP, we would expect that on average 99 out of 100 people without CBD stones would be identified as not having CBD stones; 1 out of 100 (this could vary between 0 and 17 out of 100 people) would be false positive and would not receive appropriate treatment. For IOC, an average sensitivity of 99% means that on average 99 out of 100 people (this may vary between 83 and 100 out of 100 people) with CBD stones would be detected while only one person would be missed and would not receive appropriate treatment. In terms of specificity, an average of 99% for IOC means that 99 out of 100 people without CBD stones would be identified as not having CBD stones with only one false positive (this could vary between 0 and 5 out of 100 people) who would not receive appropriate treatment. It appears that both tests are fairly accurate in guiding further invasive treatment as most people diagnosed with CBD stones by these tests have CBD stones. However, some people may have CBD stones in spite of having a negative ERCP or IOC test result. Such people may have to be re-tested if the clinical suspicion of CBD stones is very high because of their symptoms. All the studies were of low methodological quality, which may question the validity of our findings. Further studies of high methodological quality are necessary.
We summarized medical literature regarding the effect of two to six days of oral antibiotics (short duration) in treating children with streptococcal throat infection, compared with 10 days of oral penicillin (standard duration). We included 20 studies with 13,102 cases of acute group A beta hemolytic streptococcus (GABHS) pharyngitis. The short duration treatment resulted in better compliance but more side effects. All side effects were self-limiting: mostly mild to moderate diarrhea, vomiting and abdominal pain. Three studies reported the rate of long duration complications with no statistically significant difference. Our study has several limitations. Firstly, only 3 out of the 20 included studies followed the participants for a sufficient duration to be able to study the prevalence of complications of GABHS pharyngitis. Although these three studies had a total of 8135 participants, results were too under-powered to draw any conclusions on differences in complication rates. This means our conclusion is not applicable in low-income countries where the prevalence of rheumatic heart disease is high. Another limitation is that the primary studies evaluated different antibiotics for variable durations (three to six days). Also, studies were of limited quality. Finally, although the shorter antibiotic duration appeared to be effective and more convenient, it is more expensive than the standard duration 10 days of penicillin. However, one must take into account the reality of patient behavior and the price of unsuccessful or incomplete therapy. Three to six days of oral antibiotics for children with streptococcal throat infection is a safe treatment with a comparable effect to the standard duration of 10 days of penicillin. However, our results must be interpreted with caution in low-income countries where acute rheumatic fever is still a problem.
Fourteen studies met our inclusion criteria for this review and none of the exclusion criteria. Aspirin, steroid and non-steroidal anti-inflammatory drugs (NSAIDs) (traditional and the selective cyclooxygenase-2 (COX-2) inhibitors) showed no significant benefit in the treatment of Alzheimer's disease. Therefore, the use of these drugs cannot be recommended for the treatment of Alzheimer's disease.
Two people looked for published and unpublished research in several databases and websites to find relevant studies comparing LAMA plus ICS with increased doses of ICS for asthma in adults. We analysed the results available up to April 2015 in this systematic review. What did we find? We found one study involving 210 patients with asthma. The trial compared adding tiotropium (a LAMA) to doubling the dose of beclomethasone (a steroid). In the trial, people taking a combination of the LAMA and ICS were slightly less likely to have an asthma attack needing treatment with oral steroids. Our results suggest that for every 1000 people, 18 fewer in the LAMA group would need these treatments compared to patients treated with an increased dose of ICS. However, there is a relatively wide margin of error in this estimate, and the actual number of patients on LAMA who might need steroids because of an asthma attack could range from 52 fewer to 26 more people per 1000. Similarly, neither option was more clearly beneficial on any of the following measures: asthma attacks resulting in hospitalisation or admission to the emergency department, serious adverse events, control of asthma or quality of life related to asthma. On the other hand, LAMA plus ICS might improve lung function a bit more than increasing ICS dose. We didn't have much confidence in the findings because the one included study only looked at one type of LAMA (tiotropium) for a short period of time (14 weeks).
We found two research studies that had assessed yoga for stroke survivors. Seventy-two people took part in the two studies. One study was in the USA and one was in Australia. On average, the stroke survivors were between 60 and 63 years old and it had been between four years three months and nine years since they had had a stroke. In the American study, yoga classes were held twice a week for eight weeks. In the Australian study, yoga classes were held once a week for 10 weeks. Both studies encouraged people to practice yoga at home, in their own time. Both studies used waiting-list control groups. This means that people in the control group could go to yoga classes at the end of the study. The American study was funded by the US Government. The Austrailian study was funded by the National Stroke Foundation (Australia). We were able to analyse study data from 69 participants. No significant benefit was found on measures of QoL, balance, strength, endurance, pain, disability scores. No significant benefit was found on measures of movement, although one study reported a significant benefit in improving aspects of range of movement. One study reported a significant benefit in reducing anxiety. Neither study reported on measures of patient harm. We assessed the quality of the evidence using GRADE. Overall, the quality of the evidence was very low, due to the small number of trials included in the review, both of which we judged to be at high risk of bias, particularly in relation to incompleteness of data and selective reporting, and especially regarding the representative nature of the sample in one study. The review could not identify enough high-quality evidence on the benefits and safety of yoga in stroke rehabilitation. More good-quality research studies are needed to be sure that yoga has benefits for stroke survivors.
Overall, we judged the quality of the evidence in this review for the main outcome of reduction in seizure frequency to be low due to unclear information in the published papers about how the studies were designed and unclear presentation of results. This review provides no information about the effect of TMS on quality of life. It is important that future studies are larger and measure important outcomes, such as the effect of TMS on reducing seizure frequency, improving quality of life, and any side-effects associated with TMS compared with other available treatments.
We included 55 studies. Thirty three of these studies helped us to gain a better understanding of the best way to deliver an asthma self-management intervention. Thirty three studies helped us to determine whether these interventions are successful in improving children's health and well-being. Eleven studies contributed to both. We included 23 studies in quantitative models measuring children's asthma outcomes (an outcome is something you can measure to find out if an intervention worked). Results show that school-based self-management interventions could improve outcomes such as hospitalisations, emergency department visits, and health-related quality of life. Fewer studies reported improved unplanned medical visits or reduced numbers of days on which children could not do their normal activities. Interventions did not reduce school absences, symptoms, or reliever medication use. The more effective interventions were based on theories about how the intervention might work. Researchers found that including parents in the intervention, making sure children were happy with the intervention, and running the intervention during school hours helped increase fidelity. Studies that measured whether an intervention worked were usually well designed; however sometimes they were difficult to carry out, and some may not have measured outcomes accurately. Reviewers found that some of the studies conducted to understand how an intervention should be delivered were at risk of bias, and certainty of the evidence was generally lower for these studies. Evidence suggests that school-based self-management interventions can help children with asthma and can reduce hospital admissions and trips to the emergency department. Study findings suggest that interventions that were based on a theory about how an intervention can be planned and delivered could prove useful in improving children's outcomes, reaching large numbers of children, and keeping dropout rates low, and indicate that those designing interventions should consider factors such as including parents. This review is current to August 2017.
In this analysis, we assessed the effect of CSFs on outcome after stroke using data from clinical trials of people with recent stroke. We included a total of 11 studies and 1275 participants. A higher death rate was observed in participants treated with erythropoietin (EPO) in three trials (782 participants); whether further trials of EPO will be performed early after stroke remains unclear. In eight small trials involving 548 participants, patterns of improvement after a stroke were observed using granulocyte colony stimulating factor (G-CSF) and further trials are ongoing. Currently, there is insufficient evidence to support the use of CSFs in the treatment of people with recent stroke.
We did not find any trials which have been completed on this topic with available results. The only trial which met our criteria for inclusion had been terminated due to encountering difficulties with recruiting participants. Therefore we cannot be sure whether controlling blood glucose intensively when people have diabetic foot ulcers is beneficial or harmful. The lack of evidence however should not deter efforts to achieve optimal glycaemic control in people with diabetic foot ulcers to encourage healing as is current practice. We believe there are currently two trials underway which may provide some evidence on this topic once completed. This Plain Language Summary is up to date as of 7 December 2015.
We included 35 randomised clinical trials with 3556 participants. One trial compared Radix Sophorae flavescentis with placebo; the remaining 34 trials compared effects of Radix Sophorae flavescentis in addition to a co-intervention versus the same co-intervention. The included trials assessed heterogenous forms and ways of administering Radix Sophorae flavescentis (e.g. oral capsules, oral tablets, intravenous infusion, intramuscular injection, acupoint (a specifically chosen site of acupuncture) injection) with treatment duration of 1 to 24 months. Two trials assessed children under 14 years of age. Participants in two trials had cirrhosis in chronic hepatitis B (late-stage scarring of the liver). Seven of the 35 randomised clinical trials received academic funding from government or hospital. Four trials received no funding. The remaining 24 trials provided no information on funding. Undisclosed funding may influence trial results and may lead to poor trial design. Only one of the 35 trials assessed mortality; no deaths occurred. Ten trials assessed serious adverse events; no serious adverse events occurred. None of the trials assessed health-related quality of life, and no trials followed people who died from hepatitis B or were at risk of dying because of hepatitis B. Adverse events considered 'not to be serious' was an outcome in 19 trials. We cannot say if Radix Sophorae flavescentis versus placebo or no intervention is better or worse regarding the occurrence of adverse events considered 'not to be serious'. Radix Sophorae flavescentis reduced the proportion of people with detectable HBV-DNA and also the proportion of people with detectable HBeAg. However, caution is needed to understand these beneficial findings, as these trials were at high risk of bias, and these outcomes have not yet been proven relevant to patients. The 432 trials identified could not be included in the review because of lack of information required for the conduct of this review. Accordingly, more information from properly designed randomised clinical trials is needed before one can determine the benefits or harms of Radix Sophorae flavescentis for people with chronic hepatitis B. 'Certainty of evidence' means "the extent of one's confidence that review results are correct in supporting or rejecting a finding". The certainty of evidence on the use of Radix Sophorae flavescentis for people with chronic HBV in terms of its beneficial or harmful effects on death, health-related quality of life, risk of dying due to HBV infection, and serious adverse events cannot be determined, as only a few trials aimed to explore patient-relevant outcomes. Our certainty in the evidence that Radix Sophorae flavescentis, when compared with no intervention or placebo, decreases or increases adverse events considered not to be serious in people with chronic hepatitis B is very low. Our certainty in the evidence that Radix Sophoae flavescentis decreases the proportion of people with detectable HBV-DNA and the proportion of people with detectable HBeAg is also very low. These assessments of certainty of evidence are due to the poor design and reporting of the included trials.
Our systematic review found 17 controlled studies involving 2596 affected children that used these drugs for a short duration and assessed short-term outcomes. When comparing glucocorticoids to placebo, no differences were found for either hospital admissions or length of hospital stay. There was no substantial benefit in other health outcomes. These findings are consistent and likely to be applicable in diverse settings. Exploratory results from one large high-quality trial suggest that combined treatment of systemic glucocorticoids (dexamethasone) and bronchodilators (epinephrine) may significantly reduce hospital admissions. There were no relevant short-term adverse effects that were any different from those seen with an inactive placebo, while long-term safety was not assessed. Further research is needed to confirm the efficacy, safety and applicability of this promising approach.
The evidence was current to December 2013. We found four randomized clinical trials involving 210 participants aged from one day to 17 years with PH either in the preoperative (one study) or postoperative period (three studies). Control groups received conventional management therapy (two trials) or nitrogen gas as placebo (two trials). Two trials compared changes in systemic and pulmonary arterial blood pressure and heart rate (haemodynamics). The other two trials compared the number of pulmonary hypertensive crises and deaths, with changes in haemodynamic measurements as secondary outcomes. We found no differences between the groups of patients who received iNO and those that did not. Two trials reported on deaths before discharge, with none occurring in one of the trials. We observed no differences in the number of deaths (two trials); pulmonary hypertensive crises (one trial); changes in mean pulmonary arterial pressure (three trials), arterial pressure (three trials), or heart rate (HR) (three trials); or changes in oxygenation of the blood (one trial). However, no trials reported long-term deaths or neurodevelopmental disability. In addition, no data were available for analysis of length of hospital stay. Although iNO has been studied as a postsurgical therapy in children with heart disease in order to assist recovery, this review showed no benefits with its use. Two trials had a low risk of bias. The quality of the evidence was, however, very low due to the small number of participants and low event rates. All trials utilized different concentrations of iNO, different durations of administration initiated at different times after the operation, and included patients with diverse congenital heart defects necessitating repair.
We found only one multicentre randomized controlled study, reported as an abstract in conference proceedings, that was eligible for inclusion in this updated Cochrane review. The company sponsored study enrolled 182 patients in 65 centres. The trial was stopped early, before recruiting sufficient numbers of participants and before it could detect any clear differences between partial liquid ventilation and conventional mechanical ventilation (the control group). The number of deaths at 28 days was 22% of patients in the partial liquid ventilation group and 14% in the control group, the difference was not statistically significant; there was a wide variation in results and a clinically significant difference could not be excluded. There were other problems with the trial that made its results unreliable in terms of eligible patients, use of other rescue therapies, and that the measured outcomes were altered at least twice during the study; additional therapies such as high frequency ventilation or inhaled nitric oxide were allowed in the control group.
The quality of the studies was deemed to be moderate. Of the nine studies, one was sponsored by a pharmaceutical company and funding sources were reported for only two other studies. The included studies were heterogeneous, small in size and had short follow-up periods. The interventions studied included exercise, gabapentin, ropinirole, levodopa, iron dextran, and vitamins C and E (individually and in combination). All interventions reduced the severity of RLS compared to a control. Intradialytic aerobic exercise reduced the severity of RLS however the safety of this intervention is unclear. Resistance exercise did not improve sleep quality but improved the mental health component on a quality of life questionnaire. This improvement in mental health component was not significant when compared to no exercise or ropinirole. Ropinirole reduced the symptoms of RLS and improved quality of sleep without any reported side effects. Gabapentin and levodopa improved the symptoms of RLS; however there were several adverse events reported included lethargy, drowsiness and fatigue for gabapentin, and vomiting, agitation, headaches, dry mouth, and gastrointestinal symptoms for levodopa. Iron dextran infusion reduced the symptoms of RLS but was only significant up to two weeks after treatment. Vitamin C, E and their combination also reduced RLS symptoms with minimal side effects. Small size and short duration of follow-up were the major drawbacks of these studies. The small number of studies, small sample sizes and short duration of follow up make it difficult to draw any firm conclusions. The effects of aerobic exercise and other pharmacological agents on RLS are uncertain in haemodialysis patients. There is a need to perform high quality randomised studies to establish the best treatment for RLS in patients with CKD. Aerobic exercise and ropinirole may be suitable interventions for further evaluation.
This review evaluates the effectiveness of medical therapies for patients with irritable bowel syndrome (IBS). We considered studies involving bulking agents (a fibre supplement), antispasmodics (smooth muscle relaxants) or antidepressants (drugs used to treat depression that can also change pain perceptions) that used outcome measures including improvement of abdominal pain, global assessment (overall relief of IBS symptoms) or symptom score. We found that bulking agents are not effective for treating IBS. There is evidence that antispasmodics including cimetropium/dicyclomine peppermint oil, pinaverium and trimebutine are effective for the treatment of IBS. Antidepressants are effective for the treatment of IBS. The side effects of these medications were not evaluated in this review. Physicians should be aware of the limitations of drug therapies and discuss these limitations with their patients before prescribing medication for IBS.
We included 20 studies (involving 547 stroke participants) that investigated the effect of treatments for visual field defects. However, only 10 of these studies compared the effect of a particular treatment with no treatment. Three of these studies investigated a type of eye movement training designed to improve the lost visual field (a 'restitutive' intervention). Four of the included studies investigated the effect of scanning training, which involves training people to 'scan' across the space in front of them and into the 'lost' visual field, in order to better cope with their lost vision (a 'compensatory' intervention). Three of the included studies investigated the effect of wearing a special prism on a pair of glasses, which increases the amount a person can see on their affected side (a 'substitutive' intervention). One of the studies investigated the effect of specialised assessment by an orthoptist (a hospital-based vision specialist), compared to standard care. We searched for studies up to May 2018. Only two studies presented data relating to how treatment can improve stroke survivors' abilities in activities of daily living, and there was a lack of consistency across studies that limited our ability to draw clear conclusions. There was insufficient evidence to draw any conclusions about the effectiveness of restitutive interventions as compared to control. There was low or very low-quality evidence that scanning training may help improve quality of life, but may have no effect on other outcomes (including adverse events). There was low or very-low quality evidence that prisms may have an effect on ability to scan (look) for objects, but may cause a range of minor adverse events (particularly headache) and may have no effect on other outcomes. Limitations with the evidence meant that we could not draw any conclusions about the benefits of assessment interventions. The quality of the evidence was low to very low, and in general was insufficient to reach conclusions about the effects of interventions for people with visual field defects.
The screening test used in these trials to detect colorectal (bowel) cancer was the faecal occult blood test (FOBT). If the FOBT is positive, the bowels are examined closely with further diagnostic test (coloscopy, flexible sigmoidoscopy, double-contrast barium enema), but these tests often cause discomfort and can cause serious adverse consequences. As blood identified in faeces may be due to several reason (unrelated to cancer), it may cause people unnecessary stress and expose them to possible harm. This review found that FOBT screening is likely to avoid approximately 1 in 6 colorectal cancer deaths.
This review found that nursing programmes and interventions to manage breathlessness may produce beneficial effects and that some psychotherapeutic, psychosocial and educational interventions can play some role in improving the quality of life of patients. Counselling may help patients to cope better with emotional symptoms and reflexology can have some short-term beneficial effects. The main limitations of the included studies were the variability of the interventions, the way results were measured and the lack of 'blinding' (ensuring that those who are measuring the patients' outcomes are not aware of which treatment the patient actually received).
The purpose of this review was to assess the evidence for the effectiveness of omega-3 supplementation for core features of ASD and associated symptoms. We found only two small randomised controlled trials that evaluated omega-3 fatty acids for ASD. There is insufficient evidence that omega-3 fatty acids supplementation is an effective treatment for ASD. However, high quality large randomised controlled trials are needed before definite recommendations about this treatment can be made.
Eleven studies on 419 people with asthma or exercise-induced breathlessness were included in this review comparing vitamin C compared to placebo (no vitamin C). Most studies were in adults and one small study was in children. The small number of studies available for review and their different designs meant that we were only able to describe individual studies, rather than pooling the results together to get an average from the trials. The study design was not well described in most study reports and therefore it was impossible to determine risk of bias for most of the studies. There was very little data available in the trials for our key outcomes and this may indicate some selective outcome reporting. There was no indication of benefit from the studies that considered vitamin C in relation to asthma. However, it is not possible to form any clear conclusions on the basis of those studies at this stage. The review concludes that there is insufficient evidence currently available to evaluate the use of vitamin C as a treatment in asthma. Larger, well-designed research is needed to provide clearer guidance. There was some indication that vitamin C was helpful in exercise-induced breathlessness in terms of how easily people breathe and their symptoms; however, as these findings were provided by only very small studies they do not provide complete answers to guide treatment. Details of the way patients were allocated to receive vitamin C or not were not clearly described in 10 of the 11 studies and we considered this carefully in the review in relation to our level of uncertainty in interpreting the results. Taking this into account, together with the imprecision of the results, we judged the estimates of the usefulness of vitamin C as a treatment to be of either low or moderate quality in relation to asthma. Additionally, for exercise-induced breathlessness the three studies providing data to the review were small and we are mindful of the need to draw very cautious conclusions about the results. This plain language summary is current as of December 2012.
The review of one small trial found that apnea might be reduced in the first few days after treatment, but there were not enough infants studied to know if this was a significant effect. There is no evidence from this trial on longer term effects or less common adverse effects. More research is needed on the effectiveness, potential harm and long-term benefits or adverse effects of these drugs.
Ten studies met the inclusion criteria for the review, and nine studies provided information for the review. A total of 1014 participants received an enhanced recovery protocol (499 participants) or standard care (515 participants) in the nine trials. The decision on whether a participant received an enhanced recovery protocol or standard care was made using methods similar to the toss of a coin, ensuring that the participants in the two groups were similar. One additional trial (including 33 participants) also performed the same comparison but did not provide any information for this review. Most of the trials included persons who were healthy in aspects other than the condition requiring surgery. Eight trials incorporated more than one component of the enhanced recovery protocol. None of the trials reported long-term deaths, medium-term health-related quality of life (three months to one year), time to return to normal activity, or time to return to work. The difference between enhanced recovery protocols and standard care was imprecise for short-term deaths, percentage of people with major complications, total number of major complications, health-related quality of life and hospital readmissions. Enhanced recovery protocols had a lower percentage of people with minor complications, fewer minor complications, shorter length of hospital stay (approximately two days shorter hospital stay per person) and lower costs (cost savings of approximately USD 6300 per person) compared to standard care. Because the trials were of poor quality and did not include clinically important end points, future high quality studies are needed in this field. The quality of evidence was low or very low. As a result, there is a lot of uncertainty regarding the results.
This review of the evidence from one randomised controlled trial suggests there might be less short-term lung injury from high frequency oscillatory ventilation. However, more babies in this group developed haemorrhage in and around the fluid spaces in the brain (cerebral ventricles) and this harm might outweigh any benefit. More information is needed to clarify the balance between benefits and harms of high frequency oscillatory ventilation instead of conventional positive pressure ventilation for preterm infants with severe lung disease.
The objective of this review was to evaluate the benefits and harms of Chinese medicinal herbs for people with cholelithiasis. Though some Chinese medicinal herbs appear to be safe for people with asymptomatic, mild, or moderate disease, they have not been conclusively shown to have curative effects on gallstones due to the low methodological quality (high risk of bias) of the included trials. Thus, randomised clinical trials with low risk of bias should be conducted to assess the effects of Chinese medicinal herbs before they can be used widely in the clinic.
We included 20 studies (1936 participants) in this review which compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other nebulised medications through the different types of nebuliser. Some conventional nebuliser systems have faster air flows and smaller medication droplets. These systems decrease treatment time and deliver more medication into the lung than other conventional nebulisers which have slower air flows and larger medication droplets. Nebulisers using newer technologies, e.g. adaptive aerosol delivery or vibrating mesh technology, deliver the medication faster and may deliver more of the medication into the lung. These systems appear safe when used with the correct amount of medication, which may be different to that used in a conventional nebuliser system. Some studies suggest that people with cystic fibrosis may prefer these newer systems and may take more of their medication when using them. More research is needed into what dose of medication is needed and how these newer nebuliser technologies affect quality of life, burden of treatment, additional treatment needed and treatment costs.
The 68 included studies covered a very wide range of disease areas, including antenatal care, cancer, home safety, hypertension, podiatry, smoking cessation and surgery. Primary, secondary and community care were included. The size of the studies ranged from 15 to 14,467 participants. Studies came from 12 countries; there was also one multinational study involving 19 countries. The USA and UK dominated with 25 and 22 studies, respectively. The next largest contribution came from Australia with eight studies. Our search updated our 2010 review and is current to February 2015. We also identified six studies published after 2015 outside the search. The review includes 24 mock trials where the researchers asked people about whether they would take part in an imaginary trial. We have not presented or discussed their results because it is hard to see how the findings relate to real trial decisions.
The purpose of this review was to evaluate anabolic steroids as a means of treatment of weight loss in individuals with HIV infection. The review includes 13 randomized clinical trials in the primary analysis. The results suggested that anabolic steroids increased both lean body mass and body weight. However, the results were not consistent among individual trials and the average increase was small and may not be clinically relevant. Furthermore, the results need to be interpreted with caution as this meta-analysis was limited due to small sample sizes; short duration of treatment and of follow-up; and heterogeneity of the study populations, the anabolic interventions, and concomitant therapies.
Ten trials including 441 liver transplant recipients provided data for this review. The patients were randomised to receive different treatments or no treatment in these 10 trials. We found two other trials, but data were not provided. There were no significant differences in the proportion of patients who died or required retransplantation within 90 days or at maximal follow-up between the different treatment groups for any of the comparisons. There were no significant differences in serious complications, graft rejection, microscopic features of liver damage, or evidence of chronic hepatitis C recurrence between the different treatment groups or no treatment in any of the comparisons that reported these outcomes. None of the trials reported quality of life, liver failure, intensive therapy unit stay, or hospital stay. Life-threatening adverse events were not reported in any of the comparisons. There is currently no evidence to recommend preventive antiviral treatment to prevent recurrence of chronic HCV infection either in primary liver transplantation or retransplantation. All the trials were at high risk of systematic errors (ie, there was potential to arrive at wrong conclusions because of the way the trial was conducted) and random errors (there was potential to arrive at the wrong conclusions because of the play of chance). Overall, the quality of evidence was very low. Further randomised clinical trials with low risk of random errors and systematic errors are necessary to assess the long-term survival benefits for various treatment options in these patients. Such trials should include patient-oriented outcomes such as mortality, graft failure, graft rejections, and quality of life.
There have been surprisingly few investigations of treatments for SH in children and adolescents, despite the size of this problem in many countries. Providing therapeutic assessment may improve attendance at subsequent treatment sessions. Only one therapeutic approach - mentalisation - was associated with a reduction in frequency of repetition of SH. However this effect was only modest and the trial was small, which prevents us from being able to make firm conclusions about the effectiveness of this treatment. There was no clear evidence of effectiveness for compliance enhancement, individual cognitive behavioral therapy (CBT)-based psychotherapy, home-based family intervention, or provision of an emergency card, nor was there clear evidence for group therapy for adolescents with a history of multiple episodes of SH. Therapeutic assessment, mentalisation, and dialectical behaviour therapy warrant further investigation. While in a single small study, individual CBT-based psychotherapy appeared ineffective, further evaluation of this treatment is also desirable given the favourable results found in adults who SH. Given the extent of SH in children and adolescents, greater attention should be paid to the development and evaluation of specific therapies for this population.
This systematic review found three studies with a total of 319 participants with COPD and coexisting anxiety. All three studies assessed psychotherapy (CBT) with a co-intervention, versus the co-intervention alone. There was limited evidence showing some improvements in reduced levels of anxiety and improved quality of life in the psychotherapy group. It is important to note that the overall quality of the evidence was low and hence further research is needed to increase our confidence in this effect. A limitation of this review is that all three included studies recruited participants with both anxiety and depression, not just anxiety, which may confound the results. Further research is needed to establish whether this therapy will reduce hospital admissions and length of hospital stays, as this was not assessed in the current evidence base. Larger studies of longer duration need to be conducted. There are at least two more clinical trials currently ongoing for this question. Once they are published, the evidence from them could increase or decrease our confidence in the findings of this review.
The general quality of the studies was poor. The main findings of the review suggest that there is some evidence from one study for the use of an egg-free diet in infants with a suspected egg allergy who have positive specific IgE antibodies to eggs in their blood. Other studies that compared a dietary exclusion with ordinary diets did not test the people taking part to see if they were allergic to the foods concerned. There appears to be little benefit in eliminating cows milk from the diet or using an elemental (liquid diet containing only amino acids, carbohydrates, fat, minerals and vitamins) or 'few foods diet' for improving atopic eczema in people who have not undergone any form of testing. Three of the studies used soya based substitute which itself can be allergenic to people with atopic eczema. Adhering to elimination diets is difficult. The studies were performed in different populations with only one study describing the severity of the atopic eczema. The clinical relevance of changes in severity scores obtained in many studies is unknown.
After a wide search for randomised controlled trials, we found two studies to include in our review, which together involved 69 people with Bell's palsy. Our main measure of the effects of surgery was to be the recovery of paralysis at 12 months. The first study compared surgery with a steroid medicine and the second study compared surgery with no treatment. In the first study the surgery and no surgery groups appeared to have similar facial nerve recovery at nine months. The second study found no differences in recovery of the facial paralysis after one year, between the participants who had an operation and those who had no treatment. One participant who had surgery in the first study had mild hearing loss and vertigo (dizziness) afterwards. Both studies had limitations that could have affected the results. This review was first published in 2011. We updated the searches in October 2012 and found no new relevant studies. The review found that there was only very low quality evidence and that this was insufficient to decide whether an operation would be helpful or harmful for people with Bell's palsy. There is unlikely to be further research into the role of an operation because Bell's palsy usually recovers without treatment.
We included randomized studies of critically ill adults receiving treatment in intensive care units and in other critical care areas. We selected studies that included lateral positioning after a single turn or following repetitive turns. The duration of each body position was 10 minutes or longer. Comparisons included the other lateral position (opposite side), as well as supine (lying on your back), semi recumbent (lying on your back with your upper body elevated to a 45-degree angle) and prone (lying on your stomach) positions. Results We found 24 eligible studies. No studies reported on mortality. Two studies reported on pulmonary morbidity following cardiac surgery, but available data were insufficient for analysis. The other studies reported measures that we included to identify clinical adverse events. Most of these studies did not report results in a way that could be combined for review of evidence, and trial design was often dissimilar. We compared two studies of critically ill adults with unilateral lung disease (one 'bad lung' and one 'good lung'). Oxygen levels within the blood were lower for 'bad lung down' (side lying with the 'bad lung' lowermost). However, the sample was small, both studies were of poor quality and very low oxygen levels in the blood were not consistently found across studies. Therefore, results need to be viewed with caution. Conclusion We found no clear evidence on the effectiveness of routine lateral repositioning or the effects of a single turn for critically ill patients. Good quality studies are needed to find out whether routine lateral repositioning is still recommended for most critically ill patients, and whether one body position is best avoided for some.
Rimonabant is the first drug of a new class of medications that seems to reduce body weight and improve risk factors for diseases of the blood vessels and heart in people who are overweight or obese. We found four studies which evaluated weight loss, occurrence of disorders and adverse effects of treatment. The four studies involved 6625 people comparing rimonabant 20 mg with rimonabant 5 mg and placebo, in combination with a hypocaloric diet after one or two years of treatment. Greater weight loss and improvement in risk factors were seen after 20 mg of rimonabant. These results have to be interpreted with caution though, due to high discontinuation rates of study participants and the overall low quality of the included studies.  We conclude that: 1. average weight loss with rimonabant appears modest, and 2. more rigorous studies examining the efficacy and safety of rimonabant are required to fully evaluate the benefit risk ratio of this new drug.  In Europe, rimonabant is contraindicated for patients with severe depression and/or patients who are treated with antidepressive medications. Rimonabant is furthermore not recommended for patients with other untreated psychiatric conditions.
We searched the medical literature to investigate the benefits and harms of thyroid hormone therapy for adults with AKI of any cause who were in hospital and found two studies that involved 97 people. There were many differences between study populations, particularly participants' kidney history (some had their own kidneys; others had transplants); and the drugs that were investigated. These differences meant that we were unable to statistically evaluate (meta-analyse) study data. We found that risk of death from any cause was much higher among people with AKI who received thyroid hormone therapy compared with those who received placebo in one study; no deaths were reported in the second study. Thyroid hormone therapy was found to be no better or worse than placebo in changing patients' needs for kidney dialysis or transplant. People with AKI who received thyroid hormone therapy needed dialysis for longer than those who received placebo in one study, but no differences in AKI and dialysis durations were noted in the other. Lengths of stay in intensive care units and hospital were similar in both those who received thyroid hormone therapy and placebo in one study; but not reported in the other study. Neither study reported if any participants progressed to end-stage kidney disease. We had planned to analyse changes in kidney function and numbers of dialysis sessions, but data reporting was insufficient to make assessments. The included studies were few in number, small in size, and low in methodological quality. The available evidence suggested that use of thyroid hormone therapy was associated with worse outcomes in patients with established AKI, and therefore, use of these therapies should be avoided for these people.
We included 10 randomized controlled studies (1629 participants) that compared PJ and PG in people undergoing Whipple surgery. The studies' features were adequate to make feasible and the planned comparison between the two surgical techniques. The primary outcomes were pancreatic fistula and death. Secondary outcomes were duration of hospitalization, surgical re-intervention, overall complications, bleeding, abdominal abscess, quality of life, and costs. We could not demonstrate that one surgical procedure is better than the other. PJ may have little or no difference from PG in overall postoperative pancreatic fistula rate (PJ 24.3%; PG 21.4%), duration of hospitalization, or need for surgical re-intervention (11.6% versus 10.3%). Only seven studies clearly distinguished clinically significant pancreatic fistula which required a change in the patient's management. We are uncertain whether PJ improves the risk of clinically significant pancreatic fistula when compared with PG (19.3% versus 12.8%). PJ probably has little or no difference from PG in rates of death (3.9% versus 4.8%) or complications (46.5% versus 44.5%). The risk of postoperative bleeding in participants undergoing PJ was slightly lower than those undergoing PG (9.3% versus 13.8%), but this benefit appeared to be balanced with a higher risk of developing an abdominal abscess in PJ participants (14.7% versus 8.0%). Only one study reported quality of life; PG may be better than PJ in some quality of life parameters. Cost data were not reported in any studies. Most studies had flaws in methodological quality, reporting or both. Overall, the quality of evidence was low.
The review included 21 studies that reported clinical outcomes in very preterm or low birth weight infants. Reporting was incomplete for all outcomes. Searches for studies were conducted in June 2017. Higher amino acid intake did not affect survival in preterm or low birth weight infants. Not enough information is available to determine whether this had an effect on neurodevelopment. Higher amino acid intake was associated with lower rates of growth failure, increased head growth, and fewer premature eye problems (eye problems were not severe). Higher amino acid intake was also associated with increased levels of protein breakdown products (urea) and a lower incidence of high blood glucose levels. Higher amino acid intake did not affect survival but reduced the incidence of growth failure up to the time of hospital discharge. Higher amino acid intake may produce other effects, including an increase in head growth and a reduction in eye problems (retinopathy of prematurity), although these effects are uncertain. Evidence suggests that high amino acid intake may not be tolerated by all infants. Further research is needed to determine the optimal amino acid intake for parenteral nutrition and nutritional balance in preterm infants. Low-quality evidence suggests that higher AA intake in parenteral nutrition does not affect mortality. Very low-quality evidence suggests that higher AA intake reduces the incidence of postnatal growth failure, and that higher AA intake reduces retinopathy of prematurity, but not severe retinopathy. Evidence was insufficient to show whether higher AA intake had an effect on neurodevelopment.
These drugs were highly effective in animal studies. Individual clinical trials in stroke patients did not confirm benefit for any of the drugs, however. This review confirms that there are no overall benefits for these drugs in stroke, although only two of them have been tested in a large enough population to be reasonably confident that they have no major effects. Some drugs may be harmful. Over 11,000 patients have participated in trials of 13 different drugs that inhibit glutamate release or binding, but two-thirds of all data are from trials of just two drugs. For most drugs in this class, trials have been too small to provide conclusive evidence of harm or benefit. Major differences among individual drugs mean that it is impossible to conclude that all drugs with this mode of action are ineffective. Further trials remain justified, and several are ongoing.
This review found a small benefit in platinum-based chemotherapy over non-platinum therapy. It also found that platinum combinations may offer improved survival over single platinum and that cisplatin and carboplatin are equally effective. The trials were done when paclitaxel (an effective new drug) was not used routinely. The results therefore, will need to be looked at in the light of new evidence from paclitaxel trials.
Atrial fibrillation (AF) is an irregularity of the heartbeat that leads to blood clots forming in the upper chambers of the heart (the atria). These clots can break free and travel through the bloodstream to the brain and cause a stroke. Drugs that slow clotting, such as oral anticoagulants (warfarin and other coumarin derivates) and antiplatelet agents (aspirin and others), reduce the risk of stroke in patients with atrial fibrillation. In this review of eight randomized trials, including 9598 patients, oral anticoagulants are shown to reduce the risk of stroke in patients with non-valvular AF and with no prior stroke or transient ischemic attack by one-third when compared with antiplatelet agents alone. Antiplatelet agents reduce stroke by about 20% in AF patients compared with no therapy, offering a less efficacious therapeutic option for those deemed not eligible for anticoagulation therapy. The threshold of absolute benefit that warrants anticoagulation remains controversial and depends on patient's preferences and availability of optimal anticoagulation monitoring.
This review examined the effect of psychological interventions in patients with inflammatory bowel diseases (Crohn's disease and ulcerative colitis) on health related quality of life, emotional state and disease activity. Overall, 21 studies were included in the review, but not all provided sufficient data for the different study questions. All studies were of low methodological quality. Most studies examined combination therapies, often aimed at improving stress management. For example, a therapy might include patient information sessions, training in relaxation techniques and psychotherapy sessions, such as group therapy. Others were restricted to just providing information materials to patients. None of the included studies reported any side effects of psychological interventions. In adults, psychotherapy was not effective at 6 and 12 months for all outcomes (quality of life, emotional status/depression and relapse/disease activity), based on 3 studies. There was no difference by type of disease (Crohn's disease versus ulcerative colitis) or intensity of the therapy. In adolescents, there was a small positive effect for all outcomes (quality of life, coping, depression and anxiety), but only short term effects were reported in this group. Disease activity and relapse rates were not examined in adolescents. In adults, educational interventions were also not effective to improve quality of life and the course of the disease over 1 year, based on 5 studies. Generally, at this moment, it can not be recommended that all patients with IBD receive psychotherapy. We assume that adolescents, and patients with special needs (e.g. emotional problems) may benefit from psychological therapy. More research is needed to examine the effect of psychotherapy focusing on the individual psychological situation of IBD patients.
We searched for evidence on the 29th of January 2019 and identified three small randomised controlled trials (involving a total of 524 women) for inclusion in our review. The overall trial quality was low to moderate. The trials did not report the majority of outcomes of interest in this review, including outcomes relating to cost or use of resources. Compared with monitoring the mothers' blood glucose levels alone, the addition of ultrasound may make little or no difference to the risk of having a caesarean birth (2 trials, 428 women, low-certainty evidence). Very low-certainty evidence means that we are unclear about the results relating to the risks of the mother having blood pressure disorders during pregnancy (2 trials, 325 women). The included trials did not report on the important maternal outcomes of low blood glucose, or development of type 2 diabetes. Using ultrasound in addition to monitoring the mother's blood glucose levels may make little or no difference to the risk of the newborn baby having low blood glucose levels (3 trials, 524 women, low-certainty evidence). Very low-certainty evidence means that we are unclear about results relating to the risks of: having a baby that is large for gestational age (3 trials, 524 women); the baby's shoulders becoming entrapped in the birth canal (1 trial, 96 women); death or illness in the newborn baby (1 trial, 96 women); or the baby dying during pregnancy or birth (1 trial, 96 women). This review was based on limited evidence from three trials (involving 524 women). The trials did not report some important outcomes of interest to this review, and the majority of our secondary outcomes were also unreported. The certainty of the available evidence ranged from low to very low. There was insufficient evidence to evaluate the use of ultrasound (in addition to maternal blood glucose concentration values) to assist in guiding the medical management of GDM, and the effect on important short- and long-term outcomes for the mother or her baby, or the associated costs. Large, randomised trials are needed. Such trials could consider important short- and long-term outcomes (as listed in this review) for the mother, her baby, and resource use.
The ABI test is non-invasive and inexpensive and is widely used clinically; therefore, we have reviewed all available reports obtained from a wide search of databases of medical literature to estimate its accuracy in identifying PAD in people who experience pain on walking that goes away after rest. Two review authors independently assessed studies that met inclusion criteria of the review, including use of a cross-sectional study design; enrolment of participants with pain on walking that got better with rest; and use of duplex ultrasonography or angiography to check that results of the ABI test were accurate. One study met our criteria and provided data from 85 participants (158 limbs). Investigators compared the manual doppler method of measuring ABI with the automated method. Researchers provided only data for legs as opposed to data for patients; we were therefore unable to recalculate the analysis at the whole-participant level. In conclusion, we found little evidence about the accuracy of the ankle brachial index for diagnosing PAD in people presenting with exertional leg pain. The study included in our review had some flaws, and well-designed cross-sectional studies are needed to measure the accuracy of the ABI for diagnosing PAD in patients with early symptoms.
Researchers in the Cochrane Collaboration examined the research published up to 13 April 2015. We identified three trials conducted in Thailand, India, Peru and Brazil on adults with confirmedP. vivax malaria that randomized 453 participants. All adults received chloroquine (to clear the parasites in the blood) and some groups received either tafenoquine, primaquine or no further treatment. All were observed for recurrences of P. vivax malaria (up to six months) and all trials tested people for G6PD enzyme, and excluded patients who were deficient. Adults receiving tafenoquine at doses greater than 300 mg had fewer relapses than adults who had no further treatment (moderate quality evidence). Tafenoquine 600 mg may be better in relapse prevention than standard primaquine doses (low quality evidence). In patients who do not have G6PD deficiency, there may be little or no difference in adverse effects (low quality evidence). The drug is untested in children and pregnant women. The shorter treatment course is a practical advantage, but the longer half-life could may have more substantive consequences if given inadvertently to people with G6PD deficiency.
We retrieved seven trials involving 447 infants requiring hospitalisation for marked breathing difficulties. Six trials recruited infants from paediatric intensive care units and one trial from the emergency department. Four trials were supported in part by unrestricted grants from a manufacturer with a commercial interest in the results. The evidence is current to March 2015. Pooled results failed to demonstrate a reduction in the rate of emergency department discharge, in the rate of intubation to achieve respiratory support, or in the length of respiratory support. However, four trials involving 138 infants used a clinical respiratory score system, with increased severity receiving a higher score. The pooled results show that infants treated with heliox inhalation had a reduction in this respiratory score in the first hour. In a small subgroup of infants who were started on a nasal device providing a continuous positive airway pressure right from the start, because of the severity of their disease, heliox inhalation could reduce length of treatment. Each trial included in this review used a different method for delivering heliox. They also used different thresholds of clinical respiratory score for inclusion, and were often underpowered for the major endpoints. Further studies using a valid method of heliox application in addition to standard medical care are needed. Inclusion criteria must include a clinical severity score that reflects severe respiratory distress to avoid the inclusion of children who are not very sick, who may not benefit from heliox inhalation. Such studies would provide necessary information about the appropriate place of heliox in the management of seasonal pulmonary infection in infants.
We included eight studies involving 1562 children that compared oral homeopathic treatment to either placebo or standard treatment to prevent or treat respiratory infections in children. All studies investigated upper respiratory tract (from the nose to the windpipe (trachea)) infections, but one combined reporting of upper and lower respiratory tract (from the windpipe to the lungs and pleura (membranes covering the lungs)) infections, so the numbers of children with upper or lower infections is unknown. Three studies received funding from homeopathy manufacturers; one reported support from a non-government organisation; two received government support; one was cosponsored by a university; and one did not report funding support. Studies investigated a range of interventions for various illnesses and populations using different outcome measures, so only a small number could be combined for analysis. All moderate-quality studies (low risk of bias) showed little or no beneficial effects for homeopathic medicinal products, whether individualised by a trained homeopath or a standard, non-individualised commercially available therapy. Where results could be combined, there was probably little or no difference in benefit on short- or long-term cure, or in prevention of ARTI. Two low-quality studies (unclear or high risk of bias) showed some benefit of homeopathic medicinal products for a limited number of outcomes. One study showed a reduction in disease severity for the homeopathy group at some time points. The other study showed a reduction in number of respiratory infections over the following year in the treatment groups, although more than a quarter of participants were not accounted for in the results. There was no difference between homeopathy and placebo groups for parents' time off work, antibiotic use, or adverse effects. Consequently, there is no convincing evidence homeopathic medicinal products are effective in treating ARTIs in children. We are unsure about safety because data on adverse events were poorly reported. We rated evidence as moderate or low quality for most outcomes. Three outcomes provided very low-quality evidence because study populations and results differed significantly among studies; there were significant limitations in study design and reporting; and sample sizes were small.
We included seven trials with 744 people with cystic fibrosis of both sexes, any age and both mild and more severe lung disease. The trials lasted from 28 days to 27 months. We could not combine many results as trials used different treatments. Two trials compared tobramycin to placebo (a dummy treatment). Three trials combined oral ciprofloxacin and inhaled colistin in the experimental group but used different comparators - one compared the antibiotic combination to no treatment, one to inhaled tobramycin and the third to oral ciprofloxacin with inhaled tobramycin. Another trial considered inhaled tobramycin and compared 28 days of treatment to 56 days. The final trial compared regular cycles of inhaled tobramycin (plus oral ciprofloxacin or placebo) to only treating with inhaled tobramycin (plus oral ciprofloxacin or placebo) based on the results of cultures grown in the laboratory. Two small trials (38 people) treating early infection showed that after two months inhaled antibiotics were better than no treatment and eliminated Pseudomonas aeruginosa in most people. One of these trials reported for longer and suggested that this effect may last for up to 12 months. Another small trial (26 people) which lasted two years showed that treating early infection with a combination of inhaled and oral antibiotics was better than no treatment for eliminating Pseudomonas aeruginosa. A trial comparing 28 days of nebulised tobramycin solution for inhalation (88 people) to 56 days showed both were equally tolerated and successful at eliminating Pseudomonas aeruginosa. Four direct comparisons of oral or inhaled antibiotics (or combinations of both), including one with 223 people, did not find a difference between different antibiotic combinations. A recent trial in 306 children (aged up to 12 years) compared a regular cycle of inhaled tobramycin (with either oral ciprofloxacin or placebo) to treatment only when it was shown that a child was infected with Pseudomonas aeruginosa and showed that when children were given a regular cycle of inhaled tobramycin (with either oral ciprofloxacin or placebo) fewer of them grew Pseudomonas aeruginosa from their sputum. The trial report made an adjustment for age and did not show any difference in the number of times Pseudomonas aeruginosa was grown from samples between the groups, nor was there any difference in the length of time until the children had their next chest infection. Some trials were conducted up to 20 years ago and the results may not be applicable today. Some trials were small. All the trials had quite a short follow-up period, so we could not show whether treatment made people with cystic fibrosis feel better or live longer. Given the treatments compared in most of the trials, it would have been easy for people to guess which treatment they were receiving, which might have influenced some of the results. Two trials were supported by the pharmaceutical industry. Further research is still needed to see whether eliminating the bacteria completely improves the well-being and quality of life in people with cystic fibrosis and to establish which antibiotic combination provides the best way of eliminating Pseudomonas aeruginosa. Overall the quality of evidence was moderate to very low, meaning that further research is likely to change the estimate of the size of the treatment effect. Future, larger trials (with greater power) may show one treatment is more effective in eradicating Pseudomonas aeruginosa than another.
The review includes two randomised clinical trials with 493 participants. The risk of bias was low. Both trials compared recombinant human activated factor VII with placebo. The meta-analysis showed that the recombinant human activated factor VII does not seem to reduce mortality in patients with liver disease and suffering from upper gastrointestinal bleeding, irrespective of the grade of liver damage. The current evidence is insufficient to support or reject recombinant human activated factor VII for these patients.
Only three trials with 430 participants met our inclusion criteria; however, two of the trials (412 participants) only reported death and no other measures of how well the treatments worked. All three trials included supportive care (treatment to prevent, control, or relieve complications and side effects and improve comfort and quality of life) as a co-intervention. The trials assessed transarterial chemoembolisation (where anti-cancer drugs block the blood supply and treat the cancer through the vessels supplying the cancer), chemotherapy using sorafenib (a drug which blocks cancer growth), or a combination of transarterial chemoembolisation and sorafenib. It appeared that the trials followed participants for about 18 to 30 months from the initiation of treatment. Two trials were funded by the pharmaceutical industry; one trial did not report the source of funding. Over 18 to 30 months, 50% to 75% of participants died. There was no evidence of any difference between the people who received chemotherapy and those who did not receive chemotherapy. None of the trials reported complications, health-related quality of life (a measure of a person's satisfaction with their life and health), cancer recurrence, or length of hospital stay. Overall, there is currently no evidence for benefit of any active treatment in addition to supportive treatment for intermediate-stage hepatocellular carcinoma. There is significant uncertainty on this and further high-quality randomised clinical trials are required. The overall quality of evidence was low or very low and all the trials were at high risk of bias, which means that there is possibility of making the wrong conclusions, overestimating benefits, or underestimating harms of one treatment or the other because of the way that the trials were conducted.
Only randomised controlled trials were included in this review. These were studies where a group of participants were given one physiotherapy intervention and were compared with another group who received a different physiotherapy intervention. The participants were assigned to a group in a random fashion to reduce the potential for bias. A total of 43 randomised trials involving 1673 participants (average trial size of just 39 participants) were identified as suitable for this review. The trials assessed various physiotherapy interventions, so they were grouped according to the type of intervention being used (general physiotherapy, exercise, treadmill training, cueing, dance or martial arts). However, despite this grouping, the physiotherapy interventions delivered and the outcomes assessed varied so much that the results of the individual trials could not be combined. This review highlights that a wide range of different physiotherapy techniques have been tested to treat PD. Considering the small number of participants, the wide variety of physiotherapy interventions and the outcomes assessed, there is insufficient evidence to support the use of one approach of physiotherapy intervention over another for the treatment of PD.
The evidence is current to November 2019. We found one study (91 participants) comparing a continuous cisplatin infusion with a one-hour cisplatin bolus infusion in children with neuroblastoma. For the continuous infusion, cisplatin was administered on days one to five of the treatment cycle but it is not clear if the infusion duration was a total of five days. Only results from shortly after induction therapy were available. At the moment there is no evidence showing that the use of a different cisplatin infusion duration prevents hearing loss or adversely affects tumour response and adverse effects. No data were available for the other outcomes of interest (i.e. tinnitus, overall survival, event-free survival and quality of life) or for other (combinations of) infusion durations or other platinum analogues. We need more high-quality research before definite conclusions can be made about the usefulness of different platinum infusion durations to prevent hearing loss in children with cancer. The quality of the evidence was low.
This review sought to find out how such computer programmes, known as Interactive Health Communication Applications (IHCAs), might affect people with chronic disease. The review authors found that IHCAs improved users' knowledge, social support, health behaviours and clinical outcomes. It is also more likely than not that IHCAs improve users' self-efficacy (a person's belief in their capacity to carry out a specific action). It was not possible to determine whether IHCAs had any effect on emotional and economic outcomes. The included studies involved different IHCAs, with different characteristics, for a wide range of chronic diseases. There was variability in several of the outcomes, and the results should therefore be treated with some caution. There is a need for more large, high quality studies to confirm these preliminary findings, to determine the best type and best way to deliver IHCAs, and to establish how IHCAs have their effects for different groups of people with chronic illness.
We included 14 randomised controlled trials (5600 women) which compared high-dose chemotherapy versus conventional chemotherapy in women with early breast cancer and with a high risk of recurrence. We defined these as women with breast cancer that has spread to multiple local lymph nodes without any evidence of spread beyond local lymph nodes. All studies reported their source of funding. Eight studies were funded by non-profit organisations, one by a public health insurance company, one by industry sources and four by a combination of non-profit organisations and industry sources. Four of the studies reported that authors had no potential conflict of interest, six reported that one or more of their authors had received some kind of support from pharmaceutical companies, and four did not mention whether any of their authors had any potential conflict of interest. Using high-dose chemotherapy has little or no effect on increasing survival. Although rates of event-free survival were higher in the high-dose arm over three-year follow-up, this effect was not apparent at longer follow-up. Treatment-related deaths were much more common in the high-dose group. Side-effects were also more common and more severe in the high-dose group. We did not find an effect on the number of women developing second cancers. The evidence was of high quality.
The review found that people lying on ordinary foam mattresses are more likely to get pressure ulcers than those lying on a higher-specification foam mattress. In addition the review also found that people who used sheepskin overlays on their mattress developed fewer pressure ulcers. While alternating-pressure mattresses may be more cost effective than alternating-pressure overlays, the evidence base regarding the merits of higher-specification constant low-pressure and alternating-pressure support surfaces for preventing pressure ulcers is unclear. Rigorous research comparing different support surfaces is needed.
Approximately 1% of people in industrialised countries have a leg ulcer at some time, mainly caused by poor blood flow back from the legs towards the heart. Skin grafts, either using the patient's own skin, artificial skin or donor skin/cells, have been evaluated to see whether they improve the healing of ulcers. The review of trials found evidence that tissue-engineered skin composed of two layers increases the chance of healing. There was not enough evidence to recommend any other type of graft, and further research is required.
We found six small randomised controlled trials (enrolling 549 infants in total) that addressed this question. The trials generally were of good methodological quality, although study findings may be biased by the inability to blind caregivers and investigators to the type of intervention provided. These trials provided only limited evidence on the effects of the interventions on nutrition. Analysis of data from three trials revealed that infants in the percutaneous central venous catheter group needed about four fewer catheters or cannulae during hospitalisation. Combined data from all trials showed no evidence of an effect on risk of bloodstream infection. Use of central venous catheters has been thought to increase the risk of bloodstream infection in newborn infants, but this review of randomised trials found no evidence that this was the case. More trials are needed to determine which method is better for improving nutrition and growth and development in newborn infants.
We found 39 randomised controlled trials (involving 2441 participants) that investigated the use of vestibular rehabilitation in this group of disorders. All studies used a form of vestibular rehabilitation and involved adults who lived in the community with symptomatic, confirmed UPVD. The studies were varied in that they compared vestibular rehabilitation with other forms of management (for example, medication, usual care or passive manoeuvres), with control or placebo interventions or with other forms of vestibular rehabilitation. Another source of variation between studies was the use of different outcome measures (for example, reports of dizziness, improvements in balance, vision or walking, or ability to participate in daily life). Due to the variation between studies, only limited pooling (combining) of data was possible. The results of four studies could be combined, which demonstrated that vestibular rehabilitation was more effective than control or sham interventions in improving subjective reports of dizziness, and in improving participation in life roles. Two studies gave a combined result in favour of vestibular rehabilitation for improving walking. Other single studies all found in favour of vestibular rehabilitation for improvements in areas such as balance, vision and activities of daily living. The exception to these findings was for the specific group of people with BPPV, where comparisons of vestibular rehabilitation with specific physical repositioning manoeuvres showed that these manoeuvres were more effective in dizziness symptom reduction, particularly in the short term. However, other studies demonstrated that combining the manoeuvres with vestibular rehabilitation was effective in improving functional recovery in the longer term. There were no reports of adverse effects following any vestibular rehabilitation. In the studies with a follow-up assessment (3 to 12 months) positive effects were maintained. There was no evidence that one form of vestibular rehabilitation is superior to another. There is a growing and consistent body of evidence to support the use of vestibular rehabilitation for people with dizziness and functional loss as a result of UPVD. The studies were generally of moderate to high quality but were varied in their methods. This evidence is up to date to 18 January 2014.
Most of the trials of piracetam were undertaken many years ago and did not use methods which would be currently considered standard. Some of the studies suggested there may be some benefit from piracetam but overall the evidence is not consistent or positive enough to support its use for dementia or cognitive impairment.
We were not able to find any trials to include in this review. Trials addressing this issue should be structured and reported according to the CONSORT statement for improving the quality of reporting of efficacy and improved reports of harms in clinical research. Trial investigators should consider including the following outcomes in new trials: number of days to be free of fever, death, onset of pain crisis or complications of sickle cell disease following community-acquired pneumonia, diagnosis, hospitalization (admission rate and length of hospital stay), respiratory failure rate, and number of participants receiving a blood transfusion. Since no trials have been included in the review up until September 2016, we will still search for trials every two years, but will not publish an updated version of this review until any eligible trials are identified.
We searched scientific databases to find all published and unpublished studies of STPP compared with wait-list control, treatment as usual or minimal treatment up to July 2012. We searched for studies in adults over 17 years of age with common mental disorders being treated in an outpatient setting. We excluded people with psychotic disorders. We included 33 studies involving 2173 people. When the results of the studies were combined and analysed, we found that there was a significantly greater improvement in the groups of people who received STPP versus the control groups, both in the short-term (less than three months after treatment) and medium-term (three to six months after treatment). These benefits generally appeared to increase in the long-term. However, some results did not remain statistically significant in the long-term and, in addition, the studies varied in terms of their design, meaning that these conclusions are tentative and need confirmation with further research. The finding that a short-term psychological therapy treatment may be broadly applicable and effective is of importance in the atmosphere of current global healthcare and economic restrictions. The studies were of variable quality.
The evidence is current to October 2013. We found 10 randomized clinical trials involving 432 participants. The main limitation of our review was our inability to identify studies analysing intraoperative data. Six trials reported mortality. We pooled these data and found no differences between the group of patients who received PEEP and those who did not, but because of the small number of patients, and the fact that this outcome may be rare, these results did not allow us to make a conclusion about the effect of PEEP on mortality. Two results suggested some benefit of PEEP. First, oxygenation was better on the day after surgery in the PEEP group. Second, radiological imaging showed less atelectasis after surgery in the PEEP group. The studies that we found did not suggest that intraoperative PEEP causes harm. Because of the small number of studies, this finding is inconclusive. We performed calculations to predict how many more participants would be needed before reliable conclusions can be made about the effect on mortality of the application of PEEP. This number was 21,200. Evidence is currently insufficient to allow conclusions about how intraoperative PEEP affects postoperative mortality and respiratory complications. The quality of the evidence is very low because of poorly conducted studies, small numbers of participants and low event rates.
Two small studies and one large study were identified. The two small studies enrolled infants given caffeine as a preventative measure. Neither study demonstrated any decrease in apnoea or other short term complications. The one large study included a heterogeneous group of infants who received therapy for a variety of indications (prevention, treatment and avoidance of post-extubation apnoea of prematurity). In this overall population there was an improvement in clinical outcome at hospital discharge and developmental outcome at 18 to 21 months; however, these benefits could not be proven in the subpopulation who received prophylactic caffeine. A decrease in PDA was noted in this subpopulation.
Six family practice studies including over 6,600 back pain patients found 21 tumors (0.3%).  One study on back pain diagnosed in an emergency room and one on back pain in a spine clinic included 482 and 257 patients.  The family practice studies described 15 different questions and physical exam tests that have been used to screen for spinal tumors.  Most of the 15 were not accurate.  A previous history of cancer is a very useful indicator.  Other facts that may indicate cancer are age greater than 50, no prior history of back pain, and failure to improve after one month.  These are most likely useful when combined, or with other indicators such as a history of cancer.  By themselves, these three questions would result in over-testing of patients without cancer. The worst effects of low quality red flag screening are overtreatment and undertreatment.  If the tests are not accurate, patients without a tumor may get an x-ray, MRI, bone scan or CT scan that they don’t need—unnecessary exposure to x-rays, extra worry for the patient and extra cost.  At the other extreme (and much less common), it might be possible to miss a real tumor, and cause the patient to have extra time without the best treatment. Most of the studies were of low or moderate quality and did not use an MRI, the most accurate imaging test, to confirm the presence or absence of a tumor, so more research is needed to identify the best combination of questions and examination methods.
This review found four studies that evaluated the effectiveness of HIV/AIDS training programs aimed at traditional healers; information about two of these studies is not yet available. Both of these studies found that workshops improved traditional healer knowledge about HIV/AIDS. However, an assessment of behaviour change in one study found that a training program improved traditional healer behaviour in terms of managing patients, but not in reducing risky behaviours and referral practices. Although the studies evaluated reported some positive outcomes, they were not of high quality. It is therefore difficult to be certain about the efficacy of interventions for educating traditional healers in the fundamentals of STI and HIV medicine.
This review identified 19 studies involving a total of 2,159 participants that evaluated an intervention intended to improve adherence. Ten of these studies demonstrated a beneficial effect of the intervention. We found that interventions targeting practical medication management skills, those administered to individuals vs groups, and those interventions delivered over 12 weeks or more were associated with improved adherence to antiretroviral therapy. We also found that interventions targeting marginalized populations such as women, Latinos, or patients with a past history of alcoholism were not successful at improving adherence. We did not find studies that evaluated the quality of the patient-provider relationship or the clinical setting. Most studies had several methodological shortcomings.
This review includes 41 randomized trials with a total of 8928 participants. Oral 5-ASA was found to be more effective than placebo (fake drug) for maintaining remission. Although oral 5-ASA preparations are effective for maintaining remission in ulcerative colitis, they are no more effective than sulfasalazine (SASP) therapy. People who have become well can remain so by continuing to take either medication. There is no evidence that side effects are more frequent with one or the other medication. However, the side effects of 5-ASA may be notably less than those associated with SASP therapy. Common side effects associated with 5-ASA included flatulence, abdominal pain, nausea, diarrhea, headache, dyspepsia (indigestion), and nasopharyngitis (inflammation of the nasal passages). Most of the trials comparing 5-ASA with SASP enrolled patients who were known to tolerate SASP. This may have reduced SASP-related side effects in these trials. Male infertility is associated with SASP and not with 5-ASA, so 5-ASA may be preferred for patients concerned about fertility. 5-ASA therapy is more expensive than SASP, so SASP may be the preferred option where cost is an important factor. Oral 5-ASA administered once daily is as effective and safe as conventional dosing (two or three times daily) for maintaining remission in ulcerative colitis. There does not appear to be any difference in efficacy or safety between the various formulations of 5-ASA. Patients with extensive ulcerative colitis or with frequent relapses may benefit from a higher dose of maintenance therapy. High dose therapy appears to be as safe as low dose and is not associated with a higher incidence of side effects.
Seven randomised controlled trials which included in all 199 participants are published. None fulfilled the presently accepted standards of a high-quality trial. All these studies have risks of bias and have a weak statistical power. Limited evidence from randomised controlled trials suggests that corticosteroids offer short-term benefit compared with placebo (dummy treatment). This supports the conclusions of observational studies and expert opinion. Limited evidence from randomised controlled trials does not show any difference in efficacy between corticosteroids and either azathioprine or intravenous immunoglobulin. All trials had design flaws which limit the strength of the conclusions. Further randomised controlled trials are needed.
We found 22 studies including 23,309 participants, comparing the long-term effectiveness and side effects of tiotropium and placebo. Compared with placebo, tiotropium treatment led to an improvement in quality of life, fewer people had an exacerbation (worsening of COPD symptoms), or exacerbations leading to hospital admissions. The number of people that needed to be treated for a year, for one person to avoid one additional exacerbation was 16 (95% confidence interval (CI) 10 to 36). We found no statistically significant difference between the tiotropium and placebo groups in terms of the number of hospital admissions for any cause, serious adverse events or deaths during the studies. However, when we divided the data depending on whether a dry powder inhaler or a soft mist inhaler was used in the studies, these two subgroups were significantly different. With the dry powder inhaler there were fewer deaths in the tiotropium group than in the placebo group, whereas with the soft mist inhaler there were significantly more deaths in the tiotropium group than in the placebo group. Also, there was a larger number of participants that stopped study medication early in the placebo group than in the tiotropium group. This review shows that treatment with tiotropium improves patients' quality of life, and reduces the risk of exacerbations, including exacerbations leading to hospitalisation. But tiotropium does not reduce hospitalisations for all causes or the number of deaths. Based on the evidence in this review, tiotropium appears to be a reasonable treatment choice for patients with stable COPD.
We searched the databases to 8 December 2014. We found seven randomized controlled trials (from 1992 to 2014) with 571 participants that met our inclusion criteria. Two of the seven trials involved 36 participants undergoing non-cardiac vascular surgery (infrarenal aortic surgery), and five involved 535 participants undergoing cardiac surgery, including valvular surgery, coronary artery bypass surgery, and cardiopulmonary bypass surgery. The interventions started from 11 days to 25 minutes before surgery in six trials and during surgery in one. All of the seven studies were conducted in Europe and the United States. One of the seven studies was funded by a drug company. Three trials involving 419 participants reported on deaths, but the results were imprecise with no evidence of a difference between the intervention and placebo groups (perioperative mortality). Two trials with 345 participants reported a similar number of participants in the two groups with changes in their electrocardiogram that indicated a heart attack (acute myocardial infarction). The output of the heart (cardiac index) appeared to be increased in one trial only. The two trials that reported the risk of low blood pressure as a potential complication of the intervention found no apparent difference; and the risk of stroke was similar with and without the intervention in three trials. The results from three studies showed that ACEIs or ARBs may reduce length of hospital stay, but these findings should be interpreted cautiously because of the possible influence of the clinical backgrounds of the participants studied. Two trials that assessed adverse events found no evidence of a difference between ACEIs or ARBs and placebo (no treatment). The quality of evidence for the outcomes was low or very low. The overall number of participants was small. Most participants were undergoing cardiac surgery, which meant the findings cannot be generalized to other types of surgery. We reran the search on February 3, 2017. We will deal with the three studies of interest when we update the review.
We reviewed evidence from randomised trials that assessed an educational intervention given after presentation in the emergency setting by adults over 17 years old. Thirteen trials involving 2157 people were included. The studies suggested that following the intervention there was a reduction in the frequency of future hospital admissions; however, the effect on visit to the emergency department was imprecise and the results of our analysis indicate that this was a chance result. Education may be an effective reinforcement strategy in reducing future hospital admission following emergency department attendance, but there was little evidence to suggest that it improved other indicators of chronic disease severity such as lung function and quality of life.
There are studies suggesting that bezafibrate, alone or in combination with ursodeoxycholic acid, is effective in treatment of primary biliary cirrhosis. Mechanisms through which bezafibrate improves lipid serum concentration balance and prevents biliary cell damage still need to be fully understood. This review evaluates all data on the benefits and harms of bezafibrate for patients with primary biliary cirrhosis in randomised clinical trials. The findings of this review are based on six randomised clinical trials with 151 Japanese patients. Bezafibrate was compared with no intervention in four trials (with co-intervention of ursodeoxycholic acid in both the bezafibrate and control groups) and with ursodeoxycholic acid in two trials. The primary findings of the review are that bezafibrate has no statistically significant effects on mortality, liver-related morbidity, adverse events, and quality of life of patients with primary biliary cirrhosis. A possible positive intervention effect of bezafibrate versus no intervention on liver biochemistry measures can be real but could also be due to systematic errors or random errors. The benefits and harms of bezafibrate for patients with primary biliary cirrhosis need further assessment in randomised clinical trials comparing bezafibrate with placebo. Such trials ought to be conducted with impeccable methodology to reduce the risks of random errors and sufficiently large patient groups to reduce the risks of random errors.
We searched scientific databases for clinical trials comparing the effects of amiodarone versus other antiarrhythmics or placebo on SCD, mortality and any side effects. We included adult participants at high risk or who had previously presented with sudden cardiac arrest, a serious heart malfunction that causes the arrhythmia. The evidence is current to March 2015. We found 24 studies comprising 9,997 participants. In participants at high risk, the evidence showed that amiodarone may prevent SCD or mortality when compared to placebo, and it is probably better than other antiarrhythmics. On the other hand, in participants who have already suffered a prior cardiac arrest, it is uncertain whether amiodarone increases or reduces the risk of a new episode of cardiac arrest or death. Furthermore, amiodarone may lead to or worsen adverse effects in the thyroid or lungs, when compared with placebo or other antiarrhythmics. The overall quality of evidence of these studies was low.
Nine randomised controlled trials involving 395 patients were evaluated. Six out of nine studies had a follow-up of less than one year, the longest study duration was 24 months. The overall quality of trials was variable, only a third of the analysed studies showed a low risk of bias. No information was available on quality of life, all-cause mortality and morbidity. Compared with conventional management, IGB did not show convincing evidence of a greater weight loss. The relative risks for minor complications, for example gastric ulcers and erosions were significantly raised.
This review evaluated the results of 17 trials (search dates August 2012 and October 2013), including 1,067 participants, that tested whether exercise programs could improve cognition (which includes such things as memory, reasoning ability and spatial awareness), activities of daily living, behaviour and psychological symptoms (such as depression, anxiety and agitation) in older people with dementia. We also looked for effects on mortality, quality of life, caregivers' experience and use of healthcare services, and for any adverse effects of exercise. There was some evidence that exercise programs can improve the ability of people with dementia to perform daily activities, but there was a lot of variation among trial results that we were not able to explain. The studies showed no evidence of benefit from exercise on cognition, psychological symptoms, and depression. There was little or no evidence regarding the other outcomes listed above. There was no evidence that exercise was harmful for the participants. We judged the overall quality of evidence behind most of the results to be very low. Additional well-designed trials would allow us to enhance the quality of the review by investigating the best type of exercise program for people with different types and severity of dementia and by addressing all of the outcomes.
The aim of this review was to evaluate the effects of sulpiride for schizophrenia compared to placebo (‘dummy’ treatment). Two short-term (12 weeks) studies with a total of 113 people are included. Information was limited and poorly reported. The inclusion of two small studies with small sample sizes meant that resulting data were not overly robust or meaningful. Overall no clear difference was noted between those receiving sulpiride and those receiving placebo for mental state or for leaving the study early. There was no information on other important outcomes, including: general functioning, service use, hospital admission, employment, family burden, satisfaction with care and side effects. The use of sulpiride seems to be based on clinical experience rather than strong evidence. Its widespread use in developing countries might have more to do with its lower cost than its effectiveness. Longer, well-planned, better conducted and reported randomised control trials would contribute to our knowledge about the effectiveness and potential side effects of this drug. This plain language summary has been written by a consumer Benjamin Gray: Service User and Service User Expert: Rethink Mental Illness. Email: [email protected]
The evidence is current to 25 August 2016. We included five studies with a total of 1231 participants with non-muscle-invasive bladder cancer. Four studies compared BCG given together with IFN-α versus BCG alone. One study compared BCG alternating with IFN-α versus BCG alone. The follow-up period in the studies ranged from two months to nearly 20 years. BCG combined with IFN-α (four studies):We found very low-quality evidence showing no clear difference in recurrence (four studies involving 925 participants) or progression (two studies involving 219 participants) between participants who received BCG combined with IFN-α and those who received BCG alone. None of the studies reported on the important outcome of stopping treatment due to adverse events. There was also very low-quality evidence showing no clear difference between groups for cancer-specific mortality (one study, 99 participants). There were mixed findings for adverse events (two studies, 120 and 670 participants, respectively). BCG alternating with IFN-α (one study):We found low-quality evidence showing a higher probability of recurrence when BCG was alternated with IFN-α compared with BCG alone (study involving 205 participants). We also found low-quality evidence that showed no clear difference in the probability of progression, risk of stopping treatment due to adverse events, and cancer-specific mortality between those participants receiving BCG alternating with IFN-α and those receiving BCG alone (one study involving 205 participants). There was also no clear difference between groups for overall survival or adverse events (one study involving 205 participants). None of the five studies reported on quality of life of the participants. As the included studies were often poorly conducted or reported, we rated the quality of the evidence as low overall. Further research is likely to have an important impact on our confidence in the accuracy of results.
In populations with a high risk of developing a new depressive episode in the next winter, results show that antidepressants can prevent winter depression in about one in four people. In populations with a lower risk of recurrence, antidepressants can prevent a new depressive episode in one of eight people. The other seven people suffer from winter depression despite treatment or would not have suffered from winter depression anyway. People using antidepressants are at slightly higher risk of experiencing headaches, nausea or insomnia when compared with people not taking antidepressants. Doctors need to discuss with patients the advantages and disadvantages of antidepressants and other potentially preventive treatments for winter depression, such as light treatment, psychological therapies or lifestyle interventions. As no available studies have compared these treatments, the decision for or against preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Review authors recommend that future studies should directly compare antidepressants against other treatments, such as light therapy, psychological therapies or other drugs to determine the best treatment for preventing winter depression.
Four small randomised controlled trials involving 54 participants in total showed that 3,4-diaminopyridine improves muscle strength. This was determined by measuring the compound muscle action potential (CMAP) which is a test that records the amount of electrical activity generated in a muscle when it is stimulated by its nerve. Although the number of trials is relatively small, the quality of evidence from these trials is moderate to high, which supports the findings of this review. The changes are measured over days only. A single trial involving nine participants showed that intravenous immunoglobulin also improved muscle strength up to 8 weeks from treatment. Other possible treatments such as plasma exchange, steroids and immunosuppressive agents have not been tested in randomised controlled trials. Further trials of these treatments are needed.
We found 104 studies (including 111,653 participants) testing the effect of any type of telephone counselling. The participants were mostly adult smokers from the general population, but some studies also looked at teenagers, pregnant women, and people with long-term or mental health conditions. Some studies included participants who had called helplines that provide smoking counselling (quitlines). Other studies included people who had not called quitlines, but received calls from counsellors or other healthcare providers. Some studies provided telephone counselling alone, but many others provided telephone counselling along with minimal support such as self-help leaflets, or more active support such as face-to-face counselling, or with stop-smoking medication. The number of calls offered ranged from a single call to 12 calls. Some studies only recruited people trying to stop smoking, while others offered support even to those not actively trying to stop. Studies needed to compare groups whose participants had similar characteristics at the start of the study, to investigate whether the participants had stopped smoking for at least six months, and ideally would test whether people had quit with blood or urine tests. We judged few studies to be well designed and conducted. Most had at least one issue that could have affected the results. In people who had called helplines, providing additional telephone counselling increased their chances of stopping smoking from 7% to 10%. In people who had not called a helpline, but received telephone calls from counsellors or other healthcare providers, their chances of stopping smoking increased from 11% to 14%. In studies which directly compared more versus fewer calls, people who were offered more calls (three to five) tended to be more likely to quit than those who received only one call. Telephone counselling appears to increase the chances of stopping smoking, whether or not people are motivated to quit or are receiving other stop-smoking support. The overall certainty of the evidence was moderate, meaning that further research is likely to have an important impact on our conclusions.
We included all randomised controlled trials that compared adjustment of asthma medications by usual clinical care (control group) versus using exhaled nitric oxide. The participants included in the trials had asthma diagnosed as per relevant asthma guidelines. The evidence is current to June 2016, when the searches were last completed. We found seven studies in the searches. Of 1700 randomised participants, 1546 completed the trials. The studies varied in a few aspects including duration, cutoff levels used for altering medications based on fractional exhaled nitric oxide (FeNO), and the way each study defined exacerbations. The included studies ranged from 4 months to 12 months in duration. The FeNO cutoff values the studies used also varied. The levels used for decreasing medications ranged from 10 ppb to 25 ppb. Likewise, the levels used for increasing medications ranged from 15 ppb to 35 ppb in the included studies. The majority of the studies were industry supported. The mean ages of the participants ranged from 28 to 54 years old. In this review involving 1700 adults with asthma, we found that guiding the dose of asthma medications based on exhaled nitric oxide (compared to a control group) was beneficial in reducing the number of exacerbations (flare-ups) during the study period. However, we did not find a difference between groups for other asthma outcomes that impact on day-to-day clinical symptoms, hospitalisations, or inhaled steroid dose. Thus, using exhaled nitric oxide levels to adjust asthma therapy may reduce the risk of adults having an asthma flare-up but did not impact on day-to-day symptoms. The quality of evidence ranged from moderate when comparing the two groups for the exacerbation outcomes, to very low when comparing the groups for inhaled corticosteroid dose at final visit.
Cochrane authors conducted a review including 61 randomised controlled trials comparing 18 different antioxidants with placebo, no treatment or another antioxidant in a total population of 6264 subfertile men. The age range of the participants was 18 to 65 years; they were part of a couple who had been referred to a fertility clinic and some were undergoing fertility treatment. The evidence is current to February 2018. Antioxidants may be associated with an increased live birth and clinical pregnancy rate. Based on the studied population for live birth, we would expect that out of 100 subfertile men not taking antioxidants, 12 couples would have a baby, compared with between 14 and 26 couples per 100 who would have a baby if taking antioxidants. If studies with high risk were removed from the analysis, there was no evidence of increased live birth. In the people who were studied for clinical pregnancy, we would expect that out of 100 subfertile men not taking antioxidants, seven couples would have a clinical pregnancy, compared with between 12 and 26 couples per 100 who would have a clinical pregnancy if taking antioxidants. Adverse events were poorly reported. However based on three studies, we could conclude that miscarriage did not occur more often if taking antioxidants. The use of antioxidants could give more gastrointestinal upsets, meaning that we expect that out of 100 subfertile men not taking antioxidants, two would have gastrointestinal upsets compared to between two and nine men if taking antioxidants. Antioxidant supplementation taken by subfertile males of a couple attending a fertility clinic may increase the chance of a live birth, however the overall quality of evidence was low from only seven small randomised controlled trials. Low-quality evidence also suggests that clinical pregnancy rates may increase. Overall, there is no evidence of increased risk of miscarriage, however evidence of very low quality suggest that antioxidants may give more mild gastrointestinal upsets. Subfertile couples should be advised that overall the current evidence is inconclusive due to the poor reporting of methods, failure to report on the clinical outcomes live birth rate and clinical pregnancy, and furthermore imprecision due to often low event rates, high number of dropouts and small study group sizes. Further large well-designed randomised placebo-controlled trials reporting on pregnancy and live births are still required to clarify the exact role of antioxidants.
We did a computer search for trials that compared a birth control pill containing drospirenone and estrogen to a placebo ('dummy') or another birth control pill in treating premenstrual symptoms. We wrote to researchers to find other trials. We looked at whether the pills reduced symptoms and if side effects were reported. Women recorded their symptoms over time. We found five trials with 1920 women. Two trials compared a dummy pill to a drospirenone pill with low estrogen. All the women had PMDD, the severe form of PMS, before the trial. After three months, women on the drospirenone pill with low estrogen had less severe premenstrual symptoms than the group taking the dummy pill. Women in the drospirenone group said they could do more and had more social activities and friends. Women on the drospirenone pill had more nausea, bleeding between periods, and breast pain. These side effects are common with birth control pills. Three trials studied a drospirenone pill with more estrogen for treating less severe symptoms. These women did not all have PMDD. One compared the drospirenone pill to a dummy pill but did not have enough data for our review. Two compared the study pill to another birth control pill. The two-year study showed the groups were similar for premenstrual symptoms and side effects. The six-month study did not give enough data on the symptoms. A drospirenone pill with low estrogen seems to help premenstrual symptoms in women with severe symptoms (PMDD). The drospirenone pill worked a little better than the dummy pill, which also affected symptoms. We do not know if the birth control pill works longer than three cycles, helps women with less severe symptoms, or is better than other birth control pills. Longer and better studies with more women are needed to address these issues. Trials reports should be clearer about how the study was done.
This study shows that people treated this way do manage to stay out of hospital longer than people treated by conventional systems of care. There are also some data showing that although these systems are expensive to start off with, if they are successful at keeping people out of hospital, then the cost saving from this means that they are cheaper in the long run.
This review assessed data from fifty-one studies and found that paracetamol provided effective pain relief for about half of participants experiencing moderate to severe pain after an operation, including dental surgery for a period of about four hours. There were no clear differences between doses of paracetamol typically used. These single dose studies did not associate paracetamol with any serious side effects.
We found four randomised controlled studies, with 281 participants. Relaxation was compared with electroacupuncture, superficial needling, paced respiration, placebo and no treatment. The age range of participants was 30 to 77 years. These trials were conducted in Sweden, the UK and the USA. No study was funded by an agency with commercial interest in the results of the study. The evidence is current to February 2014. Evidence is insufficient to show the effectiveness of relaxation techniques as treatment for menopausal vasomotor symptoms, or to determine whether this treatment is more effective than no treatment, placebo, acupuncture, superficial needle insertion or paced respiration. No evidence indicates that relaxation reduces the number of hot flushes per 24 hours or their severity. None of the studies reported night sweats, sleep disturbances associated with night sweats or adverse effects as an outcome. The quality of the evidence was very low. The main limitations of identified evidence included lack of data, imprecision and failure to report study methods in adequate detail.
We judged the quality of evidence to be high in relation to one intervention: a type of brain stimulation called transcranial direct current stimulation (tDCS), which is not currently used within routine practice. This high-quality evidence shows that tDCS does not improve people's ability to perform activities of daily living. We judged the quality of evidence to be moderate for 48 comparisons (covering seven individual interventions) and low or very low for 76 comparisons. Reasons for downgrading the quality of evidence to moderate, low or very low include small numbers of studies and participants, poor methodological quality or reporting of studies included within reviews, substantial heterogeneity (variation) between study results and poor review quality or reporting of methods. We conclude that high-quality evidence related to the effectiveness of interventions to improve upper limb function is urgently needed, in particular for those interventions for which moderate-quality evidence currently suggests a beneficial effect.
We searched medical databases such as Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, conference proceedings and study registries (January 2000 to August 2017). No trial evaluated one TPO mimetic (romiplostim or eltrombopag) versus another. We found eight eligible trials (six included, two ongoing, one of which is completed but without final results for MDS patients) and we included 746 adult patients in our review. The trials were randomised, double-blinded and used either romiplostim or eltrombopag versus placebo. In four trials hypomethylating agents or immunomodulatory drugs were administered in combination to romiplostim or eltrombopag. Only adults were included. A meta-analysis of overall survival data was not possible, since data were too heterogeneous to pool. Instead of that, we analysed mortality data. There was no evidence for a difference between TPO mimetics and placebo in terms of mortality during study, transformation to AML, transfusion requirement, adverse events and serious adverse events. Thrombopoietin mimetics probably decrease the number of patients having bleeding events. In the study population, 713 out of 1000 in the placebo arm had a bleeding event, compared to 656 of 1000 (95% confidence interval (CI) 613 to 699) in the TPO mimetics arm. No trial evaluated health-related quality. The quality of evidence for the outcomes incidence of bleeding events and all adverse events is moderate due to high risk of bias (small sample sizes and imbalances in baseline characteristics in three trials, premature closure of two trials, selective reporting in one trial, industrial sponsorship). The quality of evidence for the outcomes mortality during study and transfusion requirements is low, due to imprecision through small number of events and high risk of bias. It is very low for the outcomes transformation to AML and serious adverse events, because of very small number of events, high risk of bias and heterogeneity between trials. Although this systematic review reveals a potential patient-relevant benefit regarding decreasing bleeding events for evaluated adult patients, future trials should focus on outcomes referring to safety, efficacy and quality of life aspects of TPO mimetics to test their everyday usage. The assumption of premature progress to AML could not be clearly verified. Because of the low number of included trials and small sample sizes, uncertainties of the findings in this review exist and demand further investigation with more trials and participants and longer follow-up periods.
We undertook this review to determine the effectiveness of NPPV in patients with severe acute asthma. Six randomised controlled trials were included in the review. Compared to usual medical care alone, NPPV reduced hospitalisations, increased the number of patients discharged from the emergency department, and improved respiratory rate and lung function measurements. The application of NPPV in patients with asthma, despite some promising preliminary results, still remains controversial. Further studies are needed to determine the role of NPPV in the management of severe acute asthma and especially in status asthmaticus.
Types of analgesia used to relieve the pain include paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs) included aspirin and naproxen, opioids including codeine and non-pharmacological methods such as transcutaneous electrical nerve stimulation (TENS). The results from 18 randomised controlled trials involving 1498 women, of which nine (750 women) had data that could be included in the review meta-analyses, indicated that aspirin and other NSAIDs including naproxen were more effective at relieving uterine cramping pain than paracetamol or a placebo. NSAIDs included naproxen, aspirin, ketorolac and flurbiprofen. Only naproxen is still used in women who are breastfeeding. Aspirin is not recommended for use by breastfeeding women as there is concern that it will be passed to the baby in the breast milk. Codeine was not always more effective than a placebo or NSAIDs in the included studies and can sedate breastfed babies. Women offered codeine for pain relief should be informed about the potential for adverse effects for their babies. Codeine should only be prescribed for breastfeeding women with after birth pain if there is no alternative and their breastfed infants should be closely monitored for sedation and signs of codeine toxicity. Information about the safety of the NSAIDs for breastfeeding women and their babies was limited. The majority of analyses in this review included only one study with small numbers of participants. The average year of the included studies is 1981 and therefore further research is recommended comparing NSAIDs currently available and known to be safe for women who are breastfeeding and their babies.
Results of the seven randomised clinical trials included in the review in which patients received standard immunosuppressive treatment (steroids, azathioprine, and cyclosporine or tacrolimus) with or without bile acids after liver transplantation, did not show any significant effects of bile acids on all-cause mortality, mortality related to rejection, acute cellular rejection, steroid resistant rejection, or need for retransplantation. One analysis suggested that bile acids might beneficially influence number of patients with chronic rejection, but was contradicted by the analyses. The evidence that the use of ursodeoxycholic acid might have beneficial effects on chronic rejection and length of hospitalisation is weak as it is produced from trials with high risk of bias and insufficient number of included patients. That bile acids seemed well tolerated, with no reports of serious adverse events, is good knowledge, but much more research is needed before their use is acquitted. None of the randomised clinical trials assessed the effects of bile acids on quality of life or cost-effectiveness.
This is an update of a review first published in 2014, updated in 2017. We searched for evidence from randomised controlled studies in November 2018. We identified 12 studies involving 944 women (type 1 diabetes: 660 women; type 2 diabetes: 113 women; in two trials (171 women) there was a mix of type 1 and type 2 diabetes. The trials were from Europe, USA and Canada. There were six comparisons. These were: continuous versus intermittent monitoring of blood glucose (four studies, 609 women); two different ways of self-monitoring (two studies, 43 women); self-monitoring at home versus hospitalisation to control blood glucose levels (one study, 100 women); blood glucose monitoring before a meal (pre-prandial) versus blood glucose monitoring after a meal (post-prandial) (one study, 61 women); automated telemedicine monitoring versus conventional care (three studies, 84 women); and constant continuous monitoring versus intermittent continuous monitoring (one study, 25 women), Continuous versus intermittent monitoring may reduce overall high blood pressure problems during pregnancy (two studies, 384 women, low-quality evidence). However, it should be noted that only two of four relevant studies reported data for this outcome. There was more evidence on high blood pressure and protein in their urine (pre-eclampsia), which showed no clear difference (four studies, 609 women). We also found no difference in the number of women having a caesarean section (three studies, 427 women; moderate-quality evidence). There was not enough evidence to assess infant deaths or the combined outcome of infant deaths and ill-health as these outcomes were based on single studies. Four studies received some support from commercial partners. The other comparisons of different ways of monitoring blood glucose levels were based on very small studies or single studies with very low-quality evidence that did not show any clear differences in outcomes. Although the evidence from randomised controlled studies suggests that continuous monitoring of blood glucose levels may be more effective in reducing high blood pressure problems during pregnancy, only two studies reported on this. There was no clear reduction for pre-eclampsia based on evidence from four studies. For other methods of glucose monitoring, the review showed that there is not enough evidence to say with any certainty which monitoring method for blood glucose is best. More research is needed to find out which other monitoring method is best at reducing the risk of complications for pregnant women with pre-existing diabetes and to confirm the effectiveness of continuous glucose monitoring.
The review of trials found that men using PGE1 reported more satisfactory sexual experiences. Higher doses gave greater benefits but also increased the adverse effects. The most common adverse effect is some pain, and men may prefer the urethral medication rather than injections.
Three trials examined the betamimetic drug ritodrine plus magnesium compared with ritodrine alone. The trials reported on adverse side effects, with inconsistency between the trials as to which treatment gave fewer severe side effects. Other outcomes were either not reported or not clearly different between treatment groups. One trial looked at ritodrine plus indomethacin versus ritodrine alone. There were no clear differences between groups for serious newborn ill health. Results for other outcomes were not clearly different. There were no clear differences between groups receiving ritodrine plus progesterone compared with ritodrine alone for most outcomes reported, although the time between giving the drugs and the birth was increased in the group receiving the combination of tocolytics. For other combinations of tocolytic agents, results did not demonstrate differences between groups. There were no trials of combination regimens using widely used tocolytic agents, such as calcium channel blockers (nifedipine) and oxytocin receptor antagonists (atosiban). Due to insufficient evidence, it is unclear if combination tocolytic regimens are more or less effective than using a single tocolytic drug, or if they have more adverse effects. Some widely used tocolytic drugs have not been examined in trials as part of combination regimens, so further research is needed.
To assess this, we searched for randomised controlled trials of workplace health promotion interventions that involved the use of a pedometer undertaken in employed adults. Between 30th January and 6th February 2012 we searched a range of electronic libraries and references of relevant papers, retrieving 3282 potential papers. We eventually included four studies in the review. One study compared pedometer programmes with an alternative physical activity programme, but there were important baseline differences between the intervention and control groups that made it difficult to distinguish the true effect. The three remaining studies compared pedometer programmes with minimally active control groups. One study observed an improvement in physical activity in the pedometer programme, but two other studies found no significant difference between the pedometer group and the control group. We could not combine these results together, as each study used a different measure for physical activity, so it is not clear what the overall effect is. Single studies found beneficial changes in body mass index, fasting plasma glucose, the mental component of quality of life and worksite injury associated with the pedometer programmes as opposed to the control group. However, none of the studies identified consistent differences between the pedometer programme and the control group for waist circumference, blood pressure and quality of life outcomes. In addition, we judged the majority of included studies to have a high risk of bias, mainly due to participants and staff knowing who was in the intervention and who was in the control group, attrition of participants and not having published a protocol prior to running the study. We conclude that there was insufficient evidence to assess whether workplace pedometer interventions are of benefit. There is a need for further high quality randomised controlled trials to be undertaken with a range of health outcomes and assessment in the long term.
The included study showed neither a clear effect in favour nor against agomelatine as a preventive treatment. In addition, the certainty of evidence for all outcomes was very low, making it impossible to draw any conclusions about the efficacy and safety of agomelatine for the prevention of winter depression. No evidence on melatonin for prevention of SAD was identified. Doctors need to discuss with persons with a history of SAD that currently evidence on agomelatine or melatonin for preventive treatment options for SAD is inconclusive, therefore treatment selection should be strongly based on peoples' preferences and reflect on the evidence base of all available treatment options. Review authors recommend that future studies should evaluate the efficacy of agomelatine or melatonin in preventing SAD and should directly compare these interventions against other treatment options, such as light therapy, antidepressants, or psychological therapies to determine the best treatment option for prevention of SAD.
Certain drugs might prevent this damage, but for many of these drugs, the review authors found no high quality evidence about whether they were effective in protecting the heart and they were unable to draw conclusions. For dexrazoxane, the review authors found 10 studies enrolling over 1600 patients. These studies provided evidence that dexrazoxane prevented heart damage without interfering with the anti-tumour effects of anthracycline treatment. Patients who got dexrazoxane with their anthracycline treatment had about one third of the risk of heart failure compared to patients who got anthracyclines without dexrazoxane. Dexrazoxane had no effect on survival. We can't be sure about whether it had any undesirable side effects.
We found one small study involving 162 women and their babies (searched date 31 May 2015). The quality of the study was very low to moderate for our outcomes. The study was too small to provide answers to our question as we were most interested in the chance of the babies being born too early, their health and whether they survived. We did find that mothers with multiple pregnancies were more likely to have a caesarean birth if they attended specialised multiple pregnancy clinics. There is insufficient good quality evidence to support the use of specialised clinics for women with multiple pregnancies. There is an urgent need for more good quality studies to answer this important question. A visual summary of some of the results from this review can be found here (on screen version) or here (for a printable version).
We included two trials, one run in the USA (in people who were clinically stable) and one run in Canada (in people who were having an exacerbation or respiratory flare up). A total of 78 people from these trials gave sputum samples. Bacteria from these samples were grown in either a liquid (34 samples) or biofilm (44 samples) with an equal chance of being grown in either one. Neither the individuals or their clinicians knew before or during the trial which method had been used for the sample from each person. A mixture of adults and children took part in the trials, with the average age being around 20 to 30 years. There were an equal number of men and women in both trials. Around half the people in the trials had two copies of the delta F508 gene and there were almost equal number of these in each group. Average lung function in both groups was similar. The main outcome of both trials was the decrease in the amount of bacteria in the sputum of people in each group after antibiotic treatment. There was no difference in the levels of bacteria found in the sputum or in the improvement in lung function between the two groups in either trial. In both trials, there was a similar number of individuals in each group who had either a mild or moderate side effect. There were no serious side effects reported by anyone in either study. The evidence does not show that one method of testing is better than the other and that people receiving antibiotics chosen on the basis of either method have equal chances of any side effects. The quality of the evidence was quite good as people had equal chances of being in either group and they did not know which testing group they were in. This means we don't think the trial results would have been affected because of this.
We included 10 clinical trials with 474 participants. Seven trials compared terlipressin and albumin versus noradrenaline and albumin. The remaining three trials compared terlipressin and albumin versus midodrine and octreotide, or octreotide alone, or dopamine. In total, 241 participants received terlipressin and 233 participants received other vasoactive drugs (drugs that change blood pressure; noradrenaline, octreotide, midodrine, or dopamine). In five trials, investigators specifically stated that they did not receive funding from organisations that could profit from the trial results. We did not have information about the funding source from the remaining five trials. Our analyses found uncertain evidence to support or refute terlipressin versus other vasoactive drugs in the treatment of hepatorenal syndrome when evaluating mortality or serious side effects. Our analyses suggested that treatment with terlipressin may have a beneficial effect on hepatorenal syndrome by reducing the number of participants with persistent hepatorenal syndrome. Additional analyses showed that the number of participants in the trials was too small for us to be sure about this. Accordingly, we found that important differences between terlipressin and other vasoactive drugs may be overlooked. We found that the evidence was of very low quality due to the high risk of bias and the small number of participants. We need additional large trials of a high quality to evaluate if terlipressin is more beneficial or safer than other vasoactive drugs.
In September 2016 we searched for randomised controlled trials (RCTs) that compared topical phenytoin against other treatments for treating pressure ulcers. We found three small RCTs that included a total of 148 people with pressure ulcers. The average age of participants in two studies was 45 years and 75 years in one study. Twenty-one per cent of participants had grade I ulcers (the least severe type, with swollen but unbroken skin) and 79% had grade II ulcers (slightly more severe). No one had grade III or IV ulcers (the most severe types). The trials compared topical phenytoin with three other treatments for pressure ulcers: hydrocolloid dressings, triple antibiotic ointment, and simple dressings. The results of one study suggested that hydrocolloid dressings may slightly improve ulcer healing compared to topical phenytoin. However, we are uncertain whether topical phenytoin improves ulcer healing compared to simple dressings. The study which compared topical phenytoin with triple antibiotic ointment did not report any outcomes of interest to this review. It is uncertain whether topical phenytoin improves ulcer healing for patients with grade I and II pressure ulcers. No adverse events were reported from three small trials and minimal pain was reported in one trial. The trials did not report on some other measurements that we were interested in, such as cost of treatment and quality of life. Two RCTs had a high risk of bias overall, which might have affected the results, and another RCT did not report sufficient details about how it was conducted. Further rigorous, adequately powered RCTs are needed to find whether topical phenytoin is a helpful medication for treating pressure ulcers. This plain language summary is up to date as of September 2016.
We identified 12 randomised clinical trials involving 798 people undergoing planned laparoscopic cholecystectomy. The trials compared different methods addressing the various controversies mentioned above. The choice of the method of administration of the local anaesthetic was determined by a method similar to the toss of a coin so that the treatments compared were conducted in participants who were as similar as possible. There were no deaths or serious complications in either group in the comparisons that reported these. None of the trials reported quality of life, the time taken to return to normal activity, or the time taken to return to work. The differences in hospital stay between the methods being compared was imprecise in all the comparisons that reported hospital stay. Although there were some differences in the pain scores on the visual analogue scale (a chart that rates the amount of pain on a scale of 1 to 10 cm), these differences were neither consistent nor robust to different methods of statistical analysis. The evidence currently available is inadequate to determine the effects of one method of local anaesthetic intraperitoneal instillation compared with any other method of local anaesthetic intraperitoneal instillation in low anaesthetic risk individuals undergoing elective laparoscopic cholecystectomy. Most of the trials were of high risk of bias, that is, there is possibility of arriving at wrong conclusions overestimating benefits or underestimating harms of one method or the other because of the way that the study was conducted. The overall quality of evidence was very low. Further trials are necessary. Such trials should include outcomes such as quality of life, the time taken to return to normal activity, and the time taken to return to work, which are important for the person undergoing the procedure and the people who provide funds for the treatment.
Many of these therapies have been tried in non-randomised studies, but we found only eight small randomised controlled trials (RCTs), involving 236 participants, that met our criteria for inclusion. Two trials with 22 and 11 participants (20 with antibodies against MAG) suggest that IVIg may sometimes produce short-term measurable benefit and is relatively safe, but the benefit is of doubtful clinical significance. No severe adverse effects related to IVIg were reported in these trials. A trial of cyclophosphamide and corticosteroids showed some mild benefit. Two trials of rituximab demonstrated a positive benefit of rituximab, but this evidence was of low quality because of small numbers of participants and concerns about the design of one of the two studies. Reported adverse effects of rituximab were few, and mostly minor. Other trials did not allow us to draw conclusions about the efficacy of other agents and reported few serious adverse events. We need large, well-designed RCTs to assess the efficacy of the existing and new therapies, and better ways for doctors and researchers to detect changes that people report in response to treatments. The evidence is up to date to February 2016.
We found 12 studies comparing low sodium levels in dialysis fluid with neutral or high sodium levels. Many studies were performed prior to 2000, studying technology and patients that are not always relevant today. Most were short-term studies, only lasting a few weeks. Our main findings in these studies were; that low sodium in dialysis fluid improves blood pressure and reduces gain of salt and water in between dialysis treatments, which are probably good things, but increases the number of cramps and low blood pressure events experienced by patients during dialysis, which are definitely bad things. The studies did not provide enough information about the participating patients for us to know which patients might benefit from low sodium dialysis fluid, and which patients might instead be harmed. The studies did not provide definitive information on the effect of low sodium dialysis fluids on heart structure and function, or patient quality of life and survival. We are uncertain about whether low sodium in dialysis fluid improves overall health and well-being for people on haemodialysis, since there are a mixture of probably good and bad effects, and available research studies were not designed (or designed well-enough) to learn about effects of the intervention on the heart or on overall patient health and well-being. Larger and up-to-date definitive studies are needed to evaluate the medium to long-term effects of low sodium levels in dialysis fluid, and better inform clinical practice.
No randomised controlled trials with sufficient numbers of patients fitted the review criteria. Trials identified found BtA to be superior to placebo as did large case-control and cohort studies, with around 90% of patients benefiting. The most common adverse effects affected the eyes and were short lived.
This review included 10 trials, totaling 1904 participants that investigated the effect of these drugs in people with SAH. Antifibrinolytic treatment does indeed reduce the risk of rebleeding, but does not improve survival or the chance of being independent in everyday activities. This may be due to an increase in one of the other common complications of SAH. We conclude that antifibrinolytic treatment should not routinely be given to people with SAH, but new randomised trials are needed to establish if short-term treatment might be beneficial.
This updated review includes 94 (62 new to this update) randomised controlled trials involving 9821 participants. Most participants were women living in their own home. Some studies included frail people residing in hospital or residential facilities. Many of the trials had flawed or poorly described methods that meant that their findings could be biased. Most studies only reported outcome up to the end of the exercise programme. Thus they did not check to see if there were any lasting effects. We chose to report on measures of balance that relate to everyday activities such as time taken to stand up, walk three metres, turn and return to sitting (Timed Up & Go test); ability to stand on one leg (necessary for safe walking in well lit and dark conditions), walking speed (better balance allows faster walking), and activities of daily living (Berg Balance Scale, comprising 14 items). These were our primary outcomes.   There were eight categories of exercise programmes. These are listed below together with those measures of balance for which there was some evidence of a positive (statistically significant) effect from the specific type of exercise at the end of the exercise programme. Some trials tested more than one type of exercise. It is important to note that the evidence for each outcome was generally from only a few of the trials for each exercise category.   1. Gait, balance, co-ordination and functional tasks (19 studies of which 10 provided data for one or more primary outcomes). Positive effects of exercise were found for the Timed Up & Go test, walking speed, and the Berg Balance Scale.   2. Strengthening exercise (including resistance or power training) (21 studies of which 11 provided data for one or more primary outcomes). Positive effects were found for the Timed Up & Go Test; standing on one leg for as long as possible with eyes closed; and walking speed.   3. 3D (3 dimensional) exercise (including Tai Chi, qi gong, dance, yoga) (15 studies of which seven provided data for one or more primary outcomes). Positive effects were found for the Timed Up & Go Test; standing on one leg for as long as possible with eyes open, and with eyes closed; and the Berg Balance Scale.   4. General physical activity (walking) (seven studies of which five provided data for one or more primary outcomes).   5. General physical activity (cycling) (one study which provided data for walking speed).   6. Computerised balance training using visual feedback (two studies, neither of which provided data for any primary outcome).   7. Vibration platform used as intervention (three studies of which one provided data for the Timed Up & Go Test). 8. Multiple exercise types (combinations of the above) (43 studies of which 29 provided data for one or more primary outcomes). Positive effects were found for the Timed Up & Go Test; standing on one leg for as long as possible with eyes open, and with eyes closed; and the Berg Balance Scale. In general, effective programmes ran three times a week for three months and involved dynamic exercise in standing. Few adverse events were reported. The review concluded that there was weak evidence that some exercise types are moderately effective, immediately post intervention, in improving balance in older people. However, the missing data and compromised methods of many included trials meant that further high quality research is required.
This review found seven studies which evaluated whether these other services helped children and young people with mental health problems.  This review did not find any studies about intensive day treatment (where children attend treatment programmes during the day for a short period of time), intensive case management (health care professionals coordinate services and support for the children), therapeutic foster care (children live with specially trained foster parents) or residential care with inpatient care (children live in a residence, but not a hospital, which provides mental health care services). The studies evaluated four different types of services.  In Multisystemic therapy (MST) at home, therapists provide therapy to the child and the family together in their home.  Some behaviours in the children, improved with MST.  They also spent fewer days out of school and in hospital. Intensive home treatment provides children with therapy in their home to solve problems with the way they interact with other people in the home and to improve their psychological symptoms.  Children who received this type of service did not improve any more than children who did not.  Intensive home based crisis intervention (Homebuilders model for crisis intervention), focuses on the child and family to learn skills in relationship building, reframing problems, anger management, communication, and cognitive behavioural therapy.  Children with this service had small improvements. Specialist outpatient services are provided by a range of health care professionals in clinics.  Children who received this service did not improve any more than children who did not. The quality of some of the studies was not high and most did not have enough people to evaluate the true effect of the services.  The evidence we now have provides very little guidance for the development of these types of services.
Cochrane researchers conducted a review of the effects of micronutrient supplements for people living with HIV. This is an update of a Cochrane Review previously published in 2010. After searching for relevant trials up to 18 November 2016, the review authors included 33 trials. Thirteen of these trials included people not on HIV treatment and were conducted in Thailand, Peru, and eight African countries. Nineteen trials included people on HIV treatment and were conducted in North America, Europe, Brazil, Singapore, Thailand, Botswana, and Uganda. One trial from China did not state whether people living with HIV were on treatment or not. Some trials looked at the effects of taking supplements with multiple micronutrients whereas others looked at supplementation with single vitamins or minerals. What are micronutrient supplements and how might they help people living with HIV? Micronutrient supplements contain vitamins or minerals, or both, that are essential to good health. Many of these vitamins play important roles in maintaining the human immune system, which helps to fight off infections. Infection with HIV causes a progressive destruction of the immune system, which leaves people vulnerable to frequent infections. Many people living with HIV, especially in low-income countries, are also undernourished and many consume diets deficient that these essential micronutrients. Supplementation could therefore help people living with HIV to stay healthy for longer by strengthening their immune system or assisting recovery from infections. What the research says Multiple micronutrients Providing a daily supplement that contains multiple vitamins and minerals may have little or no effect on reducing deaths in people living with HIV, whether they are taking antiretroviral drugs or not (low certainty evidence). Daily supplements may have little or no effect on HIV disease progression as measured by CD4 cell count (low certainty evidence) or HIV viral load (low or moderate certainty evidence). Single or dual micronutrients We do not know whether supplements that contain single vitamins or minerals reduce deaths (very low certainty evidence) or slow disease progression (very low/low certainty evidence) in people living with HIV. Supplementation with vitamin A, D, zinc, or selenium may improve the level of each vitamin in a person's blood, especially those with low levels before supplementation (low/moderate certainty evidence). These findings do not mean that an adequate dietary intake for people living with HIV is not important. It is also not a reason to deny micronutrient supplements for those in whom a deficiency has been clinically demonstrated, or who are unlikely to meet the recommended daily allowance of vitamins and minerals.
We included a total of nine randomised and quasi-randomised trials, which enrolled 544 infants. To our knowledge, no studies included in this review were funded by industry. No study reported on weight at three or six months. One study reported improved growth at three months of age in infants exposed to cycled light compared with those exposed to continuous bright light. Another study found no difference in weight at four months of age. Length of hospital stay was shortened with cycled light in the nursery compared with near darkness or with continuous bright light. Only a few outcomes reached statistical significance, which is likely to be due to the small number of infants enrolled in these studies, but trends for most outcomes (weight gain, incidence of retinopathy of prematurity, time spent crying) favoured cycled light over near darkness, and cycled light over continuous bright light. The quality of the evidence on outcomes assessed was low because the interventions could not be blinded to caregivers, and few infants were enrolled in these studies.
The evidence is current to July 2015. This review has included 12 trials with a total of 1249 participants. By type of chest physiotherapy, five trials tested vibration and percussion techniques in 246 participants, three trials tested forced expiratory techniques in 624 participants, and four trials tested slow flow techniques in 375 participants. Vibration and percussion techniques produce a thorax (chest) oscillation by fast compression or percussion with the physiotherapist's hands. Neither manoeuvre was shown to improve the clinical scores of patients with acute bronchiolitis in the trials. These techniques did not show improvements in respiratory measurements, time on oxygen therapy or length of hospital stay. There were no data on time to recovery from acute bronchiolitis, use of bronchodilators or steroids, or parents' assessment of physiotherapy benefit. The trials included in this review did not present data on adverse effects related to the intervention, but the literature cites cases of relevant adverse effects such as rib fractures related to these techniques. Forced expiratory techniques consist of suddenly increasing the expiratory flow by compressing the thorax or the abdomen. In participants with severe bronchiolitis, such techniques failed to reduce time to recovery or time to clinical stability when compared to no physiotherapy. They also failed to improve clinical scores, oxygen saturation or respiratory rates except in mild to moderate bronchiolitis patients. There were no data on secondary outcomes such as duration of oxygen supplementation, length of hospital stay, or use of bronchodilators and steroids. Two studies reported no significant differences in parents' impression of the benefit of physiotherapy compared to controls. One of the trials reported a higher number of transient episodes of vomiting and respiratory instability after forced expiratory physiotherapy. This trial found no differences for bradycardias (decreases in heart rate), with and without desaturation (reduced oxygen levels in blood). Slow flow techniques consist of compressing the rib cage and the abdominal cavity gradually and gently from the mid-expiratory phase up to the end of exhalation. Slow flow techniques showed an overall lack of benefit on clinical scores of severity of the disease. However, in two trials they provided either a short-lived relief in terms of clinical scores or a decrease in the need for oxygen support in children with moderate bronchiolitis. There were no changes in length of hospital stay, use of bronchodilators or steroids. There were no data on changes in time to recovery, change in respiratory measurements, or parents' impression of physiotherapy benefit. No severe adverse events were reported in the trials. Vibration and percussion techniques are not recommended in routine practice in hospital settings due to a lack of benefit and risk of potential adverse events. There is high quality evidence that forced expiratory techniques in severe bronchiolitis present no clinical benefit, while being related to adverse effects such as vomiting, bradycardia with desaturation, or transient respiratory destabilisation. There is low quality evidence that suggests that slow flow techniques do not provide a clear overall benefit, but could provide some transient benefits in some children with bronchiolitis. Except for one trial, related to forced expiration, the included trials are at unclear or high risk of bias. The risk of bias of the trials and the imprecision of the estimates led to the low quality of evidence for the effect of slow flow techniques on clinical scores. Further trials are needed before reaching firm conclusions.
The review authors found four randomised control trials of adequate quality evaluating the impact of zinc supplementation as an adjunct to antibiotics for pneumonia in children. These studies were conducted in Bangladesh, Nepal and India, in which 3267 children aged two to 35 months were randomly assigned to receive zinc or placebo. No serious adverse events were observed. Analysis did not show any significant effect on the clinical recovery of patients in terms of time-to-recovery from tachypnoea (respiratory rate > 50 breaths per minute) and time-to-recovery from chest indrawing. It also showed non-significant effects of the intervention on the time-to-hospital discharge. Evidence provided in this review is insufficient to recommend use of zinc as an adjunct to standard antibiotic therapy for pneumonia in children aged two to 35 months.
The review of trials found that exercise training (including running, gymnastics, cycling, swimming, weights and walking) was well tolerated among the study participants. This review also found that physical training improved cardiopulmonary fitness and showed some positive effects for health-related quality of life. However, physical training had no significant effect on resting lung function. In summary, people with stable asthma should be encouraged to participate in regular exercise training that is within their capacity without fear of worsening of their asthma symptoms.
We found five studies including 1146 adolescents with asthma. Studies varied by design, duration (2.5 to 9 months), setting (school, day camp, primary care) and the way that peer support or lay-led sessions were given. Asthma severity varied, as did the number who smoked. Three studies used a programme called Triple A (Adolescent Asthma Action), by which older adolescents are trained to deliver sessions to younger students; one of these studies tested the addition of a pledge to stop smoking; another delivered peer support group sessions including messages played through an mp3 player to encourage adherence; and the third compared an asthma day camp led by peers against one led by nurses and doctors. Adolescents who received peer support had better quality of life than those in the control group, although this varied with how results were analysed, so we were uncertain. Most other outcomes did not show an important benefit of the intervention. These studies provided very little information about asthma attacks or unscheduled visits during the trial, and we couldn't be sure whether the intervention was beneficial in terms of asthma control. Results from two studies in which a lot of the adolescents smoked showed some promise that adolescents had the confidence to stop, but overall nicotine dependence and smoking-related knowledge were not much better than in controls. Studies provided no reports of adverse events. We can't be sure of the results because most outcomes were rated by people who knew the group to which adolescents were assigned, and this can affect how people behave and respond to questions. Some studies didn't report everything they said they would, or reported information that we could not analyse. Sometimes study results didn't agree with results of other studies, and often we could not say for certain whether adolescents received benefit. For these reasons, we have low confidence in all study findings.
This review investigated the effectiveness of personal assistance versus any other form of care for adults with both physical and intellectual impairments. A literature search identified 2 studies that met the inclusion criteria, which included 1002 participants. They suggested that personal assistance may be preferred over other services; however, some people prefer other models of care. This review indicates that personal assistance may have some benefits for some recipients and their informal caregivers. Paid assistance might substitute for informal care and cost government more than alternative arrangements; however, the relative total costs to recipients and society are unknown.
The review found six studies examining two different triptans. The number of people in the studies was limited. Within 15 minutes of using subcutaneous sumatriptan 6 mg, almost 8 in 10 participants had no worse than mild pain, and 5 in 10 were pain-free. Within 15 minutes of using intranasal zolmitriptan 5 mg, about 3 in 10 had no worse than mild pain, and 1 in 10 was pain-free. Adverse events were more common with a triptan than with placebo but they were generally of mild to moderate severity. Cluster headache is an awful thing to have. More research on how to get better pain relief faster, and to more patients, would be welcome.
We included in this review trials comparing daily use of corticosteroids, delivered by any type of inhalation device for at least three months, versus placebo or non-steroidal drugs in children up to 18 years of age with persistent asthma. Twenty-five trials involving 8471 children with mild to moderate persistent asthma (5128 treated with ICS and 3343 treated with placebo or non-steroidal drugs) were included in this review. Eighty percent of these trials were conducted in more than two different centres and were called multi-centre studies; five were international multi-centre studies conducted in high-income and low-income countries across Africa,Asia-Pacifica, Europe and the Americas. Sixty-eight percent were financially supported by pharmaceutical companies. Meta-analysis (a statistical technique that combines the results of several studies and provides a high level of evidence) suggests that children treated daily with ICS may grow approximately half a centimeter per year less than those not treated with these medications during the first year of treatment. The magnitude of ICS-related growth reduction may depend on the type of drug. Growth reduction seems to be maximal during the first year of therapy and less pronounced in subsequent years of treatment. Evidence provided by this review allows us to conclude that daily use of ICS can cause a small reduction in height in children up to 18 years of age with persistent asthma; this effect seems minor compared with the known benefit of these medications for asthma control. Eleven of 25 trials did not report how they guaranteed that participants had an equal chance of receiving ICS or placebo or non-steroidal drugs. All but six trials did not report how researchers were kept unaware of the treatment assignment list. However, this methodological limitation may not significantly affect the quality of evidence because the results remained almost unchanged when we excluded these trials from the analysis.
Our review looked at data relating to 7803 kidney transplant recipients. We assessed the risk of bias in all studies and found that most were unblinded, about half did not report funding sources or how they randomised and allocated study participants. We found that the risk of acute rejection significantly increased with both steroid-reducing treatments among adults who received kidney transplants. There was no little or no difference in the numbers of deaths or loss of transplanted kidneys for both steroid-reducing strategies within five years after kidney transplantation. Side effects, such as infection, cancer or diabetes after transplantation did not differ between groups of patients whose steroids were discontinued compared with those who continued to take steroids. The effect of steroid withdrawal in children is unclear. There was no evidence to suggest a difference in patient mortality or graft loss up to five year after transplantation, but longer-term consequences of steroid avoidance and withdrawal still remain unclear.
We searched scientific databases from their inception to January 2017 and found 25 trials where people were randomly allocated to either a group receiving drug-eluting stents or a group receiving bare-metal stents. The 25 trials (26 comparisons) included 12,503 adults with a mean age of 60.8 years. The people receiving drug-eluting stents did seem to have a reduced risk of experiencing a serious adverse event compared with those receiving bare-metal stents, without affecting the risk of dying from any cause or specifically heart disease, or of having a heart attack. The serious adverse event likely to be avoided by those receiving drug-eluting stents seems to be repeat balloon angioplasty. No data were reported on quality of life or chest pain (angina) after receiving the stent. The evidence should be interpreted with caution, as we judged the quality to be low to very low due to limitations of the included randomised clinical trials. The reason for the very low-quality judgement was mainly due to all included trials being at high risk of bias. Consequently, the results may show more benefit of drug-eluting stents than the 'real life' effect would show. Furthermore, most of the outcomes in our review lacked sufficient statistical power. Future well-designed randomised clinical trials may therefore change the above-mentioned results.
The antifibrinolytic drugs evaluated in this systematic review were aprotinin, tranexamic acid and aminocaproic acid. We found nine studies that enrolled a total of 455 participants, aged 18 years or younger, who received either antifibrinolytic drugs or a placebo. Total enrolment in each study ranged from 36 participants to 80 participants. Two of the studies evaluated aprotinin, four tranexamic acid and four aminocaproic acid. One study compared aminocaproic acid with tranexamic acid. The other studies administered placebo to the control group. Studies that evaluated aprotinin and aminocaproic acid used high doses (when reported). Of the studies that evaluated tranexamic acid, two used high doses, one used low doses and one did not describe the dose given. Five studies evaluated idiopathic scoliosis (scoliosis with no known cause), and four evaluated both idiopathic scoliosis and scoliosis that occurred as the result of another disease, such as cerebral palsy. Of the nine included studies, five reported how long patients were assessed. Follow-up ranged from one to 10 days after surgery, or lasted for the participant's length of stay in the hospital. Two studies received grants from organizations of healthcare professionals, and one was sponsored by a pharmaceutical company. The remaining studies did not report sources of funding. Antifibrinolytic drugs reduced the amount of blood lost during, or immediately after, surgery, by 427 millilitres (mL) (more than a 20% reduction in blood loss) and the amount of blood transfused during the same period by 327 mL. The number of children who received transfusions, either through blood from a donor or through a combination of blood from a donor and their own saved blood, was also significantly decreased. We assessed the quality of the evidence for all of these findings as low or very low because of the small numbers of participants, some concerns about study designs and imprecision in study findings. No children included in any studies died, and very few adverse events were reported, although three children receiving placebo in one study developed a clot. However, these studies may not have adequately looked for adverse events, or study authors might not have reported them fully. Also, the number of children evaluated was too small and the time of follow-up too short to allow review authors to draw any conclusions about their safety. This systematic review showed that antifibrinolytic drugs reduce blood loss and decrease the number of children receiving blood transfusions and the amount of blood transfused, but the evidence supporting any of these findings is not very strong. The safety of antifibrinolytic drugs remains unclear.
We identified 12 randomised controlled clinical trials investigating perioperative control of blood sugar levels. The perioperative period is the time period surrounding a patient's surgical procedure, involving ward admission, anaesthesia, surgery and recovery, and includes the preoperative (before operation), intraoperative (during operation) and postoperative (after operation) phases of surgery. We included a total of 694 diabetic participants randomised to perioperative intensive glucose control and 709 diabetic participants randomised to conventional or regular glucose control in our analyses. The trials were conducted in all continents except for Africa. The mean duration of the intervention period varied from a few hours to 90 days. The mean age of the participants was 64 years. Despite attaining lower blood glucose concentrations during the perioperative period, intensive blood glucose control did not significantly reduce the risk of relevant postoperative outcomes such as infectious complications, death from any cause, cardiovascular complications, renal failure and length of intensive care unit (ICU) and hospital stay. Due to posthoc evaluation of data, there is some evidence that targeting intensive glucose control increases the risk of hypoglycaemic episodes, but confirmation is needed from additional studies. One study assessed health-related quality of life in 12/37 (32%) participants in the intensive glucose intervention group and 13/44 (30%) participants in the regular glucose control group, and did not show an important difference. None of the studies investigated the cost-effects of the interventions. Based on the results of our review, the best approach for how to handle blood glucose control during surgery in patients with diabetes mellitus is not clear. We suggest that insulin treatment regimens, patient- and health-system relevant outcomes, and time points for outcome measures should be defined in a thorough and uniform way in future studies.
In this systematic review, we included six randomised controlled trials comprising 568 adult patients. In summary, we found evidence that the addition of ATG reduced the occurrence of only the severe forms (grade II to IV) of acute GVHD with a number needed to treat (NNT) of 8 concerning grade II to IV acute GVHD and a NNT of 7 concerning acute GVHD grade III to IV. This means that eight or seven patients have to be treated with ATG, respectively, in order to prevent one case of severe acute GVHD. However, neither overall survival nor the overall occurrence rate of acute GVHD was improved by the use of ATG. Moreover, we did not find a difference between ATG treated patients and those who did not receive ATG regarding relapse of the underlying disease or non-relapse mortality. The effect of ATG on quality of life after stem cell transplantation, which would be an important issue, has not been evaluated in randomised studies so far.
We searched a number of electronic databases in April 2014 to ensure that the review was up-to-date. We included six studies in the review with a total number of 309 participants. Three studies examined anger management, one study examined assertiveness training and problem solving, one study examined 'mindfulness' based on meditation, and one study examined modified relaxation. All the studies were conducted in community settings apart from one, which was conducted in a forensic inpatient setting. Five of these studies were small, comprising between 12 and 40 participants, and one was a large study of 179 participants, which was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme. Information on funding was not available for the other studies. Follow-up data were available only for two studies. We found improved outcomes in five studies, including reduction in anger ratings and in aggressive incidents, at the end of treatment. One study found improvements in anger coping skills as reported by key workers at 16 weeks and 10 months, but no other long-term benefit. One large study did not find improvements in quality of life or reduced costs to health services. Due to differences in the types of interventions, populations and assessments, we could not combine the results of the studies. There was one large study which presented moderate-quality data on the outcomes of interest. The other included studies were small and of poor methodological quality. Based on a 'Grades of Recommendation, Assessment, Development and Evaluation' (GRADE) assessment, we judged the quality of evidence on the outcomes of interest to range from very low to moderate quality. Moreover, the diversity of the interventions and participant groups makes it difficult for us to draw firm conclusions about the effectiveness of any particular approach. Therefore, more good-quality studies with longer-term follow-up data are needed.
We searched for controlled trials in the Cochrane Tobacco Addiction Review Group specialized register, in June 2015. We also searched a number of electronic databases, including MEDLINE, EMBASE, PsycINFO and CINAHL, using a variety of names and spellings for waterpipe use ('waterpipe' or 'narghile' or 'arghile' or 'shisha' or 'goza' or 'narkeela' or 'hookah' or 'hubble bubble'). We searched for published and unpublished trials in any language, and especially in areas where waterpipe use is widespread. We identified three studies that tested behavioural methods to help waterpipe smokers to quit. Two were waterpipe-specific interventions and one was a non-specific tobacco intervention.One small, pilot study was set in the USA, and delivered a Powerpoint presentation online to 91 college students who were using waterpipe. One study was a secondary analysis of data from 264 waterpipe smokers who were part of a trial that enrolled people suspected of having tuberculosis from 33 healthcare clinics in Pakistan. Clinics were randomly assigned to deliver a behavioural intervention versus control (usual care), or a behavioural intervention plus medication (bupropion) versus control (usual care). The third study, set in Egypt, targeted both cigarette and waterpipe smokers, and was a community-based programme. In all three trials, the percentage of participants who stopped smoking waterpipe was higher in the intervention groups than in the control groups, although this was a statistically significant finding in only two of the trials. People who received either behavioural treatment or behavioural treatment plus buproprion were more likely to quit waterpipe smoking at six months follow-up than those who received usual care. Men smoking waterpipe in the Egyptian study were more likely to have quit at one year follow-up in the intervention villages than in the control villages. These studies provide support to suggest that cessation interventions may help waterpipe smokers to quit. However, further larger studies are needed to build on this. The trials were all rated at very low quality of evidence, as they were relatively small studies, with at least one high risk of bias.
We searched for trials evidence on 31 May 2015 and found 12 trials total involving 1586 women, some comparing ethanol with a placebo and others comparing ethanol with other tocolytics (in this instance, all betamimetics). The trials included in this review were considered to be mostly low quality studies. For our comparison of ethanol versus placebo control (two trials, 77 women). We found that ethanol was no better than placebo (sugar water) for any of the outcomes studied: birth <48 hours after trial entry (one trial, 35 women) or neonatal mortality (one trial, 35 women). Serious maternal adverse events and perinatal mortality was not reported. There was no differences between groups for other outcomes: preterm birth < 37 weeks or < 34 weeks, serious infant outcome, fetal alcohol syndrome/fetal alcohol spectrum disorder, or small-for-gestational age. We also compared ethanol with other tocolytic drugs (nine trials involving 1438 women; all trials studied betamimetic drugs). We found that ethanol was worse than other betamimetic drugs at postponing birth until after 34 weeks' gestation and led to a higher rate of low birthweight babies, babies with breathing problems at birth and neonatal death (although there was no clear difference in neonatal deaths when we restricted our analyses to the better quality studies), However, we did find that, compared to betamimetics, ethanol was associated with a trend for fewer maternal side effects that required stopping or changing the drug, though this result is based on three small trials. There were no differences in other secondary outcomes of preterm birth < 37 weeks, number of days delivery was delayed, or overall maternal adverse events. Overall, we found no evidence that ethanol was better than a placebo at postponing preterm labor and birth. Whilst there was some evidence to suggest that ethanol may be better tolerated than betamimetics, we found that ethanol was not as effective as betamimetics at postponing preterm labor and birth. None of the studies were long-term ones and thus none of them reported on the risk of giving ethanol on the babies developing fetal alcohol syndrome, which can cause mental retardation. There is no need for new studies to evaluate the use of ethanol for preventing preterm birth. However, it would be useful for long-term follow-up studies on the babies born to mothers from the existing studies in order to assess the risk of long-term neurodevelopmental status.
A systematic review of a particular diagnostic test for a disease aims to bring together and assess all the available research evidence. Bibliographic databases are usually searched by combining terms for the disease with terms for the diagnostic test. However, depending on the topic area, the number of articles retrieved by such searches may be very large. Methodological filters consisting of text words and database indexing terms have been developed in the hope of improving the searches by increasing their precision when these filters are added to the search terms for the disease and diagnostic test. On the other hand, using filters to identify records for diagnostic reviews may miss relevant studies while at the same time not making a big difference to the number of studies that have to be assessed for inclusion. This review assessed the performance of 70 filters (reported in 19 studies) for identifying diagnostic studies in the two main bibliographic databases in health, MEDLINE and EMBASE. The results showed that search filters do not perform consistently, and should not be used as the only approach in formal searches to inform systematic reviews of diagnostic studies. None of the filters reached our minimum criteria of a sensitivity greater than 90% and a precision above 10%.
This review included randomised controlled trials comparing the combination of psychotherapy and a benzodiazepine with either the psychotherapy or the benzodiazapine alone for people with panic disorder. We were able to include only three trials in this review. Two could be used in the comparison of the combination of psychotherapy and benzodiazepine versus psychotherapy alone and one in the comparison of the combination with benzodiazepine. These comparisons involved just 166 patients and 77 patients, respectively. These small numbers make it difficult to detect any differences between combination treatments and either treatment alone. The trials which compared the combination of treatments with psychotherapy alone (both using behaviour therapy) indicated no differences in response between the two approaches, either during the intervention, at the end of the intervention, or at the last follow-up time point. The trial which compared the combination of treatments with a benzodiazepine alone demonstrated no differences in response during the intervention. Although the combination of treatments appeared to be more effective than the benzodiazepine alone at the end of treatment, no significant differences were observed at the 7-month follow-up. Before evidence-based treatment recommendations are possible, more randomised controlled trials are required, comparing the combination of psychotherapy and benzodiazepines with either treatment alone, and involving enough people to be able to detect a true difference between the treatments if one exists.
This review asked the question "do steroid drugs help children admitted to hospital with asthma?" We found that steroids given by mouth or through an intravenous tube help children recover from acute asthma. The benefits may include earlier discharge or a shorter stay in hospital. Children were less likely to come back to hospital in the one to three months following the admission. However, the evidence was not overwhelming due to the limited number of studies available and different medicines used. Further research needs to concentrate on the best medications to use and the best route of administration.
We found two studies that included children with upper airway infections: one involved 558 children who were recruited from 61 general practices in England and Wales; and another of 269 doctors who provided data on 33,792 patient-doctor consultations in Kentucky, USA. Participants were children accompanied by an adult. One study trained general practitioners (GPs) to discuss written information with parents, and in the other, doctors distributed copies of government-sponsored pamphlets to parents. Both studies were funded by government bodies and one was also funded by Pfizer (a pharmaceutical company). Providing a booklet and explanation by a specially-trained doctor reduced the number of antibiotics children consumed by 20% (from 42% to 22%) without affecting parent satisfaction with consultation or numbers of return visits for the same illness. Compared to the doctor’s usual practice, two studies showed that providing a booklet reduced the proportion of children prescribed an antibiotic by 9% to 21%. When doctors were also given feedback on their antibiotic prescribing along with providing a booklet to parents, the proportion of children prescribed an antibiotic increased by 6% (from 44% to 50%). None of the included studies assessed if people were better informed, how long symptoms lasted, or if people had complications. Evidence quality was moderate to low. Doctors and parents knew when written information had been used. One study had a high risk of bias because study groups were not comparable at baseline, so we can be less confident of its findings. Studies were set in the UK and USA, so results are not applicable to lower-income countries, nor for different primary healthcare services, including settings where prescriptions are unnecessary to obtain antibiotics.
We identified 31 studies to July 2015 for inclusion in the review. These included a total of 2257 participants who had had a stroke more than one month previously. They all investigated acupuncture aimed at promoting recovery compared with no acupuncture or sham acupuncture. Outcomes included measures of daily activities (activities of daily living), neurological function, movement, cognition, depression, swallowing, pain, and quality of life. Most of the studies (29/31) were conducted in China; the studies varied considerably with respect to the time of stroke, specific techniques used, and the frequency of acupuncture. We found some evidence that acupuncture improved activities of daily living and a number of aspects of neurological function. However, these conclusions were based on studies with low quality evidence. No serious side effects were reported and there was no information on the effects of acupuncture on death or the need for institutional care. It proved difficult to reliably determine the quality of the evidence because of poor reporting of study characteristics. Therefore, we have described most conclusions as having low or very low quality evidence.
We last searched for evidence on 20 December 2019. We included one randomised trial from earlier searches. This trial randomly assigned people with colorectal liver metastases that could not be surgically removed, to one of three intervention groups: TAE (22 participants), TACE (19 participants), and a control group (20 participants) that received no active therapeutic intervention. Cancer Research Campaign, a non-profit organisation, provided a grant for the study; Pharmacia Ltd. delivered the Port-a-Cath arterial delivery systems and degradable starch microspheres. Trial participants were followed for a minimum of seven months. Mortality at 44 months from trial entry was 86% in the TAE group, 79% in the TACE group, and 95% in the control group. Median survival after trial entry was 7.0 months in the TAE group, 10.7 months in the TACE group, and 7.9 months in the control group. Median survival from diagnosis was 8.7 months in the TAE group, 13.0 months in the TACE group, and 9.6 months in the control group. Local recurrence was reported in 10 participants, without further details of their treatment group. None of the participants in the control group reported side effects; 82% of the TAE group experienced short-term pain, nausea, vomiting, and high temperature, which got better with symptomatic treatment, and there was one report of bruising at the puncture site. TACE recipients reported short-term nausea, with or without vomiting, after most of the treatment sessions, and short-lived pain or discomfort; there was one wound infection, and one case of deep vein thrombosis. All the results were inconclusive between groups. The evidence from one small randomised clinical trial showed neither beneficial nor harmful effects of TAE or TACE compared to no intervention, in people with liver metastases, measured by mortality. We did not find data on the other outcomes of interest. We judged the evidence to be of very low certainty. The identified trial was small, at high risk of bias, and with inconclusive results.
We prepared this edition of this review by updating the methods and searching for evidence from the medical literature on 14 September 2016. The review now includes 11 randomised controlled trials (with 5977 women) that compared episiotomy as needed (selective episiotomy) with routine episiotomy in terms of benefits and harms for mother and baby in women at low risk of instrumental delivery. The trials were from ten different countries. In women where health staff were only conducting selective episiotomy, there may be 30% fewer with severe perineal trauma at birth compared with women where a policy of routine episiotomy was applied (eight trials, 5375 women, low-certainty evidence). We do not know if there is a difference in average blood loss between the groups (two trials, very low-certainty evidence). There is probably no difference in Apgar less than seven at five minutes, with no events in either groups (moderate-certainty evidence). We do not know if there is a difference in the number of women with moderate or severe perineal pain three days after giving birth (one trial, 165 women, very low-certainty evidence) but careful assessment of women's pain was not well carried out in the included trials. There may be little or no difference in the number of women developing perineal infection (two trials, low-certainty evidence); and there is probably little or no difference in women reporting painful sexual intercourse six months or more after delivery (three trials, 1107 women, moderate-certainty evidence); for urinary incontinence six months or more after delivery, there may be little or no difference between the groups. One study reported genital prolapse three years after the birth and there was no clear difference between groups (low-certainty evidence). Other important outcomes relating to long-term effects were not reported in these trials (urinary fistula, rectal fistula, and faecal incontinence). One trial examined selective episiotomy compared with routine episiotomy in women for whom an operative vaginal birth was intended. The results showed no clear difference in severe perineal trauma between the restrictive and routine use of episiotomy. Women's views on the different policies were not reported. Overall, the findings show that selective use of episiotomy in women (where a normal delivery without forceps is anticipated) means that fewer women have severe perineal trauma. Thus the rationale for conducting routine episiotomies to prevent severe perineal trauma is not justified by current evidence, and we could not identify any benefits of routine episiotomy for the baby or the mother. More research is needed in order to inform policy in women where an instrumental birth is planned and episiotomy is often advocated. Outcomes could be better standardised and measured.
This review aimed to assess the effectiveness and safety of acupuncture in slowing the progression of myopia in children and adolescents. We included two studies conducted in Taiwan with a total of 131 school children and did not combine the results as the two trials assessed different outcomes. One study found no significant difference in changes in the length of the eyes. Both studies found several children experienced mild pain while pressing and dropped out. The included studies in this review were unable to provide evidence of the effect of acupuncture for slowing the progression of myopia. More trials should be conducted where acupuncture is compared to placebo, other types of acupuncture are investigated, compliance with treatment for at least six months is explored and axial length elongation of the eye should be for at least one year.
We identified a total of six trials including 359 participants of whom 178 had primary closure and 181 patients had T-tube drainage after open exploration of the common bile duct. All six trials were at high risk of bias (risk of overestimating the benefits and underestimating the harms of the intervention or the control). There was no significant difference in mortality (12 deaths per 1000 participants in the T-tube drainage group versus 6 deaths per 1000 participants in the primary closure group) or in the serious complication rate after surgery between the two groups (approximately 145 complications per 1000 participants in the T-tube drainage group versus 66 complications per 1000 participants in the primary closure group). Although the number of deaths and complication rates in the primary closure group appeared to be less than half those in the T-tube group, there is a possibility that this was not a true observation but rather a difference that occurred by chance (similar to there being one chance in eight of flipping a coin and having it come up heads or tails three times in a row). For this reason we cannot be sufficiently confident that a true effect exists, and we term such a difference as not being statistically significant. None of the trials reported quality of life or the time taken for patients to return to work. The average operating time was significantly longer in the T-tube drainage group than in the primary closure group (by about 30 minutes). The average hospital stay was significantly longer in the T-tube group than in the primary closure group (by about five days). Use of a T-tube appears to increase the cost without providing any benefit to the patients. Further randomised trials with low risk of bias (low chance of arriving at the wrong conclusions because of prejudice by healthcare providers, researchers, or patients) and low risk of random errors (arriving at wrong conclusions because of chance) are necessary to confirm whether the use of T-tubes is justified anymore. Until the results from such trials are available, we discourage the routine use of T-tube after open common bile duct exploration.
We included 84 RCTs with 8234 participants in this review. Six trials (658 participants) did not report any of the outcomes of interest for this review. In the remaining 78 trials, 210 participants were excluded after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. Apart from the comparison of whether antibiotics should be used, the other comparisons included only a small percentage of people with pancreatic necrosis (an extremely severe form of pancreatitis, which results in pancreatic destruction). Most trials included only the severe form of acute pancreatitis or included both mild and severe forms of pancreatitis. Source of funding: seven trials were not funded or were funded by agencies without vested interest in results. Twenty-one trials were partly or fully funded by pharmaceutical companies. The source of funding was not available from the remaining trials. The overall quality of evidence was low for all the measures because the trials were at unclear or high risk of bias (a systematic error or deviation from the truth that affects the results, favouring one treatment over another) and were small trials. As a result, further studies are required on this topic. Sixty-seven studies including 6638 participants reported short-term deaths. Overall, an average 12% of people who received only supportive care died. There was no evidence that any of the treatments decreased short-term deaths. There was evidence that various treatments might be beneficial in a number of outcomes; however, these results were not consistent, and we cannot make any conclusions as to whether any of the treatments may be beneficial. None of the trials reported health-related quality of life. In conclusion, based on low quality evidence, there is no evidence that any drug treatment added on to supportive care decreases short-term deaths. Future trials in participants with acute pancreatitis should include health-related quality of life, costs, and return to work as outcomes and should follow patients for at least three months (preferably for at least one year).
After searching the literature, we included 14 studies with a total of 1358 participants. We found studies that investigated various interventions for preventing falls: physical exercises; predischarge home visits for hospitalised patients; the provision of single lens distance vision glasses instead of multifocal glasses; a servo-assistive rollator; and non-invasive brain stimulation. Included studies conducted their investigations in early to chronic inpatient, outpatient, and community dwelling settings. None Exercises appear to reduce the rate of falls, but not the number of people falling post stroke. Among the studies that used exercises as an intervention condition, the majority of studies asked participants to solely perform exercises. One study offered exercises together with additional components, such as educational sessions about falls. Another study offered exercises together with a comprehensive risk assessment and subsequent referrals, such as a review by an optometrist or new shoes, leading to a personalised programme for preventing falls. Besides exercises, several other interventions aiming to prevent falls post stroke were investigated in the literature. One study administered non-invasive brain stimulation to people after stroke and the results showed a potential to decrease the number of people falling, but this study needs to be replicated before consideration in clinical practice. There is no evidence at the moment that predischarge home visits, single lens distance vision glasses instead of multifocal glasses or a servo-assistive rollator reduce the rate of falls or the number of people falling. None of the included studies reported serious harm related to the intervention conditions. In summary: there is little evidence that interventions other than exercises are beneficial for preventing falls in people after stroke. The main reason is that there were only a limited number of studies focusing on people after stroke or that included a stroke subgroup in the study. In addition, studies related to falling do not consistently follow known methodological guidelines, particularly in fall definition and time post stroke. More well-reported, consensual research with an adequate number of participants might further establish the value of exercises in reducing falling post stroke. The quality of the evidence regarding rate of falls and number of fallers ranged from very low to low across the five comparisons, meaning that we have very low to low certainty in these results. The main reasons for downgrading the evidence were the lack of blinding of fall outcome and the majority of comparisons including only one study.
This review found that fluconazole, used as a preventive drug, significantly reduced the number of invasive fungal infections in liver transplant patients. More studies are needed to determine how effective antifungal drugs are for pancreas, heart, kidney and lung transplant patients.
This review examined the research published up to the 14th of April, 2016, and identified 11 studies involving 1760 participants. Eight of the studies compared LVRS versus standard medical care, one compared two closure techniques (stapling vs laser ablation), one looked at the effect of buttressing the staple line on the effectiveness of LVRS and one compared a traditional approach to LVRS with a 'non-resectional' surgical approach. All participants completed a mandatory course of pulmonary rehabilitation/physical training before the procedure commenced. This review found that people undergoing LVRS were at increased risk of death at three months after the procedure. By the end of follow-up, death rates were lower for participants treated with LVRS than for those given standard medical care. Participants who were characterised by poor lung function with a particular distribution of diseased tissue in their lungs were at higher risk of death at three months and throughout one large study. One study identified a group of participants who responded better to LVRS than other participants, making them especially suitable for this treatment. The benefit of surgery for surviving participants was significant in terms of quality of life, exercise capacity and lung function, but costs of the procedure are relatively high, and patients had a greater chance of adverse events after the procedure. The quality of the data reported is low to moderate in nature owing to some methodological issues of the trials (lack of blinding, unclear risk of bias). The results presented in this review are largely dominated by one influential study, which accounted for 68% of the participants.
The review set out to compare studies where women receiving standard care were compared with women attending on a reduced number of occasions. We included seven randomised controlled trials involving more than 60,000 women. We assessed studies for risk of bias and graded the quality of the evidence. The trials were carried out in both high-income (four trials) and low- and middle-income countries (three trials). In high-income countries the number of visits was reduced to around eight. In lower-income countries many women in the reduced visits group attended for care on fewer than five occasions, although the content of visits was altered so as to focus on specific goals. In this review there was no strong evidence of differences between groups receiving a reduced number of antenatal visits compared with standard care on the number of preterm births or low birthweight babies (moderate-quality evidence). However, there was some evidence from these trials that in low- and middle-income countries perinatal mortality may be increased with reduced visits (low-quality evidence) although there may have been fewer admissions to neonatal intensive care but the evidence for this latter outcome was not strong. There was no clear difference between groups for our other primary outcomes including maternal death and hypertensive disorders of pregnancy (including pre-eclampsia). There was evidence that women in all settings were less satisfied with the reduced schedule of visits; for some women the gap between visits was perceived as too long. Reduced visits may be associated with lower costs.
We included trials that reported on the use of pharmacological, non-invasive brain stimulation, psychological, and combination therapy interventions to treat depression after stroke. Mean age of participants ranged from 54 to 78 years. Studies were from Asia (30), Europe (11), North America (6), and Australia (2). We included 49 trials (56 treatments) involving 3342 participants. Pharmacological treatments resulted in fewer people meeting the study criteria for depression and less than 50% reduction in depression scale scores at end of treatment. Psychological therapy reduced the number of people meeting the study criteria for depression at end of treatment. More people in the pharmacological treatment group reported central nervous system (in five trials) and gastrointestinal side effects (in four trials) than in the placebo groups. Information on side effects of other treatments was not provided. Estimates of treatment effects were imprecise due to small numbers in most studies and recruitment of people with very different baseline characteristics. We rated the certainty of evidence as very low due to these and other limitations in study design. Antidepressant drugs may benefit people with persistent depressive symptoms after stroke, but care is required in their use, as little is known about their side effects. Psychological therapy may offer a treatment option. Future research should include a broader group of people with stroke.
This review aimed to assess the effects of physical exercise for pregnant women in preventing glucose intolerance or GDM and was based on limited evidence from five randomised controlled trials. Two trials involved obese women. The trials provided data from 922 women and their babies and were of moderate risk of bias. The exercise programs including individualised exercise with regular advice, weekly supervised group exercise session or home-based stationary cycling, either supervised or unsupervised, had no clear effect on preventing GDM (three trials with 826 women screened at 18 to 36 weeks' gestation), or improving insulin sensitivity (five trials) compared with standard antenatal care with normal daily activities. Based on these limited data, conclusive evidence is not available to guide practice. Larger, well-designed randomised trials are needed. Several such trials are in progress. We identified another seven trials which are ongoing and we will consider these for inclusion in the next update.
Thirteen studies compared mepolizumab, reslizumab or benralizumab to a placebo in 6000 people with asthma, most with severe disease. We summarised the results as they related to the occurrence of asthma attacks requiring additional treatment, quality of life, breathing tests, effects on a blood biomarker, and side effects. We found that participants with severe asthma, who had high numbers of a certain type of inflammatory cell (eosinophils) in the blood, benefited from taking mepolizumab, reslizumab or benralizumab through reduced asthma attacks. There were small improvements in quality of life and breathing tests, but these may be too small to be detected by patients. We agree with international guidelines that say that these treatments can be added to standard treatment for people with severe asthma. However, we think that further research is needed to clarify some aspects, such as how to assess treatment response and how long to give treatment for. The evidence included in this review is provided by very well-designed studies. We consider these studies to be at low risk of bias in the following important respects: the procedure that determined who received which treatment, the blinding processes and the clarity of detail concerning participants who did not complete the study. Overall the evidence was high to moderate quality.
We found 71 relevant studies, but not all measured the outcomes we were interested in. Forty-two studies were included in the quality of life analyses (measured on St George's Respiratory Questionnaire), and 46 were included in the lung function analyses. Evidence from good quality and similar trials supported LABA/ICS combinations as the most likely treatment strategy to bring the greatest improvement to quality of life and lung function. Combination therapy gave an average benefit of 3.9 units over placebo at six months. LAMAs and LABAs were ranked second and third at six months (-2.63 and -2.29 units, respectively), especially when unreliable trials were not included, but a large degree of overlap in the estimates was noted. Combination LABA/ICS was the highest ranked class for trough forced expiratory volume in one second (FEV1), with mean improvement over placebo of 133 mL at six months (95% credible Interval (CrI) 101 to 164). As was the case for SGRQ, LAMAs (mean difference (MD) 104, 95% CrI 82 to 125) were ranked just ahead of LABAs (MD 99, 95% CrI 72 to 128) at six months, and ICSs were the lowest ranked class (MD 65, 95% CrI 33 to 97). For both outcomes, the effects of LABA and ICS used alone appeared to increase when used together for six months, but initial differences between the treatment classes were less obvious after a year of treatment. Quality of life and lung function were improved most on combination inhalers (LABA and ICS) and least on ICS alone at 6 and 12 months. Overall LAMA and LABA inhalers had similar effects, particularly at 12 months. The network has demonstrated the benefit of ICS when added to LABA for these outcomes in participants who largely had an FEV1that was less than 50% predicted, but the additional expense of combination inhalers and any potential for increased adverse events (which has been shown by other reviews) require consideration. Our findings are in keeping with current National Institute for Health and Care Excellence (NICE) guidelines.
We did a computer search for studies of birth control pills with two phases versus pills with three phases. We also wrote to researchers and manufacturers to find other trials. We included randomized trials in any language. We found only two trials that looked at two-phase versus three-phase birth control pills. The studies did not have good methods and the authors did not report all their methods. Many women dropped out of the studies, which affects what can be said about the results. One study compared two types of two-phase pills with a three-phase pill. The pills did not differ in any major ways, including the numbers of women who stopped using the pills due to health problems. The other trial compared a two-phase pill with two different three-phase pills. The two-phase pill had worse bleeding patterns than the three-phase pill with a different hormone (levonorgestrel). In contrast, bleeding with the two-phase pill was like that of the three-phase pill with the same hormone (norethindrone). The type of hormone may be more important than the phases for cycle control. These trials did not provide enough evidence to say if three-phase pills worked any better than two-phase types for birth control, bleeding patterns, or staying on the pill. More research would be needed to show whether three-phase pills were better than two-phase pills. However, two-phase pills are not used enough to justify further research.
Five observational studies with 7199 patients were used to compare endoscopic surveillance to non-surveillance. The key findings of the review were that a higher rate of cancer occurred in the non-surveillance group compared to the surveillance group, and that a lower rate of colon cancer-associated death was demonstrated in the surveillance group compared to the non-surveillance group. In patients undergoing surveillance, the odds of colon cancer development were reduced by 42% and the odds of death associated with colon cancer was reduced by 64%. Surveillance resulted in detection of a higher rate of early stage colorectal cancer in the surveillance group compared to the non surveillance group which may explain the improved survival seen with surveillance. The overall quality of the evidence is very low due to the nature of observation studies and the low number of events. Nonetheless, these results suggest that endoscopic surveillance in people with IBD may reduce the development of colon cancer through early detection and may also reduce the chances of dying from colon cancer.
The 31 included trials involved 1817 women from 14 countries. The studies included women with stress, urgency or mixed urinary incontinence. The women were allocated randomly to either receive or not receive PFMT and the effects were compared. We looked at whether the condition was 'cured,' or 'cured or improved.' We also looked at symptoms, the effect on quality of life (QoL) and the frequency and amount of urine lost. Eight studies were publicly funded. Three received grants from public and private sources. Two received grants from private sources, while two studies received no funding. Sixteen studies did not declare their funding sources. The quality of the evidence we looked at was mostly moderate, which means we can have some confidence in the results. Cure of urinary incontinence after PFMT: women with stress urinary incontinence in the PFMT group were, on average, eight times more likely to report being cured. Women with any type of urinary incontinence in the PFMT group were, on average, five times more likely to report being cured. Cure or improvement of urinary incontinence after PFMT: women with stress urinary incontinence in PFMT groups were, on average, six times more likely to report they were cured or improved. Women with all type of urinary incontinence in the PFMT group were roughly twice as likely to report they were cured or improved. Leakage episodes after PFMT: women with stress urinary incontinence and women with all types of urinary incontinence in the PFMT group had one fewer leakage episode in 24 hours. PFMT appeared to reduce leakage episodes in women with urgency urinary incontinence alone. For women with stress and all types of urinary incontinence, their incontinence symptoms and QoL were improved in the PFMT groups. Women were more satisfied with the PFMT treatment, while those in the control groups were more likely to seek further treatment. Negative side effects of performing PFMT were rare and, in the two trials that did report them, the side effects were minor. The authors of the one economic evaluation identified for the Brief Economic Commentary reported that the cost-effectiveness of PFMT looks promising.
Whether surgery is performed through a cut in the abdomen or a cut through the anus (known as a perineal approach), it makes no difference with regard to reappearance of the prolapse or appearance of postoperative complications. When surgeons perform the operation through a small hole in the abdomen (laparoscopic or keyhole surgery) recovery may be faster than for open abdominal surgery. When constipation is one of the main symptoms, bowel resection (removing part of the bowel) during prolapse repair may help. There was no difference in the results when different types of repair were used during the perineal (anal) approach. There was no particular concern about different types of surgery described in this review. Although 15 studies were included in this review, many of them had different comparisons and some had poor methods, limiting the usefulness of the findings. However, longer follow-up of patients in these studies, together with results from ongoing trials, may provide some information in the future.
This review shows that hydroxyzine is better than placebo in terms of anxiety symptoms in individuals with generalised anxiety disorder (GAD). Too few data were available to be able to draw any conclusions about the efficacy and tolerability of hydroxyzine compared with benzodiazepines and buspirone. Given the robust evidence for the efficacy of antidepressants for GAD, these findings suggest that hydroxyzine should not be recommended as first-line treatment GAD.
We included 52 studies involving 5077 people. These studies lasted between one day and three years. Most of the people included in the studies had mild asthma. Both males and females were included, and about half of the studies included only children. Most studies involved people with house dust mites or pollen allergy. The evidence presented here is current to 25 March 2015. Very few studies recorded the number of people who had asthma attacks leading to a hospital visit or the need for additional medication, so we do not know if SLIT reduces asthma attacks, possibly because most of the patients included in these studies had mild asthma. A few studies reported quality of life, but they used different scales, so we could not really tell if SLIT had a positive effect. Some studies reported that people taking SLIT had fewer asthma symptoms and had a reduced need for asthma medication compared with controls, but studies measured this in different ways, some of which may not be accurate. People receiving SLIT were no more or less likely to experience serious unwanted side effects, but these were generally very rare. We are not confident that this finding would apply to people with more severe asthma. People receiving SLIT were more likely to experience any unwanted side effect, but many of these were mild. Guidelines for asthma treatment suggest that SLIT should be used only for people with asthma that is difficult to control with standard treatments. However, many of the studies in this review included people with mild asthma, so trials looking at the effects of SLIT for people with more severe asthma are needed. It would be helpful if these studies used standard scales to report their findings, so that results can be combined in the future. The evidence presented in this review is generally of moderate or low quality, and very few studies have reported outcomes that are important to people with asthma, such as asthma attacks and quality of life. Most studies did not clearly explain how investigators decided which people would receive SLIT and which individuals would receive placebo or normal care, and in some studies, both participants and trial organisers knew which treatment they were getting. This may have affected the results.
As of November 2018, we found nine reviews eligible for inclusion. Seven reviews specifically investigated TENS for the treatment of pain/function in a variety of chronic conditions in adults. We also included one review investigating a range of electrotherapy modalities for neck pain and one review examining non-pharmacological interventions in people with spinal cord injury. Both of these reviews included studies investigating TENS. Though the included reviews were of high quality, we found the quality of the evidence presented within the reviews to be very low. We are unable to confidently state whether TENS is effective in relieving pain in people with chronic pain. This is due to the very low quality of the evidence, and the overall small numbers of participants included in studies in the reviews. Issues with quality, study size and lack of data meant we were unable to draw any conclusion on TENS-associated harms or side-effects or the effect of TENS on disability, health-related quality of life, use of pain-relieving medicines or people's impression of how much TENS changed their condition.
The database searches, up-to-date to February 2019, found 13 randomised controlled trials (a type of experiment in which participants are randomly assigned to one of two or more treatment groups). Three studies comprised 890 adult participants; a further 10 studies comprised 6402 infants and children. Nine studies were conducted in middle-income countries; three studies in high-income countries; and one study in a low-income country. The studies had a duration of 2 to 19 months. Three studies were supported financially by drug companies, and three studies received the vaccines from the pharmaceutical company. There is overall limited confidence in the quality of the included studies since, for example, in most trials the recipient or assessor (or both) were aware of the vaccine being given. The review included 13 studies with a total of 7292 participants (6402 children and 890 adults). Where possible, we combined the results of similar studies in a meta-analysis (a statistical method of combining the results of multiple single studies to calculate an overall effect). There are three types of wild poliovirus: types 1, 2, and 3. We found that the number of antibody responses to the vaccine (measured using something called seroconversion rates) in children was higher in the group that received the vaccine by intramuscular injection compared to the group that had a similar number of injections given intradermally, after one single dose (6 studies, 2571 children) and two doses (3 studies, 981 children) for all three types of poliovirus, and after three doses for type 2 poliovirus (3 studies, 973 children). The vaccines produce antibodies against all three types of poliovirus. The quantity of antibodies produced by the vaccines (measured as geometric median titres) was higher in children receiving a full dose of IPV via intramuscular route for all three types of poliovirus (7 studies, 4887 children). Five studies (2217 children) reported more adverse events, such as fever and redness, in the intradermal group, whilst two studies (1904 children) reported more adverse events in the intramuscular group. None of the included studies reported data on the occurrence of paralytic poliomyelitis. Based on the evidence, intramuscular full-dose IPV may result in a slight increase in seroconversion rates for all three types of wild poliovirus when compared with intradermal fractional-dose IPV. We are uncertain if a fractional dose of IPV given intradermally is better than a full dose of IPV given intramuscularly at producing antibodies for all three types of poliovirus or reducing adverse effects.
This review examined the administration-time-related effects of once-daily evening versus morning regimen on death, cardiovascular outcomes and blood pressure reduction. The interventions included chronotherapeutic delivery formulations and conventional antihypertensive agents. 21 trials, involving 1,993 patients with primary hypertension were identified. We concluded that evening dosing with antihypertensive drugs had a slightly better blood pressure control than the morning dosing regimen in 24-hour BP, but its effect on death and adverse cardiovascular outcomes is not known.
The review identified 17 randomised clinical trials. The trials reported on patient-relevant outcomes only occasionally. All trials had high risk of bias ie, a trial might systematically overestimate benefits or underestimate harms of the treatments). Both treatments were associated with a high risk of experiencing adverse events, which may lead to discontinuation of the treatment. Twelve trials reported on clearing the virus from blood six months after the end of treatment. A summary of the current evidence in this review suggests that peginterferon alpha-2a has higher chances of clearing the virus from the patient's blood than peginterferon alpha-2b (in 50% compared with 43%). We were unable to identify any evidence on the benefits of one peginterferon over the other on patient-important outcomes. There is lack of data regarding patient-important outcomes on this topic.
Randomised controlled trials (RCTs) and quasi-RCTs, comparing azithromycin to amoxycillin or amoxycillin/clavulanic acid in participants with clinical evidence of an acute LRTI, such as acute bronchitis, pneumonia and acute exacerbation of chronic bronchitis. We analysed the results from 15 trials with 2496 participants. The effects of azithromycin on cure, improvement or failure were not better than those of amoxycillin or amoxyclav. However, azithromycin seems to have a lower incidence of adverse events than amoxycillin or amoxyclav but it is not significant. Overall the quality of the evidence for the main outcome is low as only three of 15 included trials showed adequate allocation concealment. Hence, currently, there is insufficient evidence to show conclusively that azithromycin is superior to amoxycillin or amoxyclav in treating acute LRTI.
Nineteen studies met the inclusion criteria for the review, of which 16 had data on 267 participants that could be included in the analyses. The average age of people in each of the studies ranged from 56 to 76 years and 179 (67%) were men. Seven studies explored the effect of applying electrical stimulation alone and nine studies explored the effect of adding electrical stimulation to an exercise programme. Electrical stimulation was applied in a range of settings, such as at home, in an outpatient hospital department, on a hospital ward or in an intensive care unit. Most studies stimulated the thigh muscles once or twice a day for 30 to 60 minutes on four to seven days each week for four to eight weeks. Studies that explored the effect of applying electrical stimulation alone showed an increase in strength and endurance of the thigh muscles. They showed an increase in some, but not all, measures of exercise capacity and a decrease in the severity of leg fatigue after exercise. Studies that explored the effect of adding electrical stimulation to an exercise programme showed a small increase in the distance walked in six minutes. In people who were most unwell (e.g. in an intensive care unit), adding electrical stimulation to an exercise programme helped people to spend fewer days confined to bed. Electrical stimulation did not increase the risk of side effects. The quality of evidence provided by this review was low. This is because most studies had design problems. The inclusion of future studies into this review is likely to change the results.
This review looked at trials assessing the effects of topical tranexamic acid in patients who are bleeding. Twenty-nine trials were found; 28 involved patients bleeding during operations and one involved people with nosebleeds. When the results of these trials were gathered together they showed that when tranexamic acid was given topically, it reduced the amount of blood that patients lost and made it less likely that they had a blood transfusion. The authors of this review concluded that topical tranexamic acid reduces bleeding in patients who are having an operation. But because there are no trials, we are not sure if it also reduces bleeding from other causes, such as childbirth or bleeding from stomach ulcers.
Nineteen trials, of which two were newly included in this update, involving 3044 participants, were included in this review. Some trials had weak methods, which required a more cautious interpretation of their results. There were many different types of devices and methods used to place these devices for both treatments in the included trials. We found that each treatment has its own specific complications. Realigning the bones and fixing the fracture (reduction and internal fixation) is a shorter operation with less blood loss. However, people having internal fixation are more likely to need another operation than those treated with joint replacement (40% versus 11%). The reason for this is mainly from a failure of the bone to heal in those cases treated with fixation. No definite differences were found between the two treatment groups in the numbers of patients who had died by various follow-up times. People who had a replacement with an artificial hip joint that was fixed in place with cement seemed to have less residual pain and better function related to using the hip than those whose fracture was fixed. There is not enough evidence to be sure whether fixation of the bone or replacement with an artificial hip is best for treating fractures of the thigh bone near the hip joint.
Thirteen studies have rigorously evaluated 19 interventions such as services to support street-connected children and youth - all in high-income countries. Most have compared therapy-based services versus usual shelter and drop-in services, or versus other therapeutic/health interventions. We found mixed results among these studies but overall findings suggesting that participants receiving therapy and those provided usual services benefited to a similar level. Future research should consider the benefits of usual drop-in and shelter services, most particularly in low- and middle-income countries, and should focus on street-connected children and young people. None of the studies included participants comparable with street children in low-income countries, who may be on the street primarily to earn a living, or as a result of war, migration or urbanisation. Overall we assessed the quality of the evidence included in this review as low/moderate.
We found six trials (1740 participants) that used vitamin A adjunctive therapy in children with non-measles pneumonia. There was no significant reduction in mortality or duration of hospital stay. Supplementary high-dose vitamin A may result in a worsening of the disease, and low-dose vitamin A significantly reduces the recurrence of bronchopneumonia. Moderate-dose vitamin A significantly reduces the time to remission of signs in children with normal serum retinol. The possible reason of the lack of benefit of vitamin A in non-measles pneumonia is that the effects of vitamin A may be disease-specific, with vitamin A only being effective when pneumonia is complicated with measles. Further high-quality research is required.
From a wide search, we identified three RCTs that met our selection criteria. The trials involved a total of 530 adults with peripheral neuropathy. Treatments were ascorbic acid (vitamin C) in people with Charcot-Marie-Tooth disease in two trials, and amantadine in Guillain-Barré syndrome in the third. Charcot-Marie-Tooth disease is an inherited nerve disease and Guillain-Barré syndrome is a condition where there is inflammation of the peripheral nerves. We chose measures of fatigue at four to 12 weeks as our preferred measure of the effects of treatment. The amantadine trial but not the ascorbic acid trials provided data at this time point; the ascorbic acid trials provided data more than 12 months after the start of the intervention. There was insufficient evidence to determine the effects of amantadine when compared with an inactive treatment (placebo) for fatigue. and there were no major unwanted effects. We found evidence that ascorbic acid probably has little meaningful benefit for fatigue. No major unwanted effects were identified, but the trials were small. We assessed the quality of this evidence as moderate because the results were imprecise, which means they do not rule out the possibility that the drugs could have an effect. We found no evidence from RCTs on other medicines or treatments for fatigue in peripheral neuropathy. There is insufficient evidence to determine the effect of amantadine for fatigue in GBS and ascorbic acid for fatigue in CMT1A. More high-quality studies are needed to provide evidence on which to base management of feelings of fatigue in peripheral neuropathy. The cost effectiveness of different interventions should also be considered in future RCTs. The evidence in this review is current to November 2013.
The evidence is current to April 2015. This review found nine studies (1069 participants of both genders, including children, adults and older people from the USA, Japan, Belgium and Denmark) that compared various NSAIDs either with each other or with an inactive substance that has no treatment value (placebo). Our findings suggest that NSAIDs may improve most analgesia-related symptoms caused by the common cold (headache, ear pain, and muscle and joint pain), but there is no clear evidence that NSAIDs are effective in improving coughs and runny noses caused by the common cold. Some of the included trials reported gastrointestinal complaints, rash and oedema (fluid retention) in the NSAIDs group. The quality of the evidence may be estimated as 'moderate' because of imprecision. The major limitations of this review are that the results of the studies are quite diverse and the number of studies for each outcome is quite small. NSAIDs are somewhat effective in relieving the discomfort caused by a cold but there is no clear evidence of their effect in easing respiratory symptoms. The balance of benefit and harms needs to be considered when using NSAIDs for colds.
We planned to include randomised controlled trials (studies in which people or groups of people are allocated by chance to two or more groups, treating them differently). In the absence of randomised controlled trials, we planned to include studies where participants were not randomised but that included an assessment of the benefits of health education compared to no health education. We searched scientific databases and checked the titles and abstracts of 4880 possibly relevant articles and assessed the full text of 16 of these references. However, we found no studies that met our inclusion criteria. There is currently an absence of evidence to indicate whether providing health education to healthcare providers, or individuals or both, promotes early presentation and referral for women with symptoms of endometrial cancer.
Forty-five studies with a total of 3186 people are included in this review in four different comparisons: dietary advice to no advice; to oral nutritional supplements; to dietary advice plus oral nutritional supplements; and to dietary advice and nutritional supplements given together compared with no additional help. Follow-up ranged from 18 days to 24 months. There are some significant results for change in weight, muscle bulk and strength suggesting that nutritional intervention is beneficial although for some comparisons there are big differences between the studies. The authors conclude that nutritional intervention appears to be more effective than no help at improving weight, muscle bulk and strength. More research is needed to work out the best ways to help people who are losing weight because of illness in order to improve their clinical outcomes and quality of life.
We found only three trials that compared lymphadenectomy with no lymphadenectomy among women with endometrial cancer. One of these trials could not be included in the meta-analysis of this review, as it provided insufficient information about outcomes for women. When we combined findings from the two remaining trials, which included 1945 women, we found no evidence that women who received lymphadenectomy were less likely to die or have a relapse of their cancer. In addition, severe adverse events experienced as a consequence of lymphadenectomy outnumbered those reported when no lymphadenectomy was performed. The overall quality of the evidence for lymphadenectomy versus standard surgery was moderate for survival outcomes and adverse events (other than evidence for presence or absence of lymphoedema or lymphocyst, which was of high quality). The quality of evidence for quality of life was very low, as this outcome was not reported. The uncertainty of whether lymphadenectomy or no lymphadenectomy is best in the management of early-stage endometrial cancer probably reflects the fact that evidence shows no reduction in death or in disease relapse when lymphadenectomy is performed, rather than lack of evidence. In addition, women undergoing lymphadenectomy experienced more severe adverse events than those who did not undergo lymphadenectomy.
We searched the medical literature until 26 March 2015. This review includes one study with 117 participants in which a tooth (117 premolars) received a carbon fibre post, and was restored with either a fused porcelain to metal crown or a routine white filling. The study was of short duration (three years), included a relatively small number of participants, and was assessed to be at a high risk of bias due to missing results for people who dropped out of the study. The evidence produced from one study concluded that none of the 117 root-filled premolars experienced a catastrophic failure (i.e. one that cannot be repaired) after three years, although only 104 teeth were included in the final, three-year assessment. The study concluded there was no difference between treatments for the risk of non-catastrophic failure. There was no evidence available for any of our secondary outcomes: patient satisfaction and quality of life, incidence or recurrence of decay, periodontal health status, and costs. The quality of the evidence is very low. As there is only a single study, which is at high risk of bias, there is insufficient reliable evidence to determine whether single crowns are better than routine fillings. Future research should aim to provide more reliable information that can help clinicians to decide on appropriate treatment whilst taking into consideration the individual circumstances and preferences of their patients.
This review identified six randomised trials including 437 women receiving high dose chemotherapy with autograft and 413 women receiving conventional chemotherapy treatment. In the group receiving the high dose chemotherapy, there were 15 treatment-related deaths as opposed to two in the conventional chemotherapy arm. Although the high-dose treatment did not increase overall survival at 5 years compared with conventional treatment, women on the high-dose treatment survived significantly longer before experiencing recurrence of cancer. Treatment side-effects were worse in the high-dose group. On the basis of this review, the authors conclude that high dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials.
The evidence is current to November 2014. We included trials with interventions lasting at least three months. We found 11 completed trials (1369 participants). These trials showed variation in participants recruited, duration of qigong and follow-up of the interventions. For two trials that were followed up for many years after trial completion, results showed that qigong had a beneficial effect on all-cause mortality, stroke mortality and stroke incidence, but it is not clear whether this effect can be attributed to qigong, as it is uncertain whether qigong was practised during the years after the trials ended. Some beneficial effects of qigong on blood pressure and blood lipid levels were observed, but these results were based on only a small number of studies with small sample size that were at significant risk of bias. Therefore, additional large, high-quality, long-term trials are needed before we will be able to determine whether qigong is beneficial for the prevention of cardiovascular disease.
On 12 November 2015 we searched for evidence from randomised controlled trials and found a single trial conducted across four rural districts in Ghana. The trial randomised 28 community health officers (serving 2404 potentially eligible pregnant women) to the intervention group and 26 community health officers (3515 potentially eligible pregnant women) to the control group. It was uncertain from this trial whether the intervention prevented loss of more than one litre of blood (severe PPH) as the results were variable and suggested anything between a 98% decrease to a 30% increase in blood loss (very low-quality evidence). Because there were no cases of severe maternal illness (for example, because of uterine rupture), or maternal deaths, it was not possible to fully assess the effect of the intervention on those outcomes (thequality of the evidence was very low). The women receiving oxytocin had half the incidence of PPH (> 500 mL) compared with the control group (low-quality evidence). There was little or no difference between the oxytocin and control groups on the rates for transfer or referral of women to a healthcare facility (low-quality evidence), stillbirths (low-quality evidence), or the numbers of babies that died within three days of being born (low-quality evidence). There were no cases of oxytocin use during labour, needle-stick injury or any other major or minor adverse events or unanticipated harmful event. Overall, the quality of the evidence was low/very low because of methodological limitations in the trial and imprecision in the effect estimates for all the important outcomes. It is uncertain if the administration of oxytocin by community health officers without midwifery skills administered in non-health facility settings compared with a control group reduces the incidence of severe PPH, severe maternal illness or maternal deaths when compared with a control group. However, oxytocin probably decreases the incidence of PPH (> 500 mL). Considering the very specific setting where the trial was conducted and the limited role played by the community health officer in the trial, the applicability of the evidence is rather limited. Further high-quality randomised controlled trials are urgently needed to assess the effects of using oxytocin in pre-filled injection devices or other new delivery systems on severe PPH. Similarly, future studies should consider other important outcomes like possible adverse events and the acceptability of the intervention for mothers and other community stakeholders.
We found five controlled before-after (CBA) studies from South Africa, India, Uganda, and Kenya and one randomized controlled trial from the USA. The studies included over 48,000 participants. Five studies examined antiretroviral therapy and one study examined vocational interventions as a way of improving return to work in HIV+ people. The five CBA studies found that antiretroviral therapy interventions may increase employment outcomes in HIV+ people. One study assessed the effect of making changes to work tasks or the work environment but did not report enough data to say if it helped or not. We found no studies on psychological support to help HIV+ people cope better. Overall, we found very low-quality evidence because the included studies all had a high risk of bias. We found very low-quality evidence that antiretroviral therapy interventions could improve employment outcomes for HIV+ people. We need high-quality, randomized trials to find out if pharmacological, vocational, and psychological interventions can improve employment outcomes for HIV+ people.
Nine small randomised trials involving 510 adults with potentially or evidently unstable fractures, were grouped into five comparisons. The trials were too different to justify pooling of results. Only one trial used a best-practice method for preventing selection bias. Two trials comparing a bridging (of the wrist) external fixator versus pins and plaster external fixation found no statistically significant differences in function or deformity. One trial found tendencies for more serious complications but less subsequent discomfort and deformity in the fixator group. Three trials compared non-bridging versus bridging fixation, using external fixators. Two trials tested similar non-bridging fixators: one found no significant differences in functional or clinical outcomes, whereas the other found non-bridging fixation significantly improved grip strength, wrist flexion and anatomical outcome. The third trial found no significant findings in favour of multi-planar non-bridging fixation of complex fractures. One trial using a bridging external fixator found that fixing the distal fracture fragment with an extra external fixator pin gave superior functional and anatomical results. One trial found no evidence of differences in clinical outcomes for hydroxyapatite coated pins compared with standard uncoated pins. Two trials compared dynamic versus static external fixation. One trial found no significant effects from the early 'dynamism' of an external fixator. The poor quality of the other trial undermines its findings of poorer results for dynamic fixation. The review concluded that there is insufficient robust evidence to determine the relative effects of the different methods of external fixation.
Eight trials including 311 participants met the inclusion criteria for the review, of whom 306 participants were included in various comparisons. The treatments compared in five trials included necrosectomy, peritoneal lavage, and the step-up approach. Three other trials compared variations in timing of necrosectomy and methods of step-up approach. The participants in the trials had infected or sterile pancreatic necrosis resulting from varying causes. Overall, the short-term death rate (mortality over a short time) was 30% and serious adverse events (side effects or complications) rate was 139 per 100 participants. The differences in short-term mortality and percentage of people with serious adverse events were imprecise in all the comparisons. The number of serious adverse events and adverse events were fewer in the minimally invasive step-up approach compared to open necrosectomy. The complications resulting from the disease and treatment included heart failure (heart does not pump enough blood around the body at the correct pressure), lung failure (lungs do not remove waste products from the blood), kidney failure (kidneys do not remove waste products from the blood), and blood poisoning (micro-organisms and their poisons are in the blood). The percentage of people with organ failure and the average costs were lower in the minimally invasive step-up approach compared to open necrosectomy. The number of adverse events were more with the video-assisted minimally invasive step-up approach compared to the endoscopic-assisted minimally invasive step-up approach but the total numbers of procedures performed were less with the video-assisted minimally invasive step-up approach compared to the endoscopic minimally invasive step-up approach. The differences in any of the other comparisons for number of serious adverse events, percentage of people with organ failure, number of adverse events, length of hospital stay, and intensive therapy unit stay were either imprecise or were not consistent. None of the trials reported long-term mortality, infected pancreatic necrosis (in trials that included participants with sterile necrosis), health-related quality of life (which measures physical, mental, emotional, and social functioning), percentage of people with adverse events, requirement for additional invasive intervention, time to return to normal activity, and time to return to work. The overall quality of evidence was low or very low for all the measurement because the trials were at high risk of bias (e.g. prejudice of people who conducted the trial and trial participants who prefer one treatment over another) and were small trials. As a result, further studies are required on this topic.
We included 18 studies involving 2438 adults and children. Studies compared two types of steroid - prednisolone and dexamethasone - or two different doses or durations of either drug. The smallest study included just 15 people, and the largest 638. Studies followed people for between seven days and six months to see what happened to them. The evidence presented here is current to April 2016. It was difficult to combine the results of studies in a useful way because investigators used a variety of doses and durations of steroids and measured their results in different ways. Also, events such as hospital admissions and serious side effects happened very rarely in these studies, making it difficult to tell whether longer or shorter courses or higher or lower doses are better or safer, or if prednisolone is generally better or worse than dexamethasone. Some studies were old and did not use steroid doses or durations used by medical practitioners today. Any changes to the way in which asthma attacks are currently managed with oral steroids would need to be supported by larger studies than have been conducted so far. Evidence presented in this review is generally considered to be of low or very low quality, which means we are not very sure whether the results are accurate, mostly because we have not been able to combine many studies. Some studies did not clearly explain how trial organisers decided which people would receive which dose of steroids, and in some studies, both participants and trial organisers knew which dose they were getting. This may have affected study results.
We searched several electronic databases to find high quality trials about this topic. Two authors independently read reports on the trials to decide whether or not to include them in the review, and they independently extracted the trial data so as not to miss any important information. The search yielded two high quality trials including a total of 381 participants. The statistical analyses resulted in similar rates of pancreatic fistula (about 35%), deaths after surgery (about 1%) and average operation time between the two operation methods. Individual surgeons can choose which closure technique to use after removing of the tail of the pancreas according to their preferences and the participant's anatomic characteristics. More high quality trials on this topic would be beneficial, and studies investigating new methods should compare them either to stapler or hand-sewn closure in order to ensure comparability of results.
We searched the scientific literature up to May 2014 and found five relevant studies with a total of 169 participants. Participants in these studies were aged between 16 and 76 years. There were 68 females and 100 males; the gender of one participant was not reported. Two studies were conducted in China, and one each in Finland, Mexico and Turkey. All five studies compared different types of surgery or surgical devices. Thus, we found no studies comparing different types of conservative treatment or surgery versus conservative treatment. The five studies made three comparisons. We judged the evidence available for each comparison was of very low quality. This was because all the trials had design flaws that put them at high risk of bias and the studies were also too small. What the included studies found None of the studies reported on health-related quality of life, return to previous activity or cosmetic appearance. Two studies comparing biodegradable (non-metallic) versus metallic implants found little difference in outcomes (knee pain, adverse events and function) between the two groups. Neither study reported on patient-rated function. One study compared patellectomy with repositioning of a tendon with simple patellectomy (kneecap is removed) for treating complex kneecap fractures. It found that tendon repositioning resulted in more participants reporting better knee function and fewer participants with pain and limited knee function. One participant had an adverse event. Two studies found that novel methods of percutaneous fixation (surgery using small incisions to insert the fixation devices) resulted in less knee pain and fewer adverse events (mainly relating to the fracture fixation materials) than open surgery (involving wide incisions). Neither study reported on patient-rated function. Conclusions Overall, the evidence is very low quality and is insufficient to draw firm conclusions about the best method of treatment for kneecap fractures. Treatment options must be chosen on an individual patient basis, carefully considering the relative benefits and harms of each intervention and patient preferences. Further research is warranted and should be preceded by research to determine which questions should be prioritised.
We reviewed all eligible clinical trials comparing TENS to 'fake' TENS (known as 'sham'), usual care or no treatment, or comparing TENS plus usual care versus usual care alone, for neuropathic pain in adults. As of September 2016, we found 15 studies eligible for inclusion. Of these 15 studies, we were able to combine results from five studies to investigate the effect of TENS compared to sham TENS for treatment of pain. The studies involved a range of neuropathic pain problems (e.g. people with spinal cord injury, back pain with nerve involvement, complications associated with diabetes, etc.). We found the quality of the studies overall to be low. We were unable to confidently state whether TENS is effective in relieving pain compared to sham TENS in people with neuropathic pain. This is due to the very low quality of the evidence, which means we have very limited confidence in this result and that future studies are likely to change this result. Lack of reported data meant we were unable to draw any conclusion on the effect of TENS treatment on health related quality of life, pain relieving medicine use or people's impression of how TENS changed their condition. We described the results of 10 further studies comparing TENS against other types of treatment. These 10 studies were quite varied and so we could not combine them and analyse them together. This, together with the very low quality of these 10 studies, meant we were unable to judge pain relief, health related quality of life, pain medication use or impression of change. In three of the 15 studies, some people using TENS experienced skin irritation under the electrode pads. Three studies reported no problems and the remaining studies did not provide any details on side effects. Based on this, it is not realistic to comment on side effects associated with TENS use.
To assess the effects of isoflavones for the treatment of hypercholesterolaemia, we examined five randomized controlled trials of isoflavones or soy protein containing isoflavones. The trials lasted three to six months and involved 208 participants. There were no outcome data on death from any cause, cardiovascular events such as heart attack or stroke, morbidity, complications, health-related quality of life and costs. Two trials reported adverse effects, including gastrointestinal discomfort (bloating and constipation) and an increased number of hot flushes. They observed no serious adverse events. In our included studies, we found no cholesterol-lowering effect of isoflavones. However, the quality of the included trials had some considerable limitations and the number of the participants was low. Further higher-quality and rigorously performed studies on patient-important outcome measures such as cardiovascular diseases and health-related quality of life are required.
The evidence is current to December 2014. We included 18 studies. Eleven are complete, and seven are ongoing. In the completed studies, 1392 people with coronary heart disease were recruited. The average age of participants ranged from 54.9 to 66.27 years. The majority of people recruited were men. Studies were carried out worldwide, and in a variety of healthcare settings. Seven studies tested broad programmes targeting multiple lifestyle factors related to heart disease. Four studies tested programmes focused only on increasing levels of physical activity. The length of the programmes in the included studies ranged from six weeks to one year. These programmes were compared to no intervention in six studies, some support in three studies, and full traditional rehabilitation in two studies. There is no evidence to date to suggest that Internet-delivered programmes help reduce rates of death or future cardiac surgery, but this was based on a small number of studies. There is also no strong evidence to date suggesting a benefit of these programmes for lipid levels or blood pressure. There is some evidence to suggest improvements in HRQOL and behaviour change, but there is insufficient evidence to date to draw firm conclusions. Studies have not yet measured the impact of Internet-delivered programmes on medication compliance. There was very limited information on healthcare utilisation and cost of interventions. The reporting of the seven ongoing studies will add to the evidence base. The evidence was generally of low quality. The included studies were at some risk of bias, with six studies judged at high risk of bias for some risk of bias domains. The results of this review therefore need to be interpreted cautiously. There is currently limited evidence on the effects of Internet-based interventions for the treatment of coronary heart disease. We identified seven ongoing trials, which we will incorporate into this review when the results are available.
This systematic review was designed to find out whether people treated with anticoagulants soon after having a stroke got better or not, and whether they had problems with bleeding. There is a lot of information in this systematic review - 23,748 people with stroke have been involved in 24 included randomised trials to answer this question. People treated with anticoagulants did not have less long-term disability, and experienced more bleeding. Anticoagulant treated patients had less chance of developing blood clots in their legs and in their lungs following their stroke, but these benefits were offset by the increased number of bleeds. This review did not provide any evidence that the early use of anticoagulants is of overall benefit to people with strokes caused by blood clots. More research is needed to find out if there are ways to select the people with stroke who will benefit from anticoagulants without suffering the bleeding complications.
We identified 26 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups), involving 1728 opioid-dependent participants. The studies were undertaken in 12 different countries and involved treatment with an alpha2-adrenergic agonist (clonidine, lofexidine, guanfacine, and in one study, tizanidine) compared with reducing doses of methadone (12 studies), placebo (six studies), or symptomatic medications (four studies). Five studies compared different alpha2-adrenergic agonists. Treatment was scheduled to last for one to two weeks in most studies; the shortest duration was three days, and the longest was 30 days. Six studies received some financial support from a pharmaceutical company. Opioid withdrawal was similar with alpha2-adrenergic agonists and reducing doses of methadone, but the duration of treatment was longer and there were fewer adverse effects with methadone. Withdrawal signs and symptoms occurred earlier with alpha2-adrenergic agonists, within a few days of cessation of the opioid drugs. The chances of completing withdrawal treatment were similar. Clonidine and lofexidine were more effective than placebo in managing withdrawal from heroin or methadone, and were associated with higher chances of completing treatment. Lofexidine had less effect on blood pressure than clonidine. For alpha2-adrenergic agonists compared with placebo, the evidence was very low to moderate quality, indicating that further evidence would be likely to change the estimates of relative effect made in this review. However, the evidence is sufficient to indicate that alpha2-adrenergic agonists are more effective than placebo, making further comparisons of this nature inappropriate on ethical grounds. For the comparison of alpha2-adrenergic agonists with reducing doses of methadone, the evidence was low to moderate quality. The key reasons for the low quality were small numbers of studies reporting some outcomes, low rates of occurrence of some events (for example drop-out due to adverse effects), and variability between studies.
This review aimed to evaluate pure self-help (PSH) and guided self-help (GSH) interventions for eating disorders for all ages and genders, compared to psychological, pharmacological or control treatments and waiting list. Fifteen trials were identified, all focused on BN, BED or EDNOS, using manual-based self-help. There is some evidence that PSH/GSH reduce eating disorder and other symptoms in comparison to waiting list or control treatment and may produce comparable outcomes to formal therapist-delivered psychological therapies. PSH/GSH may have some utility as a first step in treatment. In the future there need to be large well-conducted effectiveness studies of self-help treatments with or without guidance incorporating cost evaluations and investigation of different types of self-help in different populations and settings.
We included 10 randomised clinical trials (studies where people are randomly put into one of two or more treatment groups) with 934 participants. All trials compared Xiao Chai Hu Tang formula with no treatment. The trials assessed different formulas and doses for three to eight months. One trial included participants with tuberculosis (a disease of the lungs that can make you cough mucous), and one trial included participants with liver cirrhosis (scarring). Only five trials with 490 participants provided data for analysis Two of the 10 included trials reported receiving academic funding. None of the remaining eight trials reported information of support or funding. None of the 10 included trials reported data on all-cause mortality (death from any cause), serious side effects (untoward medical occurrences that result in serious outcomes such as death or disability), health-related quality of life (a measure of physical, mental, emotional, and social functioning a measure of a person's satisfaction with their life and health), hepatitis B-related death, and hepatitis B-related morbidity. We are uncertain whether Xiao Chai Hu Tang formula versus no intervention has a positive or negative effect regarding side effects considered 'not to be serious', the proportion of people with detectable HBeAg (a hepatitis B viral protein that indicates active viral replication), and separately reported side effects considered 'not to be serious'. Xiao Chai Hu Tang formula compared with no intervention seems to reduce the proportion of people with detectable HBV-DNA (which is used to indicate how much hepatitis B virus is in the blood) but the reliability of this finding is low. Surrogate outcomes are markers that are used in research as a substitute for a clinically meaningful measure that directly measures patient outcomes. We cannot always be certain that such surrogate outcomes are reliable substitutes for important outcomes as they need to be officially examined. Caution is needed with this beneficial finding as the trials are at high risk of bias, and this outcome has not yet been proven relevant to patients. We identified an additional 47 studies as potential randomised clinical trials, but the data they reported were of no use. Accordingly, properly designed randomised clinical trials are needed before the benefits and harms of Xiao Chai Hu Tang formula for chronic hepatitis B can be determined. The reliability of the evidence on the use of Xiao Chai Hu Tang formula in people with chronic hepatitis B virus in terms of its beneficial or harmful effects on death, health-related quality of life, risk of dying due to hepatitis B virus infection, and serious side effects cannot be determined as no trials aimed to explore these. The reliability of the evidence that Xiao Chai Hu Tang formula, when compared with no intervention, in terms of side effects considered 'not to be serious', the proportion of people with detectable HBV-DNA, and the proportion of people with detectable HBeAg is very low. These assessments of the reliability of the evidence are due to the poor design and reporting of the included trials.
The included studies varied in the characteristics of children (e.g. age, severity of asthma), the education delivered and the way each outcome was reported. This made it difficult to compare the results and provide overall conclusions and we did not pool results for most of the outcomes. There was also diversity in the findings of the individual trials. We were able to combine the results of two studies reporting the average number of emergency department visits per child, which was not different at six months between the home education group and the group receiving the usual care. Only one trial contributed to our other primary outcome, exacerbations (flare-ups) requiring a course of oral corticosteroids. Hospital admissions also demonstrated wide variation between trials with significant changes in some trials in both directions. Quality of life improved in both education and control groups over time.
This is an update of a review previously published in February 2012. We did a new literature search up till 2 June 2014 but did not find any new studies. There are 12 studies, involving 622 participants with 648 fractures, included in this review. In all the studies we included, participants were assigned randomly to one of two groups, one group receiving treatment by ultrasound and the other group receiving no treatment or sham treatment. Most participants had a recent complete fracture of a single bone. The participants of two trials had 110 incomplete or stress fractures that resulted from heavy exercise. Four trials tested the effects of ultrasound on healing of 203 upper limb fractures and the other trials, on 130 lower limb fractures. The most commonly investigated bone was the tibia (shin bone). Eleven trials tested low-intensity pulsed ultrasound and one trial with 59 fractures tested shockwave therapy. Most trials compared a working ultrasound device with a sham device and thus protected against placebo effects. The placebo effect is a phenomenon whereby patients experience a treatment effect that is not objectively attributable to the treatment itself. However, studies varied substantially in terms of quality and risk of having biased results. In many cases the quality of reporting was poor, which made it difficult to determine which biases might have affected each study. The risk of bias across many domains therefore had to be judged as 'unclear'. The results of many trials were probably biased because of missing data from several trial participants. Additionally, the trials were very different from each other; for example, they varied in the bone that was broken and whether or not the fractures were also treated surgically. Based on analyses that adjusted for these missing data, the available evidence did not confirm that ultrasound improved the time taken for bone healing or prevented the problem of the bone failing to heal at all (eight trials with 333 fractures). The results from one low quality trial (with 59 fractures) testing shockwave therapy were inconclusive. Few complications were reported in any of the studies and these were not related to the ultrasound or shockwave therapy. While a potential benefit of ultrasound for the treatment of acute fractures in adults cannot be ruled out, the currently available evidence from 12 quite different trials is insufficient to support the routine use of ultrasound in clinical practice. Future studies should measure return to full function and normal activity and should try to ensure all participants are followed up.
Review authors working with Cochrane Oral Health carried out this review of randomised controlled trials. The evidence is current up to August 2017. We included 87 trials that investigated the success of pulp treatment of milk teeth. The trials were published between 1989 and 2017 and provided 125 comparisons of different treatment options. Pulp treatment for extensive decay in primary teeth is generally successful. The proportion of treatment failures was low, with many of the included trials having no failures with either of the treatments being compared. After a pulpotomy, mineral trioxide aggregate (MTA) seems to be the best material (in terms of biocompatibility and efficacy) to put into contact with the remaining root dental nerve. The evidence showed it to be less likely to fail than either calcium hydroxide or formocresol. After pulpectomy, it is not clear whether any medicament is superior to another. ZOE paste may give better results than Vitapex (calcium hydroxide/iodoform) paste, but more studies are needed to confirm this and to explore other treatment options. Regarding direct pulp capping, the small number of studies undertaking the same comparison limits any interpretation. Formocresol may be superior to calcium hydroxide in terms of clinical and radiological failure, but because of toxic effects associated with formocresol, safer alternatives should be evaluated. We judged the quality of the evidence suggesting the superiority of MTA over calcium hydroxide or formocresol after pulpotomy to be moderate. For other comparisons, the quality of the evidence is low or very low, which means we cannot be certain about the findings. The low quality is due to shortcomings in the methods used within the individual trials, the small number of children included in the trials and the short-term follow-up after treatment. Future trials to evaluate which healing agents are best for the three pulp treatments would require a very large sample size and should follow up the participants of a minimum of one year.
The evidence is current to September 2014. We found 26 randomised controlled trials with 2756 participants. All these trials were conducted in China with adult stroke patients of both sexes. All participants were in hospital and within the first few days after the onset of their stroke. Most trials delivered buflomedil intravenously, with a daily dose of 200 mg for 14 days. There was insufficient evidence to show whether buflomedil reduced the chance of dying or having less long-term disability in stroke survivors. Although all trials assessed outcomes immediately at the end of treatment, there was no robust evidence on the effects of buflomedil on any short-term outcomes. Also, there was insufficient evidence on the harms that the drug might cause. The quality of evidence was generally low. There were not enough data and most trials had poor study design or incomplete reporting of relevant information. To provide evidence for the use of buflomedil as a routine treatment for acute ischaemic stroke, high quality randomised trials are needed.
Twelve eligible trials with a total of 1450 mothers and 1204 known infants were included from searches, up to date as of March 2017. Eleven trials gave probiotics to mothers during pregnancy and one trial gave probiotics to mothers after the birth of their preterm infants. No studies compared maternal probiotic administration directly versus neonatal administration.The studies of pregnant women focused on various aspects of the studies with different probiotics given at different times. The pregnant women included in these trials were overall at low risk for preterm birth. The one trial with mothers given probiotics after birth was to mothers of infants who weighed less than 1500 g at birth. There is insufficient evidence to conclude whether there is appreciable benefit or harm to neonates of either oral supplementation of probiotics administered to pregnant women at low risk for preterm birth or oral supplementation of probiotics to mothers of preterm infants after birth. There were no trials that gave mothers at high risk for having a premature infant probiotics, so the effects of probiotics given to those mothers is unknown. More studies are needed to know if probiotics given to mothers of preterm infants decreases death, necrotizing enterocolitis, or other problems related to prematurity. In general, the evidence was of low to very low quality due to imprecision (small sample sizes) and indirectness (enrolled mothers were not necessarily at high risk for delivering their babies early).
Twenty-two studies (including 8641 people with COPD) compared once-daily LABA/LAMA in a single inhaler with a dummy inhaler. People were allowed to continue to use their inhaled corticosteroids (ICS) during the studies; approximately a third to a half of people were using their ICS at the beginning of each study. The evidence presented in this review is current up to December 2018. The majority of people who took part in the studies had mild-to-moderate COPD and the average age of people in each study ranged from 59 to 65 years. Six studies evaluated the once-daily combination of indacaterol/glycopyrronium, seven studies evaluated tiotropium/olodaterol, eight studies evaluated umeclidinium/vilanterol and one study evaluated aclidinium/formoterol. People who took once-daily LABA/LAMA using a single inhaler showed a greater improvement in quality of life than those taking placebo in a dummy inhaler; lung function was also improved in people taking once-daily LABA/LAMA. People taking umeclidinium/vilanterol had fewer flare-ups (exacerbations). There was no significant difference between groups (LABA/LAMA versus placebo) in the number of people who died, or in the number of people who experienced serious adverse events or any adverse event. The results were similar for the different LABA/LAMA combinations and doses that we evaluated. The included studies were generally well designed and well reported. People in the studies and those performing the research did not know which treatment people were receiving, which ensures a fair evaluation of the treatments. In three of the studies, people who were taking once-daily LABA/LAMA had more severe COPD at the start of the study than people taking dummy inhalers; this could have reduced the treatment effect seen with LABA/LAMA in these studies so we can be confident that our findings do not overestimate the effect seen with once-daily LABA/LAMA. One of the outcomes of interest (how far a person is able to walk in six minutes) was not reported by any of the included studies. Overall, we can be confident in the conclusions of this review.
We found one study with 17 people aged 10 to 41 years who had a flare up of infection with Pseudomonas aeruginosa. The people taking part were assigned to either home antibiotics or hospital antibiotics at random. Those who had home antibiotics initially spent up to four days in hospital and were taught to prepare and administer their own intravenous antibiotics. They were discharged with enough medication and equipment for the course of treatment and were visited at home. All participants received the same type of antibiotic and the course lasted at least 10 days. There were no differences found for clinical outcomes, adverse events, or complications linked to intravenous treatment. People at home were more tired and found the treatment more difficult to master. This may be due to them being more active and needing more support. Home therapy was cheaper for families and the hospital. There were no details about indirect costs. We conclude that treatment at home does not harm people in the short term and does reduce social disruption. However, the decision in favour of this option must be made on an individual basis. The evidence is very limited and more research is strongly needed to recommend its use.
We found three relevant studies, all of which were carried out in specific hospital settings. Two papers only included patients with acute stroke, and the other included those who had sustained a hip fracture. The papers differed in many other ways, so we we were unable to estimate a summary of their combined results. In general, a 'positive' IQCODE picked up patients who would go on to develop dementia (good sensitivity), but mislabelled a number who did not develop dementia (poor specificity). We cannot make recommendations for current practice, based on the studies we reviewed. The included studies demonstrated some of the challenges of research that follows people at risk of dementia over time. Not all the studies had a robust method of ensuring that none of the included participants had dementia at the start of the study, and that only new cases were identified. Similarly, many of the participants included at the start of the study were not available for re-assessment, due to death or other illness. The review was performed by a team based in research centres in the UK (Glasgow, Edinburgh, Oxford). We had no external funding specific to this study, and we have no conflicts of interest that may have influenced our assessment of the research data.
This review examined the effectiveness of interventions for oropharyngeal dysphagia in children with neurological impairment. The three studies included in the review examined oral sensorimotor treatments and lip strengthening interventions. We were interested in three primary outcomes, which were physiological functions of the oropharyngeal mechanism for swallowing (for example, lip seal maintenance), the presence of chest infection and pneumonia, and diet consistency, and three secondary outcomes, which were changes in growth, child's level of participation in the mealtime routine, and the level of parent or carer stress associated with feeding. We concluded that there is currently not enough high-quality evidence from randomised controlled trials or quasi-randomised controlled trials for any particular type of oropharyngeal dysphagia intervention in this population of children. There is a need for larger-scale randomised controlled trials to evaluate the effects of interventions for oropharyngeal dysphagia in children with neurological impairment.
This review included three studies involving 1257 birthing women. The findings showed that placental cord drainage in the management of third stage of labour reduced the length of third stage of labour by a mean of about three minutes and reduced blood loss by average of 77 ml. There was no clear difference in the manual removal of placenta or the risk of postpartum haemorrhage or incidence of blood transfusion. The trials did not report on maternal pain or discomfort during the third stage of labour. Some of the outcomes were not reported in the same way in all trials, limiting the amount of information available for analysis. Other desired outcomes were either not reported or were not reported in an appropriate way for statistical analysis (e.g. placenta not delivered within 30 minutes after birth, maternal haemoglobin changes). Further investigation of the effect of placental cord drainage on maternal outcomes would be useful although it is not a priority area for maternity research.
There is insufficient evidence from randomised controlled trials to evaluate the effectiveness of sustained-release naltrexone. In the one controlled study that met inclusion criteria, 60 outpatients were randomised to one of three groups that received two sequential depot injections of naltrexone (192 or 384 mg) or placebo injections. The mean dropout time was 48 days with high dose naltrexone compared with 27 days on placebo; an increase in  treatment of 21 days (range 11 to 31 days). The lower depot dose gave a lesser benefit. The number retained in treatment at eight weeks did not show a clear difference and ranged from a mean of 68% to 39% of participants in  the different groups. 'Wanting heroin' did not differ on naltrexone but 'needing heroin' scored significantly lower with depot naltrexone compared to placebo. The most prominent adverse effects were general symptoms of  fatigue and pain at the injection site. Seventeen reports met inclusion criteria for assessing adverse effects. Seven looked specifically at naltrexone implants for treatment of opioid dependence and wound infection, allergic reaction to the implant and number of implants removed. The majority of the trials did not have a control group and systematic assessment of adverse effects was lacking.
We searched electronic databases and identified randomized controlled trials (in which participants are randomly allocated to one of two or more treatment groups) consisting of participants who received high-pressure oxygen therapy or room air or no treatment as a control. The evidence is current up to December 2015. We found a single, small study of 60 children that evaluated high-pressure oxygen therapy for ASD. There was no evidence that high-pressure oxygen therapy improved social interaction, behavioral problems, speech or language communication, or mental function in children with ASD. However, children who received high-pressure (hyperbaric) oxygen therapy showed an increased occurrence of ear barotrauma events when compared with those in the control group. The quality of the evidence is low. Evidence is insufficient to confirm that high-pressure oxygen is an effective treatment for individuals with ASD.
Subsequent trials, however, failed to confirm these findings and also failed to show a substantial benefit for community-wide presumptive treatment for STIs. This is likely due to the endemic nature of HIV and relatively low incidence of STIs in these populations. There are, however, other good reasons as to why STI treatment services should be strengthened and the available evidence suggests that when an intervention is applied and accepted in a community, it can improve the quality of services provided. The trial in Masaka District, Uganda showed an increase in the use of condoms, a marker for less risky sexual behaviours, although a newer study by Gregson conducted in Zimbabwe suggested no effect. With the last three trials having shown disappointing results with respect to HIV prevention, it is unlikely that further community trials will be conducted, let alone yield different results. Future trials of biomedical interventions that involve individual randomisation, however, may represent an opportunity to reexamine presumptive treatment of STIs. Such trials should also aim to measure a range of factors that include health-seeking behaviour and quality of treatment, as well as HIV, STI and other biological endpoints.
We searched for Cochrane reviews that analysed the data from randomised controlled trials (RCT; experiments that randomly allocate participants to one of two or more treatment groups), which looked at the effectiveness of CR in adults with heart disease and compared patient outcomes with a no-exercise control group. This overview summarised the findings from these reviews. We found six high-quality Cochrane reviews that included 148 RCTs in 98,093 people who primarily had experienced a heart attack, had undergone cardiac surgery or had chronic heart failure. The findings of this overview showed important benefits of CR participation that included a reduction in the risk of hospital admissions, as well as improvements in health-related quality of life compared with not undertaking rehabilitation. The quality of the RCTs in the included systematic reviews was variable, and limitations in their methodological quality led to downgrading of the quality of the evidence, which varied widely by review and outcome. We make the following recommendations for the future conduct and reporting of systematic reviews of CR. • The scope of CR reviews needs to reflect current guidelines that recommend that CR should be based on an individually prescribed programme of exercise training with appropriate co-interventions. • Future CR reviews need to explore the complexity of CR using appropriate approaches to explore the association between intervention characteristics and outcomes across trials. • Future Cochrane CR reviews need to standardise their methods and reporting.
This review of two small trials suggests that nasal intermittent positive pressure ventilation (NIPPV) delivered via nasal prongs may be more effective than NCPAP alone in preterm babies whose apneas are frequent or severe. Further research is needed to confirm effectiveness and safety as few babies have been studied so far.
This review compared these treatments and found both were equally effective at preventing death but using stents was better than balloon angioplasty because fewer arteries needed to be re-cleared and stents prevented more heart attacks than balloon angioplasty.
Our review included randomized controlled trials that compared the incidence of shunt infection in patients who were given preventive antibiotic therapy with those who did not receive these drugs. We also included trials comparing antibiotic-impregnated shunt systems with those who received non-antibiotic impregnated shunts. We included seventeen trials in our review. Although the available data does not provide much detail on mortality or the adverse events caused by antibiotics (an adverse event is an incident in which harm resulted to a person receiving the health care) it does support the use of preventative systemic prophylactic antibiotics for the first 24 hours postoperatively following an intracranial ventricular shunt operation or the use of antibiotic-impregnated catheters. However this data was obtained from an intermediary outcome which is the rate of shunt infections. Therefore although the evidence suggests that the use of antibiotics is beneficial in reducing the incidence of shunt infection more research is needed to confirm their benefit.
We searched scientific databases and found two randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) including 86 adults that met our inclusion criteria. Both trials compared implantable cardioverter defibrillators with medical therapy in people with Brugada syndrome who had already survived a sudden cardiac arrest event. We found no studies in people who had not experienced such an event or with other abnormalities. These two studies were small, were performed by the same investigators from Thailand, were funded by a device company, and had major methodological limitations, including being stopped early. Nearly all (98%) participants were men who had an average age of 44 years old. All-cause mortality (death from any cause) was lower in people who received the implantable cardioverter defibrillator. Rates of survived sudden cardiac arrest, heart attack, and stroke were higher, primarily due to differences in survived sudden cardiac arrest rates. Implantable cardioverter defibrillators had a higher rate of side effects compared with medical therapy, including receiving inappropriate shocks from their defibrillators, which required reprogramming of these devices. There was low quality evidence that implantable cardioverter defibrillators lower mortality in people with inherited heart rate abnormalities who have survived a sudden cardiac arrest event because of few, small, low quality studies. These devices carry a higher risk of side effects than medical therapy. Further research is very likely to have an important impact on our confidence in the results.
The quality of evidence for the outcomes recurrent blood clots and death was moderate. The quality of this evidence was downgraded because of the small number of events reported, leading to imprecision. For the outcome bleeding, the quality of evidence was low because of inconsistency between studies and risk of bias. Continued research into long term treatment of blood clots in the veins with LMWH and VKA is needed. This review found no clear differences in recurrent blood clots and death between LMWH and VKA, and fewer bleeding episodes with LMWH than with VKA. However, when only high-quality studies were compared for bleeding, no clear differences were observed between LMWH and VKA. LMWH may offer an alternative for some patients, for example, those in geographically inaccessible areas, those unable or reluctant to visit the thrombosis service regularly, and those for whom taking VKA may be harmful.
The review results are based on 17 controlled trials that randomised a total of 1103 people with acute DVT (within 21 days of onset of symptoms) to receive thrombolysis or anticoagulant treatment. Trials were carried out principally in the USA, Scandinavia, Germany and the UK. All trials included men and women ranging in age from 18 to 75 years with a preponderance of older adults. The present review (current until February 2016) showed that thrombolysis may have advantages over standard anticoagulation treatment. Thrombolysis effectively dissolved the clot so that complete clot breakdown occurred more often with thrombolysis than with standard anticoagulant therapy. Blood flow in the affected vein (venous patency) was also better maintained. Three trials (306 participants) continued for over six months and found that fewer people developed PTS when treated with thrombolysis, 45% compared with 66% in the standard anticoagulation treatment group. Two trials (211 participants) which continued for over five years also showed that fewer people developed PTS when treated with thrombolysis. Those receiving thrombolysis had more bleeding complications than with standard anticoagulation (10% versus 8%). Most bleeding episodes and deaths occurred in the older studies. Use of strict eligibility criteria appears to have improved the safety of this treatment, which is effective delivered directly to the clot by catheter or via bloodstream from another vein. Qualitity of the evidence Using GRADE assessment, the evidence was judged to be of moderate quality due to many trials having low numbers of participants. However, the results across studies were consistent and we have reasonable confidence in these results.
We searched for all relevant randomised controlled trials up to 23 August 2016. We identified two trials involving 80 participants. One compared early versus delayed open appendicectomy in 40 children and adults with appendiceal phlegmon. The other trial compared early versus delayed keyhole (laparoscopic) appendicectomy (where surgery is performed through a very small incision) in 40 children with appendiceal abscess. Studies took place in the USA and India. The age of the individuals in the trials varied between 1 year and 84 years, and 27.5% were females. Both two studies were small and had a number of limitations so we cannot be certain about how the effects of the two surgical approaches compare. From one trial in children and adults comparing open with delayed appendicectomy, there was insufficient evidence to show the effect of using either approach on the overall complication rate or the proportion of participants who developed wound infection. Our certainty in a longer stay in hospital stay and time away from normal activities with open appendicectomy is very low. There were no deaths in the study. Quality of life, and pain were not reported in this trial. The other trial in children with appendiceal abscess receiving either early or delayed keyhole appendicectomy did not report on overall complication rates. The trial did not provide enough evidence to show the effect of using either approach on the length of hospital stay among participants. We have very low certainty that children who had early keyhole appendicectomy had better quality of life compared with children who had delayed keyhole appendicectomy. The study did not report if there were any deaths, and did not provide information on pain, or time away from normal activities. At present the benefits and harms of early versus delayed appendicectomy are not well understood because the current information is based upon very low quality evidence. Both trials were at a high risk of bias. Overall, we judged the quality of the evidence to be very low. Thus, further well-designed trials are urgently needed.
We included 15 trials in this review that assessed whether massage could help reduce neck pain and improve function. Results showed that massage is safe, and any side effects were temporary and benign. However, massage did not show a significant advantage over other comparison groups. Massage was compared with no treatment, hot packs, active range-of-movement exercises, acupuncture, exercises, sham laser, manual traction, mobilization, and education. There were a number of challenges with this review. Overall, the quality of the studies was poor and the number of participants in most trials was small. Most studies lacked a clear definition, description, or rationale for the massage technique used. Details on the credentials or experience of the person giving the massage were often missing. There was such a range of massage techniques and comparison treatments in the studies that we could not combine the results to get an overall picture of the effectiveness of massage. Therefore, no firm conclusions could be drawn and the effectiveness of massage for improving neck pain and function remains unclear.
We searched for studies up to 2 February 2015. We identified two trials with a total of 2343 participants. The trials were conducted in the USA and France and investigated the use of fish oil supplements in people with AMD who were at high risk of progressing to advanced disease. We judged the studies to be at low risk of bias. One study was funded by government grants and the other study was funded by the manufacturer of the dietary supplement. These studies found that omega 3 supplementation for periods up to five years did not reduce the rate of progression to advanced AMD or reduce significant visual loss compared to a placebo. The incidence of adverse effects was similar in the intervention and placebo groups. We judged the quality of the evidence on rate of progression to AMD to be high, and the quality of the evidence for other outcomes to be moderate because the estimates were imprecise.
In this review involving 1010 adults and children with asthma, we found that tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide (compared to clinical symptoms with or without spirometry/peak flow) was beneficial in reducing the final (but not the overall) daily inhaled corticosteroid doses in adults. However in children inhaled corticosteroid dose was increased when exhaled nitric oxide guided strategy was used. There was no difference between groups in other asthma outcomes (exacerbations, spirometry, FeNO or symptom control). Thus tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide cannot be routinely advocated.
We identified five studies, with a total of 749 participants enrolled and 565 participants providing data, which addressed the research question and met the inclusion criteria. They all compared saline irrigation with routine care or other nose sprays. These studies covered a wide range of ages, countries, sample sizes, dosing methods and frequency, and time since onset of URTI symptoms. They were also highly variable in their design and the symptoms that were measured. This is not surprising due to the lack of consistent measures of URTI symptoms and signs. This resulted in very few common outcome measures that could be combined across these five studies. The evidence is current to August 2014. The two additional studies included since the original systematic review have not contributed data of sufficient size or quality to materially change the original findings. Only the largest study, which studied 401 children aged 6 to 10 years, found significant reductions in a number of symptoms, including nasal secretions, sore throat, nasal breathing score and nasal obstruction, as well as reduced use of additional nasal decongestant medications. It also reported a significant improvement in the health status score. There was a reduction in the outcome of time to resolution of symptoms, which was reported in two trials on adult participants, but the difference was not clinically significant. Nasal saline is safe but may cause minor adverse effects, such as irritation or a burning sensation, particularly with products using higher flows or concentrations. Most studies were small and had significant shortcomings in the design or implementation of the research. Further studies, preferably larger in size and using common outcome measures, are needed to establish the potential for the role of nasal saline irrigation in reducing the severity and duration of acute URTI symptoms, secondary infections and possibly antibiotic usage.
The three studies included in our review provide very limited evidence of the effectiveness of methadone for chronic non-cancer pain. We were unable to combine results statistically, and there were too few participants in each study to be confident in their results. No conclusions can be made regarding differences in effectiveness or side effects between methadone and placebo, other opioids, or other treatments.
We identified six clinical trials that met our standards for inclusion in the review. They included a total of 1319 participants. We decided that our main measure of whether antiviral medicines work in preventing PHN would be whether or not PHN had developed six months after a first attack of shingles (some of the studies we included of aciclovir measured PHN at four months). Aciclovir, which is an antiviral medicine, was used in five trials (900 participants) and was not better than a placebo (dummy pill) in preventing PHN. In the other trial (419 participants), famciclovir, which is another antiviral drug, was no better than placebo in preventing pain following healing of the shingles rash. The number of side effects with aciclovir and famciclovir was not very different from the number with placebo. The trials did not have any major problems of design or conduct that put the results in doubt, although most of the reports did not provide enough information to fully assess every aspect. We conclude that according to high quality evidence, oral aciclovir was ineffective in reducing the incidence of PHN and there is not enough evidence on other antiviral treatments. There need to be further well-designed trials of famciclovir or other new antiviral agents with a greater number of participants. Future trials should pay more attention to the severity of pain and quality of life of participants, and should include different groups of people, such as those who have lowered immunity. The evidence is current to April 2013, when the searches were last updated. Because new evidence on this topic is slow to emerge, we have scheduled the next update of this review for 2017.
We identified three randomised controlled trials (RCTs), which are studies that randomly assign participants into different treatment groups, that looked at whether adding focused (targeted) radiation (radiosurgery) to WBRT is beneficial to people with brain metastases. Overall, participants who underwent WBRT and SRS did not survive longer than participants who were treated with WBRT alone. However, participants with high functional status to perform activities of daily life and those with a single metastasis did survive longer after SRS and WBRT. Participants treated with WBRT and SRS did experience improved local control and performance status, as well as decreased steroid use compared to participants treated with WBRT alone. The overall quality of the evidence was moderate based on the GRADE assessments for our outcomes of interest, and the overall risk of bias was unclear. Most of our conclusions are based on the results of one large trial with unclear risk of bias and therefore, we cautiously make the following remarks: we found that when radiosurgery was added to WBRT, there was no evidence to suggest that people lived any longer than if they had WBRT alone, except for people with only one brain metastasis (who may live longer if they receive the combination treatment). People having combination treatment also seemed to function better in daily life, their treated tumors were associated with having less chance of growing back, and they had to take less steroid medication. The side effects of combined therapy and WBRT alone were similar.
We identified 56 relevant trials, involving 3105 participants, up to March 2017. Twenty-six studies (1410 participants) compared treadmill training with body weight support to another physiotherapy treatment; 20 studies (889 participants) compared treadmill training without body weight support to other physiotherapy treatment, no treatment, or sham treatment; two studies (100 participants) compared treadmill training with body weight support to treadmill training without body weight support; and four studies (147 participants) did not state whether they used body weight support or not. The average age of the participants was 60 years, and the studies were carried out in both inpatient and outpatient settings. The results of this review were partly inconclusive. People after stroke who receive treadmill training with or without body weight support are not more likely to improve their ability to walk independently. The quality of this evidence was low. However, treadmill training with or without body weight support may improve walking speed and walking capacity compared with people not receiving treadmill training. The quality of this evidence was moderate. More specifically, people after stroke who are able to walk at the start of therapy appear to benefit most from this type of intervention, but people who are not able to walk independently at therapy onset do not benefit. This review found that improvements in walking speed and endurance in people who can walk have no lasting positive effect. Unwanted events such as falls and dropouts were not more common in people receiving treadmill training. Further analysis showed that treadmill training in the first three months after stroke produces only modest improvements in walking speed and endurance. For people treated at a later stage (more than six months after their stroke) the effects were smaller. More frequent treadmill training (for example, five times per week) appears to produce greater effects on walking speed and endurance; however, this was not conclusive. Brief periods of treadmill training (duration of four weeks) provided a modest improvement in walking speed but not enough to be clinically important. Effects of the age of participants or the type of stroke were not investigated in this review. In practice, it appears that people who can walk after stroke, but not those who cannot, may profit from treadmill training (with and without body weight support) to improve their walking abilities. Further research should specifically investigate the effects of different frequencies, durations or intensities (in terms of speed increments and inclination) of treadmill training, as well as the use of handrails. Future trials should include people who can already walk, but not dependent walkers who are unable to walk unaided. Future research should analyse age groups, gender, and type of stroke to see who might benefit most from this treatment. The quality of evidence for treadmill training for walking after stroke was low to moderate. It was moderate for walking speed and walking endurance at the end of treatment and low for improving the ability to walk independently.
We conducted a literature review up to March 2017 and three studies were included according to our selection criteria. The three studies reported data on 110 participants. All three studies investigated whether introducing probiotics directly into the bladder to create a non-harmful colony will prevent urinary tract infections in people with bladder dysfunction, predominantly people with spinal cord injury. Two studies reported that this method was generally safe. This review found that generally, the studies were poor quality with high risk of bias. We found the effectiveness of colonisation with probiotics in preventing bladder infection in people with bladder dysfunction is uncertain. Furthermore, the success of colonisation was variable, and the colonisation process is invasive and demands a high level of commitment on the part of the participant. We did not identify any studies investigating whether other probiotics and other administration routes is effective in preventing urinary tract infections in people with bladder dysfunction. It is uncertain if probiotics prevent urine infections in people with bladder dysfunction after a nervous system injury. Further robustly designed studies are necessary.
In this review we included 142 studies with more than 1.1 million participants looking for an association between green tea consumption and cancers of the digestive tract and the female reproductive system, breast, prostate, kidney and urinary tract, nasopharynx, lung, blood, skin, thyroid and brain. The majority of the studies were of medium to high quality in terms of how they were conducted. Overall, the evidence from the studies showed that the consumption of green tea consumption to reduce the risk of cancer was inconsistent. Some studies suggested a beneficial effect on cancer risk, while others indicated no effect, and even suggested a slightly increased cancer risk. In particular, results from experimental studies suggested that green tea extract supplementation yielded a decreased risk for prostate cancer, but increased risk for gynaecological cancers. For non-melanoma skin cancer no difference in cancer cases emerged. Green tea supplementation seemed to slightly improve quality of life compared with placebo, although it was associated with some adverse effects including gastrointestinal disorders, higher levels of liver enzymes, and, more rarely, insomnia, raised blood pressure and skin reactions. In nonexperimental studies, comparing people consuming the highest amount of green tea to those in the lowest category of consumption, we found an indication of a lower occurrence of new cases of overall types of cancer, while no difference emerged for lethal cases. However, results according to the type of cancer and study design were inconsistent. A beneficial effect of green tea consumption on cancer prevention remains unproven so far. Caution is advised regarding supplementation with high-dose green tea extracts due to the possible adverse effects.
We identified 22 new studies, so the evidence in this review update now rests on 52 studies with 3731 participants. The findings suggest that music therapy and music medicine interventions may have a beneficial effect on anxiety, pain, fatigue, heart rate, respiratory rate and blood pressure in people with cancer. Because of the very low quality of the evidence for depression, it is unclear what impact music interventions may have. Music therapy but not music medicine interventions may improve patients' quality of life. We did not find evidence that music interventions improve mood, distress or physical functioning, but only a few trials studied these outcomes. We could not draw any conclusions about the effect of music interventions on immunologic functioning, coping, resilience or communication outcomes because there were not enough trials looking at these aspects. Therefore, more research is needed. No adverse effects of music interventions were reported. Most trials were at high risk of bias, so these results need to be interpreted with caution. We did not identify any conflicts of interests in the included studies. We conclude that music interventions may have beneficial effects on anxiety, pain, fatigue and quality of life (QoL) in people with cancer. Furthermore, music may have a small positive effect on heart rate, respiratory rate and blood pressure. Reduction of anxiety, fatigue and pain are important outcomes for people with cancer, as they have an impact on health and overall QoL. Therefore, we recommend considering the inclusion of music therapy and music medicine interventions in psychosocial cancer care.
The evidence is current to July 2015. In this update, we identified seven randomised controlled trials that compared only giving platelet transfusions to treat bleeding versus giving platelet transfusions to prevent and treat bleeding . One trial is still recruiting participants and has not been completed. We reviewed six randomised controlled trials with a total of 1195 participants. These trials were conducted between 1978 and 2013. Five of the trials included adults who were receiving chemotherapy or a stem cell transplantation as treatment for blood cancers. One of the trials included children receiving chemotherapy for leukaemia. Four of the six studies reported funding sources; these were charitable foundations or government funds. Giving platelet transfusions to prevent and treat bleeding in patients with low platelet counts due to blood cancers or their treatments may result in a reduction in bleeding when compared with giving platelet transfusions only to treat bleeding. There may not be an increased risk of death or adverse events if platelet transfusions are only given to treat bleeding versus giving platelet transfusions to prevent and treat bleeding, but there was not enough evidence to be certain about this. Giving platelet transfusions only when bleeding occurs probably reduces the number of platelets given. None of the six studies reported any quality-of-life outcomes. The evidence for most of the findings was of low or moderate quality, as patients and their doctors knew which study arm the patient had been put in; outcomes reported in the studies were difficult to compare because bleeding was measured and reported differently; and some outcomes were imprecise, because the outcome did not happen very often (such as death).
Previous studies have suggested that decreasing blood glucose levels to within a low, narrow range (strict control) around the time of surgery may decrease infections and improve outcome. However, concerns about side effects from low glucose levels, such as seizures and increased risk of death, have prevented widespread use of this strategy. There are only five trials comparing strict control strategies with the conventional strategy of treating blood glucose levels only when they become high. These trials differ significantly in patient characteristics, glucose targets, medications and methods used to lower glucose levels, as well as the outcomes measured. Furthermore, the individual studies, which are small and/or flawed, do not demonstrate a significant decrease in surgical site infections. There are insufficient data to support the routine adoption of strict blood glucose control around the time of operation to prevent surgical site infections.
We found six randomised controlled trials comparing a gradient, swim-up or wash technique, in a total of 485 couples undergoing IUI. The evidence is current to March 2019. We are uncertain whether there is a difference in pregnancy outcomes between the three sperm preparation techniques for subfertile couples undergoing IUI. No studies reported on live birth rates. Considering the quality of evidence (very low), we are uncertain whether there was a difference between clinical pregnancy rates (CPR) for swim-up versus a gradient technique. The results suggest that if the chance of pregnancy after the use of a gradient technique is assumed to be 24%, the chance of pregnancy after using the swim-up technique is between 14% and 30%. We are uncertain whether there was a difference between ongoing pregnancy rates per couple, multiple pregnancy rates (MPR) per couple or miscarriage rates (MR) per couple when comparing a swim-up versus gradient technique. The quality of the evidence for these outcomes was very low. No studies reported on ectopic pregnancy rate, fetal abnormalities or infection rate. Considering the quality of evidence (very low), we are uncertain whether there is a difference in clinical pregnancy rates after a swim-up technique versus wash and centrifugation. The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 38%, the chance of pregnancy after using the swim-up technique is between 9% and 41%. Considering the very low-quality evidence, we are uncertain whether there was a difference between multiple pregnancy rates between swim-up technique versus wash technique. Miscarriage rate was only reported by one study: no miscarriages were reported in either treatment arm. No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate. Considering the quality of evidence (very low), we are uncertain whether there is a difference in clinical pregnancy rates after a gradient versus wash and centrifugation technique. The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 13%, the chance of pregnancy after using the gradient technique is between 8% and 46%. Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates per couple between the treatment groups. Considering the quality of evidence, we are also uncertain whether there was a difference between miscarriage rates per couple between the treatment groups. No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate. The quality of the evidence was very low. The main limitations were (unclear) risk of bias, signs of imprecision (small number of studies/participants included) and inconsistency in results among studies.
We included 21 studies involving 1,690 caregivers caring for persons with a range of diagnosed conditions. Caregiver ages ranged from 19 years to 87 years. Most were female and caring for a family member. The majority were spouses, in particular wives, except for one study that mainly focused on adult children. Most caregivers had greater than secondary school education. Eighteen studies reported funding from reputable sources. Key results Nineteen studies (18 studies contributing data) compared telephone support interventions and usual care. Telephone support interventions probably have little or no effect on caregiver quality of life (4 studies, 364 caregivers) and may have little effect on burden (9 studies, 788 caregivers) compared to usual care on completion of the intervention. Although anxiety may be slightly reduced and preparedness to care slightly improved following the intervention, we are uncertain about the effects on depression and overall, telephone interventions may have little or no effect on the outcomes assessed by this review. High satisfaction with the intervention was reported in six studies that measured this outcome, but no comparative data from usual care groups was reported. Two studies compared telephone and non-telephone-based support interventions. There may be little or no evidence of an effect of telephone support when compared non-telephone-based support interventions for any reported outcome. No adverse events were measured or reported in any of the included studies. Quality of evidence The quality of the evidence was assessed as very low to moderate across outcomes, thus reducing confidence in the findings. Many of the results were based on data from single studies with few participants. Larger well-designed studies are required to determine the effects of telephone support interventions.
Therefore, we conducted a systematic review assessing the influence of CSFs on disease and infection-related outcomes. Our review showed that the addition of CSFs to chemotherapy in AML patients affected neither overall survival, nor the achievement of disease remission or the rate of relapse. Importantly, they did not affect the rate of infections in this population. We concluded that CSFs post-chemotherapy should not be given routinely in AML patients. However, their administration could be considered on an individual basis.
This review included 15 trials, of a moderate risk of bias, that involved over 4600 women and their babies. In this review, TRH, given with corticosteroids to women at risk of early birth, was not shown to further reduce the breathing difficulties for the babies. Babies born to mothers who had received TRH with corticosteroids, were more likely to require support for breathing than babies born to mothers who received only corticosteroids. Women receiving TRH were more likely to experience adverse side effects, such as nausea, vomiting and flushing than women who only received corticosteroids. Therefore, based on the current available evidence, TRH is not recommended to be given to women at risk of preterm birth for preventing neonatal respiratory disease.
In this Cochrane review, the review authors compared children given intermittent anti-TB treatment to those given daily treatment. They examined the evidence up to 30 May 2013 and included four randomized trials that compared twice-weekly treatment with daily doses of anti-TB drugs, but none evaluated thrice-weekly dosing. The four trials included 563 children aged five months to 15 years, not known to be resistant to TB drugs. The trials were published over 12 years ago and the regimens used are not those currently recommended. The trials were small, and did not detect a difference between twice-weekly or daily treatment in the number of children who were cured, died, relapsed, reported taking most or all of the drugs, or had adverse effects. Whether regimens of drugs two or three times a week are as good as regimens with daily doses remains unclear, as the evidence base to date is small, and the regimens tested are not the same as currently currently recommended drug combinations.
This study undertook a comprehensive search of the literature unrestricted by country of publication or language. Unfortunately small numbers of relevant trials were found and these were of variable quality. This review found that although anticholinergic drugs are well tolerated, in children over two years of age, there is not enough data to be sure if they are better than placebo in terms of effects on lung function or symptoms.
50 studies with 7793 participants were included in the review, in most studies treatment was provided over a period of three months. The review shows that more patients who took naltrexone were able to reduce the amount and frequency of drinking than those who took an identical appearing, but inert substance (placebo). On average, one out of nine patients was helped by naltrexone. Naltrexone does not have serious side effects, but gastrointestinal symptoms like nausea, stomach pain and loss of appetite are common. Some patients also get tired from naltrexone. For injectable formulations of naltrexone, which can be advantageous for patients who have problems with taking their medication on schedule, and the second opioid antagonist nalmefene, the database is still too sparse to allow final conclusions. Nevertheless, the available studies indicate that these drugs might have comparable effects on drinking than oral naltrexone has. Naltrexone does not cause dependency and unlike disulfiram, another medicine that is sometimes used to treat alcohol dependence, it does not make patients feel sick if they drink alcohol while taking it.
. A search for relevant randomised studies was conducted in January 2013. The review includes three studies with 80 participants. All participants had tardive dyskinesia as a result of taking antipsychotic medication and were randomised into treatment groups. One group received pyridoxal 5 phosphate, the other group received a placebo. Antipsychotic treatment continued as usual throughout the trials. . People taking pyridoxal 5 phosphate in these studies experienced more than 40% improvement in their tardive dyskinesia compared to those on placebo, so had less severe tardive dyskinesia. Experience of side effects were similar between treatment groups with participants taking pyridoxal 5 phosphate experiencing no more or less side effects than participants in the placebo group and they did not experience greater worsening of their psychiatric symptoms than those on placebo. Evidence from the studies is weak, but suggests pyridoxal 5 phosphate may be effective in the treatment of tardive dyskinesia. . Evidence is weak. The number of studies and participants is few. The quality of studies is low. Better evidence could be gathered by better designed, conducted and reported trials. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/.
Method: We reviewed randomised controlled trials investigating the efficacy of any of the drugs commonly used to treat cognitive impairment after TBI. We included only studies which started treatment at least 12 months after the injury; by this time the cognitive impairment is usually stable. Results: We identified only four trials for inclusion. These investigated four different drugs—modafinil; the experimental drug (−)-OSU6162; atomoxetine; and rivastigmine—against placebo. On most measures there was no difference between treatment and placebo. Furthermore, the quality of the evidence was assessed as very low. The experimental drug called (−)-OSU6162 was better than placebo on three cognitive measures, although this was a small study with only six participants with TBI. Modafinil, atomoxetine and rivastigmine were not found to be better than placebo. No difference between modafinil and placebo was found on assessment of clinical global improvement. Compared to placebo, more participants on modafinil and fewer on rivastigmine dropped out of the trials. More people taking modafinil, atomoxetine and rivastigmine experienced adverse effects than those on placebo, although the difference is most likely due to chance. Only nausea was statistically more likely in those taking rivastigmine. In the study of (−)-OSU6162, one participant of three given placebo experienced adverse effects requiring a dose reduction, with no drop-outs reported. No studies reported any deaths. Conclusion: Recommendations for, or against, drug treatment of chronic cognitive impairment in TBI cannot be made on the basis of current evidence.
The review authors searched the medical literature and identified two randomised controlled trials with a total of 134 hospitalized neonates and older children who had tetanus from Nigeria (19 neonates, seven children aged between one month and 10 years of age) and Indonesia (74 neonates, 34 children aged between three days and 12 years). All drugs were given orally as medications and feeds are usually given via nasogastric tube in the settings where the disease burden is high. Neither study provided information on the safety of the interventions or followed up survivors beyond discharge from hospital.
It was not possible to extract the results from the first phases of two included crossover studies of D-cycloserine for Alzheimer's disease and therefore the meta-analyses are based on the included two parallel group 6-month studies. The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.
This review compares effectiveness and side effects of adenosine and CCAs in terminating SVT episodes. We included in the review seven trials involving 622 patients. Evidence is current to July 2017. Combined analysis of these trials showed no differences between adenosine and CCAs in successfully treating SVT. This finding is based on moderate-quality evidence. A temporary drop in blood pressure that did not require treatment was reported in only one of 152 study participants treated with CCAs, and low-quality evidence suggests that no patients treated with adenosine experienced low blood pressure. We have no data on length of stay in hospital nor on patient satisfaction. Moderate-quality evidence shows no differences in effects of adenosine and calcium channel antagonists for treatment of SVT on reverting to sinus rhythm, and low-quality evidence suggests no differences in cases of hypotension. None of these trials examined patient preferences, which is an important factor in deciding which drug is the 'best' treatment.
We searched for randomised clinical trials recruiting participants presenting with biliary colic and comparing NSAIDs versus no intervention, placebo, or other drugs. We included 12 randomised clinical trials with 828 participants, of whom 416 received NSAIDs and 412 received placebo, spasmolytic drugs, or opioids, in the review. Considering the common occurrence of biliary colic, these numbers of trials and participants are insufficient. Elderly participants and participants with co-morbidities were poorly represented in the trials. Twenty-four per cent of the participants were males. The age of participants ranged from 18 to 86 years. All people were admitted to emergency department for acute biliary pain. There was no mortality. None of the included trials reported quality of life. We found that NSAIDs significantly reduced biliary pain when compared with placebo and spasmolytic drugs. NSAIDs also significantly reduced cholelithiasis-related complications (e.g. acute cholecystitis, acute pancreatitis, jaundice, cholangitis) as compared to placebo and spasmolytic drugs. One trial comparing NSAIDs versus opioids reported results on complications, finding no significant difference between treatments. None of the trials reported major adverse events. Seven out of 12 trials reported minor adverse events; in two out of the eight trials adverse events were not observed, and minor events were reported in the remaining five trials. We found one ongoing randomised clinical trial aimed at assessing the analgesic effectiveness of intravenous ibuprofen in biliary colic. The trials appeared to be free of industry sponsorship or other type of for-profit support that may manipulate the trial design, conductance, results, or conclusions of the trial. The quality of evidence according to GRADE criteria (a system developed to grade evidence and recommendations in health care) was moderate for the comparison NSAIDs versus placebo for the outcome lack of pain relief and low or very low for the other outcomes and comparisons. Only one of 12 trials was at low risk of bias following predefined 'Risk of bias' domains. The results of the present systematic review with meta-analysis suggest that NSAIDs can be used for pain relief, but further randomised clinical trials are warranted, and NSAIDs should be used with care in certain patient groups, such as the elderly and people with co-morbidities.
We reviewed the evidence on how effective indirect laryngoscopy, or videolaryngoscopy, is when compared with direct laryngoscopy for intubation in children from 28 days to 18 years old. We found 12 randomized controlled trials (803 children) that met our inclusion criteria. The evidence is current to November 2015. We reran the search in January 2017 and will include the three studies awaiting classification when we update the review. For intubation, use of indirect laryngoscopy, or videolaryngoscopy, took longer and was more likely to be unsuccessful (very low-quality evidence). No significant difference was found between direct and indirect laryngoscopy when success of the first attempt at intubation was assessed (low-quality evidence). Only a few studies reported the effect of intubation on adverse haemodynamic response, including changes in oxygen saturation, heart rate, and trauma to the mouth and windpipe. Therefore, it was difficult to conclude on the overall adverse effect (very low-quality evidence). Indirect laryngoscopy might provide better views of the vocal cords. We found considerable variation in results from included studies in terms of assessment of intubation time, number of attempts at intubation, number of unsuccessful intubations, adverse effects, and assessments of how well the vocal cords were seen. None of the included studies was funded by a laryngoscope manufacturer, hence minimizing the risk of other bias. The quality of the studies varied, and only a few were of highest quality. For these reasons, we graded the overall quality of evidence as very low.
We included only studies consisting of women with breast cancer who had completed active cancer treatment. These studies compared outcomes of women involved in PA interventions versus outcomes of those who were offered usual care or no PA. Participants must have been assigned to a group in random or somewhat random fashion. The evidence is current to September 2015. This review includes 63 trials involving 5761 participants. Most trials (28) consisted of aerobic exercise (e.g. walking, cycling, dance), whereas seven trials included a resistance training-only group, and 21 trials included a combined aerobic exercise and resistance training group. One in five participants placed in a PA intervention group dropped out before the end of the study, and on average one-quarter of target PA sessions were missed by participants. We found no studies that looked at effects of PA after cancer treatment on risk of recurrence or dying from breast cancer or any other cause. We found that participants performing PA had more favourable values by the end of the intervention and experienced greater positive changes over the intervention period in terms of QoL, views on their emotional health and physical ability, social function, feelings of worry, stamina, PA levels, body fat, and strength of muscles, compared with usual care participants. Researchers found no effects on perceived health, ability to sleep, feelings of pain, sexual function, body mass index, waist-to-hip girth ratio, and bone health of the upper and lower spine or hip. At least three months after completion of the intervention, actual values and changes from the start of the intervention in feelings of tiredness, stamina, and self-reported PA levels remained more favourable in participants given PA intervention than in those given usual care. Both aerobic exercise only and combined aerobic and resistance training interventions improved QoL and stamina. Aerobic exercise improved views on perceived emotional health and physical ability, as well as social function and self-reported PA levels, whereas resistance training resulted in greater improvement in muscle strength. Combined aerobic and resistance training interventions led to reduced feelings of tiredness. Trialists reported few minor adverse events among those given PA interventions. We rated the quality of evidence related to various aspects of health as very low, low, or moderate. We noted wide variation among the interventions that we looked at in terms of types of PA, frequency of sessions per week, levels of effort among participants, and session and intervention duration. Also, researchers measured aspects of health in many different ways. Other problems with eligible studies included lack of information on how study authors placed participants in groups at random, whether researchers who were carrying out the tests knew which group the person being tested belonged to, and how researchers dealt with data missing from their studies. In many aspects, we could not rule out the chance that positive effects observed were small enough that they were not important. It is also possible that smaller studies that have not found favourable effects of PA in women with breast cancer after treatment have not been published, because study authors often find it difficult to publish studies that have not found beneficial effects.
This review compares the survival of women with advanced epithelial ovarian cancer, who had IDS performed between cycles of chemotherapy after primary surgery, with survival of women who had conventional treatment (primary debulking surgery and adjuvant chemotherapy). It found similar survival rates in women who did and did not receive IDS. Not enough information about adverse effects was available. Information on quality of life of the women was also inconclusive.
This review assessed the effects of providing selenium supplements to healthy adults in order to prevent the occurrence of cardiovascular disease. Whether selenium supplements would reduce the risk factors associated with heart disease was also examined. We found 12 trials in which 19,715 healthy adults were randomly assigned to receive selenium supplements or placebo. The vast majority of participants involved in these trials were male individuals from the US, where people are already well nourished and take large amounts of selenium from natural foods. Overall, the included studies were regarded as at low risk of bias. In our review, providing selenium supplements to healthy adults did not prevent the occurrence of major cardiovascular disease. The increased risk of developing type 2 diabetes when taking selenium supplements, as suggested in some previous studies, could not definitely be ruled out in our review. In summary, this review of the available evidence to date suggests that taking selenium supplements is neither beneficial nor harmful for cardiovascular disease, but it is probably unnecessary for those who are already well nourished and who take large amounts of selenium from natural foods.
The review includes one study with 40 children with cystic fibrosis aged between seven and 17 years of age. This study compared a specially designed singing intervention with other non-physical leisure activities (recreation) and children were selected for the singing or the recreation program randomly. The study lasted two weeks and children were followed up for between six and eight weeks. The study assessed the impact of singing on respiratory muscle strength, quality of life and lung function tests. Participants from both the singing and recreation groups reported some improvement in quality of life measurements. Participants in the singing group showed a greater increase in maximal expiratory pressure (a substitute measure of respiratory muscle strength test), while there was no improvement in this outcome for those in the recreation group. No adverse events were reported. There is currently not enough evidence to assess the effect of singing on clinical outcomes in people with cystic fibrosis. Future studies using robust methods are needed to assess the possible effects of singing for people with cystic fibrosis The included study was limited by the small number of participants (only 51 participants enrolled and only 40 were analysed) and a high drop-out rate (21%). We also think the fact that the young people who were enrolled in the study were keen to sing, could have affected the study results.
We identified 15 studies enrolling 352 patients with only one study enrolling both men and women. Studies evaluated the effects of phosphodiesterase-5 inhibitors (PDE5i), zinc, vitamin E, vitamin D or bromocriptine compared to placebo. In two studies (101 patients) PDE5i significantly increased the individual domains and the overall International Index of Erectile Function-5 (IIEF-5) score and the complete 15-item IIEF tool (1 study, 41 patients). End of treatment testosterone levels were not significantly increased by addition of zinc to dialysate (2 studies, 22 patients) but oral zinc improved end of treatment testosterone levels (1 study, 20 patients). There was no difference in plasma luteinizing and follicle-stimulating hormone levels at the end of the study period with zinc therapy. Little data were available for vitamin E, bromocriptine and dihydroxycholecalciferol in CKD patients and there were no studies of intracavernous injections, transurethral injections, mechanical devices or behavioural therapy in people with CKD. PDE5i and zinc are promising interventions for treating sexual dysfunction in men with CKD however evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for both male and female sexual dysfunction in CKD, considering the significant disease burden.
The results of clinical studies that have been undertaken to study the effect on the outcomes of IVF and ICSI procedures of culturing embryos under low oxygen concentrations have been conflicting. Therefore, we performed a systematic review and meta-analysis of the literature to find the best available evidence. It has shown that culturing embryos under low oxygen concentrations does indeed improve clinical outcomes after IVF and ICSI, such as number of deliveries (live birth rate) and ongoing and clinical pregnancy rates. Furthermore, no evidence was found of an increased risk of adverse events such as multiple pregnancies, miscarriages and congenital abnormalities. We concluded that culturing embryos under low oxygen concentrations seems beneficial with an increase in the number of newborns, but more studies are needed to strongly prove this effect.
It has been used for physiological studies and it has also been proposed as a treatment for depression. Sixteen trials were included in the review and fourteen contained data in a suitable form for quantitative analysis. Most comparisons did not show differences between repetitive (rTMS) and other interventions. No difference was seen between rTMS and sham TMS using the Beck Depression Inventory or the Hamilton Depression Rating Scale, except for one time period (after two weeks of treatment) for left dorsolateral prefrontal cortex and high frequency; and also for right dorsolateral prefrontal cortex and low frequency, both in favour of rTMS and both using the Hamilton scale. Comparison of rTMS (left dorsolateral prefrontal cortex and high frequency) with electroconvulsive therapy showed no difference except for psychotic patients after two weeks treatment, using the Hamilton scale, which indicated that electroconvulsive therapy was more effective than rTMS.
This review of interventions for PD-associated peritonitis identified 42 studies (2433 participants). Many studies were small, out-dated, of poor quality, and had inconsistent definitions and dosing regimens. In general, information about the best treatment of peritonitis in people on PD may be insufficient to guide therapy. We found that intraperitoneal antibiotics appear to improve treatment responses compared with IV antibiotics. Glycopeptides may increase likelihood of cure compared with first generation cephalosporins. There appears to be no certain role for routine peritoneal lavage (washing) or use of clot-breaking (fibrinolytic) agents. New and larger randomised controlled trials that compare the effects of IV versus intraperitoneal antibiotics and different antibiotic types on patient-relevant outcomes including adequate assessment of treatment harms are still needed.
The review authors investigated 281 studies that claimed to be randomised controlled trials and that used Chinese herbal medicines in the treatment of ectopic pregnancy.Only two of these studies were confirmed to be randomised controlled trials. Both trials were of poor quality in terms of design and how they were conducted.These studies did not provide clear evidence that CHM is beneficial in the treatment of ectopic pregnancy.
This review includes evidence up to 11 August 2015. We included eight randomised controlled trials with a total of 474 participants. All of the patients were adults who had chronic rhinosinusitis with nasal polyps. All of the studies followed patients until the end of treatment (two to three weeks) and three studies (210 participants) followed up people for three to six months after the initial treatment had ended. Five of the eight reports mentioned how the trial was funded. None of the funding sources were pharmaceutical companies. At the end of a two- or three-week treatment course, people who took oral steroids may have had a better quality of life, less severe symptoms and smaller nasal polyps than people who had placebo or did not receive any treatment. After three to six months, there was little or no difference in quality of life, symptom severity or nasal polyps between the people who had oral steroids and the people who had placebo or no intervention. The people who took oral steroids may have had more gastrointestinal disturbances and insomnia than the people who had placebo or no intervention. It is not clear if the people who took oral steroids had more mood disturbances than the people who had placebo or no intervention. We judged the quality of the evidence for oral steroids plus intranasal steroids for adults with nasal polyps to be low (further research is very likely to have an important impact on our confidence in the effect estimate and is likely to change the estimate), as the some of the results are only from one or two studies, which do not have a lot of participants. Most of the trials do not have a high risk of bias, but only people with nasal polyps were included in the review.
Searching for studies up to May 2014, we found two high quality trials involving 2193 participants that tested beta-blockers after stroke in people with a recent stroke or TIA. No clear evidence indicated that beta-blockers reduced the risk of stroke, heart attack, or death from vascular disease. Participants who received beta blockers instead of placebo showed significantly more adverse effects. More studies with larger samples are needed.
This review of four trials found insufficient evidence to conclude whether supportive devices prevent subluxation or not and found no evidence to conclude whether supportive devices can reposition the head of humerus in the glenoid fossa of an already subluxed shoulder.
Studies have shown that musculoskeletal disorders are the most common cause of sick-leave and disability in many industrial countries. Neck pain is more common in the general population than previously known.This Cochrane review presents what we know from research about the effect of workplace interventions for workers with neck pain who, for the most part, are not sick-listed. Ten trials with 2745 participants were included in this review. Two studies were rated as having low risk of bias. The workplace interventions comprised education about stress management, principles of ergonomics, anatomy, musculoskeletal disorders, and the importance of physical activity. They taught 'pause gymnastics', how to use a relaxed work posture, proper positioning, the importance of rest breaks, and strategies to improve relaxation. Some studies also included how to modify work tasks, work load, working techniques, working positions, and working hours. Several studies suggested how to make adjustments and recommended alternatives to the existing furniture and equipment at the workplace. The present review found low quality evidence that those who received workplace interventions did not get more pain relief than those who received no interventions. We found moderate quality evidence (1 trial, 415 workers) that workplace interventions reduced sick leave among the workers at six month-, but not at three- and 12-month follow-ups. This could be due to the fact that few participants in the study were sick-listed. Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate for both pain and sickness absence.
Studies have shown that stroke survivors and their carers often report they have not been given enough information about stroke and feel unprepared for life after discharge from hospital. However, the best way to provide information after stroke is unclear. The authors of this review looked at the evidence for the effectiveness of providing information to patients, or carers of patients, who have had a stroke or transient ischaemic attack (TIA), sometimes called a mini-stroke. They examined randomised trials (studies) in which one group of stroke patients or carers who were given the intervention being tested (such as a course of lectures) was compared with a group of stroke patients or carers who received standard care. Twenty-one studies, involving 2289 patients and 1290 carers, are now included in this updated review. Overall, the studies showed that providing information to patients and carers improved their knowledge of stroke and increased patient satisfaction with some, but not all, of the information they received about stroke. There was also an effect on reducing patient depression, although the reduction was small and may not be enough to seem meaningful to patients. When information was provided in a way that more actively involved patients and carers, for example by offering repeated opportunities to ask questions, it had more effect on patient mood than information which was given on one occasion only. There is not much evidence that providing information had effects on other aspects of patient or carer stroke recovery such as independence or social activities.
Working with Cochrane Oral Health, we searched for studies that had been published up to November 2016. We found three studies that focused on the prevention of MRONJ and two studies that tested treatments for MRONJ. The studies involved 1218 adults, with the smallest study having 40 participants and the largest study having 700 participants. Most study participants were women, but one study was of men with prostate cancer receiving bisphosphonate infusions (given by drip into a vein). All studies included only participants treated with bisphosphonates (used to support treatment and reduce risk of fracture and bone pain), although several other drugs are also known to induce MRONJ. One study provided low-quality evidence that dental examinations at three-month intervals and preventive treatments (antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) are more effective than standard care for reducing the number of cases with MRONJ in a group of people receiving intravenous bisphosphonates for cancer-related conditions. In the experimental group (which received preventive care consisting of antibiotics and specific wound closure), fewer people developed MRONJ (2 participants per 100 who underwent close monitoring) compared with the control group (23 participants per 100 who had standard care). There was insufficient evidence to conclude that the use of the other interventions investigated would reduce the risk of MRONJ or would improve healing of MRONJ. The quality of evidence was low or very low. This was due to limitations in how the studies were designed and run. For example, some participants changed groups during the study, some participants did not finish the study, and the outcomes were measured at different follow-up times.
We searched scientific databases for clinical trials comparing baclofen with placebo (a pretend treatment) or another potentially useful medicine in people with AWS. We included four randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 189 participants. One study from the USA compared baclofen to placebo given over at least 72 hours. The 31 participants were mainly men with the average age 47 years. Two studies with 85 participants compared baclofen to diazepam (a calming medicine) for 10 consecutive days, or for 10-day inpatient stay with flexibility to allow negotiation of the discharge date between day 10 and day 15. One study compared baclofen to chlordiazepoxide given for nine days, in which the 60 participants were all men with an average age of 38 years. None of studies reported any conflict of interest. Addolorato 2006 was supported by Associazione Ricerca in Medicina, Italy. Girish 2016 was supported by KIMS Hospital and Research Centre (Bangalore, India). Jhanwar 2014 reported no funding source. Lyon 2011 was supported by Duluth Clinic Foundation (MN, USA). None of the included studies assess the main outcomes of the review, that is, alcohol withdrawal seizures (fits), alcohol withdrawal delirium (confused thinking and awareness), and craving. We are uncertain whether baclofen improves withdrawal symptoms and signs, and reduces side effects when compared with placebo or other medicines as the quality of the evidence was very low. The quality of the evidence from the studies was very low and results should be interpreted with caution. In the future, well-designed, double-blind (where neither the participant nor the researcher knows which treatment has been given until after the results have been collected) RCTs with large numbers of participants are required to test how effective and well tolerated baclofen is in people with AWS.
We searched for evidence on 30 May 2016. We identified six randomised controlled trials involving a total of 636 women and 1298 babies. The women were at 17 to 33 weeks pregnant when they entered the trials. The overall risk of bias of the trials was low and the evidence in general was of low quality. Advising women with a multiple pregnancy to either continuously rest in bed (five trials, 495 women and 1016 babies) or rest in bed for several hours during the day but with some physical activity allowed (one trial, 141 women and 282 babies) in hospital did not reduce the risk of very preterm birth (birth before 34 weeks of gestation), infant deaths before or up to one week after the birth or, low birthweight babies (strict bed rest only) compared with women who maintained daily activities at home. Women receiving strict bed rest in hospital were more likely to go into labour normally (four trials, 488 women) and had babies with a higher mean birthweight (three trials, 314 women) compared with women without activity restrictions at home. Partial bed rest in hospital reduced the number of pregnant women developing high blood pressure (one trial, 141 women, low-quality evidence) but the same benefit was not observed with strict bed rest (five trials, 495 women). Adverse effects such as the development of venous thromboembolism or mental, emotional, social and spiritual well-being (psychosocial) effects, and women’s views and experiences of bed rest were not reported in the included trials. Neither were the costs of the intervention reported on. We did not find sufficient evidence to support or refute bed rest for women with a multiple pregnancy as a way of preventing preterm birth and other pregnancy complications.
Overall, evidence was low- or very low-quality. This means we have limited or little confidence in the results, and that it is possible that other similar research could find something different. The main reasons for this assessment were that there were few studies that included few people, and a risk that results were not fully reported. All included studies had problems recruiting enough participants, making it more difficult for them to detect effects of stopping antipsychotics. Limited evidence suggests that stopping long-term antipsychotic drug use in older people with dementia and NPS may be done without making their behaviour worse. There may be benefits especially for those with milder NPS. There may be people with more severe symptoms who benefit from continuing treatment, but more research in people with both milder and more severe NPS is needed to be sure about this. The overall conclusions have not changed since the last version of this review and the number of included trials is still low.
We searched the scientific literature to identify randomised controlled trials (RCTs) of interventions designed to improve informed consent in clinical practice.  We wanted to determine primarily whether these interventions improved all components of ‘informed consent’ (understanding, deliberation and communication of decision).  Other individual outcomes of direct relevance to patients (e.g. recall/knowledge, understanding, satisfaction and anxiety), those related to healthcare professionals (e.g. ease of use of intervention, satisfaction) and system outcomes (e.g. cost, rates of procedural uptake) were also assessed. We included 65 studies involving a total of 9021 patients.  The studies varied according to the type of intervention, the procedure for which consent was sought, the clinical setting and the outcomes measured.  Most interventions were written or audio-visual.  Only one study assessed all the elements of informed consent, but the design was not robust; all other studies assessed only components of informed consent.  When the results of multiple studies were combined, we found that interventions improved knowledge of the planned procedure, immediately (up to 24 hours), in the short term (1 to 14 days) and the long term (more than 14 days).  Satisfaction with decision making was increased; decisional conflict was reduced; and consultation length may be increased. There were no differences between the intervention and control for the outcomes of generalised anxiety, and either anxiety or satisfaction associated with the consent process. Limitations of the review include difficulties combining the results of studies due to variation in the procedures undergone by patients, the interventions used and outcomes measured.  This means that we are uncertain as to which specific interventions are most effective but pragmatic steps to improve information delivery and consideration of the information are likely to benefit patients.
The evidence is up to date as of June 2016. We found 37 studies involving a total of 4129 people. Most of the people in the studies were aged over 65. There was a mix of new and experienced hearing aid users. Seven studies funded by the United States Veterans Association dominate the evidence. The 1297 people in these studies were serving in the military or military veterans. All but two of the other studies included fewer than 100 people in each study. Thirty-three of the 37 studies looked at ways to help someone to manage their hearing loss and hearing aid(s) better by giving information, practice and experience at listening/communicating or by asking people to practise tasks at home. These are forms of self-management support. Most of these studies also changed how the self-management support was provided, for example by changing the number of appointment sessions or using telephone or email follow-up. Six studies looked at the effect of just changing how the service was delivered. No studies looked at the effect of using guidelines or standards, computerised medical record systems, community resources or changing the health system. We found no evidence that the interventions helped people to wear their hearing aids for more hours per day over the short, medium or long term. One study that used interactive videos to give information after hearing aid fitting encouraged more people to wear their hearing aids. We found no evidence of adverse effects of any of the interventions, but it was rare for studies to look for adverse effects. Giving self-management support meant that people reported less hearing handicap and improved verbal communication over the short term. When this was combined with changing how the support was delivered people also reported slightly more hearing aid benefit over the long term. Only six studies (287 people) looked at how people were doing after a year or more. Complex interventions that deliver self-management support in different ways improve some outcomes for some people with hearing loss who use hearing aids. We found no interventions that increased self-reported daily hours of hearing aid use. Few studies measured how many people use hearing aids compared to how many are fitted (adherence). Many things that might increase daily hours of hearing aid use or encourage more people to wear the hearing aids they have been fitted with have not been tested. It was difficult to combine data across different studies because many outcome measures were used and results were not always fully reported. In future it would be helpful if researchers: - used existing guidelines for presenting their results; - agreed a set of outcome measures for use in this type of study; and - focused on long-term outcomes where people are followed up for at least a year. We judged the evidence to be of very low or low quality. There was risk of bias in the way many of the studies were carried out or reported. The largest studies included only military veterans. We do not know whether studies would find the same results in more mixed populations. Most of the other studies had small sample sizes. Very few studies measured long-term outcomes.
We searched the literature for robust evaluations of the effectiveness of organisational interventions in promoting EBP in nursing. We included one study from the USA which involved one hospital and for which the number of nurses was not reported. The study evaluated the effects of a standardised evidence-based nursing procedure on improved nursing care for patients at risk of developing healthcare-acquired pressure ulcers (HAPUs), as measured by the HAPU rate. If a patient's admission Braden score was lower than or equal to 18, nurses were authorised to initiate a prevention pressure ulcer care bundle, without a physician order. The Braden scale is a tool used to assess a patient's risk of developing pressure ulcers. An adult with a score below or equal to 18 is considered to have a high risk for developing a pressure ulcer. Re-analysis of the HAPU data, as an interrupted time series, was suggestive of a trend in rates prior to intervention and, if that trend was assumed to be real, there was no evidence of an intervention effect at three months (mean rate per quarter 0.7%; 95% confidence interval (CI) 1.7 to 3.3; P = 0.457). Given the small percentages post intervention it was not statistically possible to extrapolate effects beyond three months. Considering the importance placed on organisational change in promoting EBP in nursing, it is surprising that eight years after the previous empty Cochrane review was published, appropriately evaluated organisational infrastructure interventions are still lacking. If policy-makers and healthcare organisations wish to promote evidence-based nursing at an organisational level successfully, they must ensure the funding and conduct of well-designed studies to generate evidence to guide policy.
We identified 13 eligible studies (2794 participants) for this review. One trial did not report any information that we sought. Information on 213 participants was not reported because of various reasons, the common reason being that they did not receive the planned treatment. A total of 2528 participants received either laparoscopic gastrectomy (1288 participants) or open gastrectomy (1240 participants). The decision on whether a participant received laparoscopic or open gastrectomy was made using methods similar to the toss of a coin. This process ensures that the participants in the two groups are similar. All the participants were suitable for major surgery. There was no difference between laparoscopic and open gastrectomy in short-term deaths (laparoscopic gastrectomy: 6 deaths in 1000 operations versus open gastrectomy: 3 deaths in 1000 operations). There is a certain amount of uncertainty when predicting the number of deaths or outcomes based on information in the trials. Because of this uncertainty, we were able to conclude that there was no difference in short-term deaths between the groups, although the deaths in laparoscopic gastrectomy was twice that in open gastrectomy. None of the trials reported health-related quality of life, time to return to normal activity or time to return to work. The differences in long-term deaths, serious complications within three months (laparoscopic gastrectomy: 36 complications per 1000 operations versus open gastrectomy: 60 complications per 1000 operations), all complications within three months (laparoscopic gastrectomy: 161 complications per 1000 operations versus open gastrectomy: 253 complications in 1000 operations, short-term and long-term recurrence of cancer, number of people who required blood transfusion, amount of blood transfused during or within one week of surgery, and length of hospital stay were imprecise. As a result, significant benefits or harms of laparoscopic gastrectomy compared to open gastrectomy cannot be ruled out. Further well designed trials are necessary to compare the benefits and harms of laparoscopic and open gastrectomy. The quality of evidence was very low for all outcomes, apart from short-term mortality, which was low. As a result, there is a lot of uncertainty regarding the results.
All included trials randomised participants with acute respiratory infections to receive antibiotics based on procalcitonin levels ('procalcitonin-guided' group) or a control group. The trials were performed in primary care, the emergency department and medical wards, and the intensive care unit. Included participants had acute upper or lower respiratory infections, including pneumonia, bronchitis, exacerbation of chronic obstructive pulmonary disease, and others. All studies were investigator-initiated trials. Half of the trials were funded by national agencies or did not report funding, and half of the trials received funding from the biomarker industry (e.g. Thermo Fisher Scientific). We studied 6708 participants from 26 trials in 12 countries. Mortality at 30 days was significantly lower in procalcitonin-guided participants compared to control participants (286 deaths in 3336 procalcitonin-guided participants (8.6%) versus 336 deaths in 3372 controls (10.0%)). There was no significant difference with regard to treatment failures. Results were similar for different clinical settings (primary care, emergency department, intensive care unit) and types of respiratory infection. Regarding antibiotic exposure, participants in the procalcitonin-guided group had a 2.4-day reduction in antibiotic exposure and a reduction in antibiotic-related side effects (16.3% versus 22.1%). The quality of the evidence was high for mortality and antibiotic exposure. Most of the trials did not use blinding, however we did not expect that mortality would be biased by this limitation. The quality of the evidence was moderate for treatment failure and antibiotic-related side effects because the definitions for these endpoints among trials were not identical.
This is an update of an earlier review. The evidence is current to September 2015. We only identified one new study with 2305 participants. In total, we analysed four randomised controlled studies with 4187 participants. The comparison of warfarin with aspirin was based on a large number of patients from four high-quality studies. The analysis showed an almost identical risk of death with both drugs. There was not enough evidence to prove benefits of warfarin over aspirin to reduce the possibility of clotting complications, such as a heart attack or stroke. However, patients receiving warfarin experienced serious bleeding twice as often as those taking aspirin. A comparison of warfarin with another antiplatelet drug, clopidogrel, was based on a single medium size study, and it showed similar results: no difference in occurrence of death or clotting complications, but a higher chance of developing of a serious bleed. There is currently no evidence to suggest advantages of warfarin over antiplatelet drugs in heart failure with a normal rhythm. Moreover, treatment with warfarin leads to more bleeding events than aspirin or clopidogrel. It is unlikely that further studies will change these conclusions unless new, more effective and safe drugs become available.
We collected and analysed all relevant studies to answer this question (date of search: November 2017). Our updated review included 40 studies which provided data on 4884 babies and their mothers. Studies were undertaken across the world, but mostly in high-income countries. Births were in hospitals which practiced early clamping. For many outcomes there were insufficient data to be really confident of our findings. 1) For delayed cord clamping (with immediate care of the baby after cord clamping) compared with early cord clamping, we found it likely that fewer babies died before discharge (20 studies, 2680 babies). Also, fewer babies may have had any bleeding in the brain (15 studies, 2333 babies), but there was probably no difference in the numbers of babies with very serious brain bleeds (10 studies, 2058 babies). 2) Only one study of 276 babies and their mothers provided data on delayed cord clamping with immediate care of the baby beside the mother with cord intact compared with early cord clamping. This study was small and did not identify any marked differences in health outcomes. 3) For delayed cord clamping (with immediate care of the baby after cord clamping) versus cord milking, there were insufficient data (three studies, 322 babies) to make comparisons between outcomes. 4) For cord milking versus early cord clamping, we found 11 studies providing data with 1183 babies and their mothers. Again, there were insufficient data to make clear comparisons on outcomes. Delayed cord clamping probably reduced the risk of death for babies born preterm. Early cord clamping probably causes harm. No studies showed what length of delay was best, and only a few studies followed babies for health outcomes in early childhood. There is insufficient evidence for reliable conclusions on providing immediate care for the baby beside the mother with the cord intact. Similarly, there is insufficient evidence for reliable conclusions on cord milking. Further studies are in progress.
This review found three small trials in adult haemodialysis patients (n = 117). The evidence for the benefits and risks of correcting metabolic acidosis is very limited with no RCTs in pre-ESRD patients and none in children. These trials suggest there may be some beneficial effects on both protein and bone metabolism but the trials were underpowered to provide strong evidence.
We identified eight trials that used different types of chemotherapy (e.g. platinum agents, doxorubicin, topotecan or paclitaxel) but there was not sufficient evidence to prove any of the drugs were better than observation alone. An important consideration for women with advanced disease is the balance between the benefit of treatment and the harms or adverse effects that these treatments may cause. There were insufficient data to comment on the overall impact of the maintenance chemotherapy on clinical benefit from the women's perspective. We tried to identify all trials and both published and unpublished data in this review; thereby minimising the influence of publication bias. The included trials are graded as moderate quality but this meta-analysis currently provides a reliable assessment of the average treatment effect of platinum and doxorubicin among women with advanced epithelial ovarian cancer. Use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy has not proved effective to prolong the life time of women with epithelial ovarian cancer. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required.
In populations of children living in endemic areas, the effect of the first, single dose of deworming drugs on weight is unclear. There was little or no effect in most studies, except for a large effect detected from one study area in Kenya, reported in two trials carried out over 30 years ago in a school where children were heavily infected with worms. This causes uncertainty, which means we do not know if a first dose or single dose of deworming impacts on weight. For height, most studies showed little or no effect, with the exception of the site in Kenya. A single dose of deworming medicine probably has no effect on haemoglobin and cognition. There is insufficient data to know if there is an effect on school attendance, school performance, or physical fitness or mortality. In studies where children were regularly treated with deworming medicine there was little or no effect on weight in all but two trials, irrespective of whether children were heavily infected with worms or not. The two trials with large average weight gains included the Kenya study carried out over 30 years ago, and one study from India carried out over 20 years ago in a low worm burden area where later studies in the same area did not show an effect. In trials from 2000 onwards, which are more relevant given the global reduction in worm burden, there is little or no effect. This causes uncertainty and means we do not know if regularly treating children with deworming medicine improves their weight. Regularly deworming children probably has no effect on height, haemoglobin, cognition, and mortality. We do not know if there is an impact on school attendance, since the evidence is inconsistent and at high risk of bias. There is insufficient data to know if there is an effect on physical fitness. Authors' conclusions For public health programmes to regularly treat all children in endemic areas with deworming drugs, there is quite substantial evidence of no benefit in terms of haemoglobin, cognition, school performance, and mortality. For weight, contemporary studies do not show an effect, but unusually large effects were seen in studies over 20 years ago.
This review includes two trials, involving a total of 80 adults with simple elbow dislocations that had been put back into place (reduced). Both trials were at risk of bias, which means that their results may not be reliable. One trial compared early mobilisation of the elbow with immobilisation for three weeks in a plaster cast. This trial found no firm evidence of differences between the two interventions in the recovery of elbow range of motion or pain at one year. None of the trial participants had an unstable elbow or had suffered another dislocation. The other trial compared surgical repair of the torn ligaments versus conservative treatment (cast immobilisation for two weeks). It found no significant difference between the two groups in the numbers of patients who considered their injured elbow to be inferior to their non-injured elbow or in other patient complaints about their elbow such as weakness, pain or weather-related discomfort. There were also no differences between the groups in the range of motion of the elbow or grip strength at follow-up of around two years. There were two people with surgery-related complications. None of the trial participants had an unstable elbow or had suffered another dislocation. Overall, the review concluded that there was not enough evidence from randomised controlled trials to show which methods of treatment are better for these injuries.
This review on the effects of Padma 28 includes five trials with a total of 365 participants (current until September 2015). The review showed that Padma 28 has some beneficial effects in improving maximum and pain-free walking distance. The groups treated with placebo did not show an improved maximum and pain-free walking distance. Unfortunately the studies reported insufficient data to allow the comparison of the change in walking distances in the Padma 28 group with the change in walking distances in the placebo group. Combining the data of maximum walking distance after treatment in two studies showed that there was a longer maximum walking distance in the Padma 28 group compared with the placebo group after 16 weeks of treatment. No change in ankle brachial pressure was observed. Mild side effects such as gastrointestinal discomfort, tiredness and skin eruption were also noted but these were not different between the Padma 28 and placebo groups. Quality of the evidence Overall, the quality of the studies was low, with evidence of publication bias, small number of trials, limited reporting of the analyses that compared treatment groups and bias due to a high percentage of withdrawals in the placebo groups because of lack of improvement or deterioration of the overall condition. We therefore feel there is currently insufficient evidence to draw conclusions about the effectiveness of Padma 28 in the routine management of IC. Further well-designed research would be required to determine the true effects of this herbal preparation.
. The Cochrane Oral Health Group carried out this review and the evidence on which it is based was up-to-date on 2 January 2014. We included 14 studies, which took place from 1990 to 2009 in the UK, Egypt, Saudi Arabia, and the USA. These included 1152 participants aged from 2 to 40 years. Although the 14 studies included addressed our research question, they differed in the way that they delivered the intervention and what they measured. This meant we could not combine their data in our analyses. The results from individual studies for pain, bleeding, and other adverse effects were uncertain. The use of additional different painkillers may have hidden the effect of the LA. Further high-quality trials are needed in order to assess the benefits or harms of LA given to children and young people whilst they are receiving dental treatment under GA. Issues that these trials need to address include local side-effects (e.g., excessive dribbling and accidental lip biting), side-effects on other parts of the body (e.g., the heart), participant and parent satisfaction, dosage, type of anaesthetic, and the effects of extra painkillers (e.g., paracetamol). The quality of the 14 included studies was variable. We assessed three studies as being at overall risk of high bias, seven at unclear risk of bias, and four at low risk of bias.
Although a number of randomized controlled trials have been undertaken, data were available from only a very limited number of these studies. These limited data suggest that propentofylline may have a beneficial effect on measures of cognitive and global function of people with Alzheimer's or vascular dementia. The unavailability of data, due to failure of Aventis, the manufacturing pharmaceutical company, to release information about unpublished studies prevented a comprehensive systematic review and meta-analysis.
The evidence is current to 15 February 2017. We selected randomised controlled trials comparing influenza vaccine with placebo or no treatment in infants and children aged six months to six years, with or without a history of previous episodes of AOM. We included 11 trials involving 17,123 children. Ten out of 11 trials were funded by vaccine manufacturers. We found a 4% reduction in AOM and about an 11% reduction in the number of antibiotic prescriptions. There was no difference in the number of courses or types of vaccine administered between those who were vaccinated and those who were unvaccinated. Influenza vaccine side effects included an increase in fever, runny nose, and drowsiness. It remains uncertain whether the influenza vaccine reduced visits or admissions to healthcare facilities. Data were insufficient to show that this benefit might be balanced against more serious or rarer side effects from the vaccine. Although we observed a reduction in antibiotic usage, this impact is uncertain because the current practice is to avoid overuse of antibiotics. Coupled with other vaccine safety concerns, the use of influenza vaccine to reduce AOM is not yet justified, and additional research is needed. The overall quality of the evidence was low to moderate.
Authors from Cochrane Oral Health carried out this review and the evidence is up to date to 15 January 2018. A total of 48 randomised controlled trials on 1227 adults were included with five studies evaluating multiple recession-type defects and the rest single gingival recessions. Most trials followed participants for 6 months to 12 months. The review looked at different interventions: free gingival grafts (FGG), coronally advanced flap (CAF) alone or associated to acellular dermal matrix grafts (ADMG), enamel matrix protein (EMP), guided tissue regeneration with resorbable membranes (GTR rm), guided tissue regeneration with non-resorbable membranes (GTR nrm), GTR rm associated with bone substitutes, platelet-rich plasma or fibrin (PRP or PRF), growth factors (rhPDGF-BB) associated to bone substitutes (b-TCP), subepithelial connective tissue grafts (SCTG) or xenogeneic collagen matrix (XCM). We did not find any trials evaluating laterally positioned flaps (LPF). The results of this review have shown that most root coverage periodontal plastic surgery procedures led to gains in reduction of gingival recession. However, we are uncertain about which intervention is the most effective as all studies were judged to be at unclear or high risk of bias. Preferably, subepithelial connective tissue grafts, coronally advanced flap alone or associated with another graft or biomaterial and guided tissue regeneration can be used as root coverage procedures for treating recession-type defects. Limited data exist on how these interventions affect the appearance of the teeth. Adverse effects reported in the studies included discomfort and pain, but these were mainly related to the site where the tissue graft was taken, and occurred mainly within the first week after surgery with no influence on root coverage outcomes. Further research is needed on the results to be achieved from each root coverage periodontal plastic procedure. We judged the quality of the evidence to be low or very low mainly due to problems with the design of the studies.
Study characteristics. Nineteen eligible studies involving 4096 infants met our inclusion criteria. Results. Insufficient evidence exists to support the routine use of high frequency oscillatory ventilation instead of conventional ventilation for preterm infants with lung disease who are given positive pressure ventilation. High frequency oscillatory ventilation is a way of providing artificial ventilation of the lungs that theoretically may produce less injury to the lungs and therefore reduce the rate of chronic lung disease. This review of the evidence from 19 randomised controlled trials showed that although a small protective effect towards the lungs can be seen, this moderate benefit is highly variable between studies and should be weighed against possible harm.
We included five trials, involving 952 participants. Trials of mothers' avoidance of milk, eggs, and other potentially 'antigenic' foods during pregnancy or breastfeeding, or both, provide inadequate evidence about whether such avoidance helps prevent atopic eczema or asthma in the child. Women who avoided eating these foods gained significantly less weight during pregnancy in the one trial reporting on this outcome, raising the possibility of adverse nutritional effects on the mother or fetus. Finally, one small trial reported an inconclusive response of breastfed infants with atopic eczema when their mothers avoided consumption of cow milk and egg.
The studies we included were randomised trials that enrolled babies born at less than 28 weeks' gestation, at birth or soon thereafter, and targeted oxygen saturation (SpO₂) ranges of either 85% to 89% or 91% to 95%, for at least the first two weeks of life. We included five trials, which together enrolled 4965 infants, in this review. There were benefits and harms associated with both the target ranges tested. Neither the lower nor the higher target range had a significant effect on the rate of death or major disability (the main outcome), on major disability alone or on blindness. However, infants in whom the lower oxygen range was targeted had, on average, a 2.8% increased risk of death, compared to the infants in whom the higher oxygen range was targeted. They also had a 2.2% increase in the rate of a serious bowel condition known as necrotising enterocolitis. Conversely, the infants in whom the lower oxygen range was targeted had a 4.2% decrease in the rate of a serious eye problem, retinopathy of prematurity, requiring surgery or other treatments. The trade-offs between these benefits and harms may need to be assessed within local settings when deciding on oxygen saturation targeting policies. We rated the quality of the evidence as high for the key outcomes of death, major disability, the composite of death or major disability, and necrotising enterocolitis. We rated the quality of evidence as moderate for the two eye-related outcomes (blindness, retinopathy of prematurity requiring treatment), giving us confidence that the overall results are reliable.
This review assessed the effects of psychotropic analgesic nitrous oxide (PAN) in treating alcohol withdrawal. All trials were conducted in in-patient settings although PAN is also administered in outpatient settings. The review found that PAN is as effective as sedatives for managing mild to moderate alcohol withdrawal states. Nonetheless, it does not provide strong evidence in favour of the benefits or harms of using PAN over sedatives in managing acute alcohol withdrawal. Further high quality trials should be done before these findings can be confirmed.
We identified two trials (of high risk of bias or systematic error) involving 152 patients randomised to gastrojejunostomy (80) and no gastrojejunostomy (72). In both studies, patients were found to be unresectable during operations aimed at surgical removal i.e. the stomach was opened to remove the cancer but the cancer could not be removed. There was no evidence of any difference in the overall survival, surgical complications, quality of life, or hospital stay between the two groups. The proportion of patients who developed long-term stomach outflow obstruction was significantly lower in the prophylactic gastrojejunostomy group (2.5%) compared with no gastrojejunostomy group (27.8%). The operating time was significantly longer in the gastrojejunostomy group compared with no gastrojejunostomy group by about 45 minutes. Routine prophylactic gastrojejunostomy is indicated in patients with unresectable periampullary cancer undergoing open operation of the stomach. There is no information available currently about the necessity for prophylactic gastrojejunostomy in patients with periampullary cancer diagnosed to be unresectable by investigations such as scans. Further trials of low risk of bias are necessary to assess the role of prophylactic gastrojejunostomy in patients with unresectable periampullary cancer.
Women in the studies took 2 g of strontium ranelate or a placebo (fake tablets or powder). After 2 to 3 years, the number of fractures that occurred and bone mineral density was measured. Bone mineral density is a lab test to measure how dense or strong bones are in the hip, spine or neck. The higher the bone density the better. Benefits of strontium ranelate In women after menopause who have osteoporosis: - strontium ranelate decreases spine fractures: 13 out of 100 women had spine fractures taking strontium ranelate 21 out of 100 women had spine fractures taking a placebo - strontium ranelate may decrease fractures that are not in the spine: 10 out of 100 women had non-spine fractures taking strontium ranelate 12 out of 100 women had non-spine fractures taking a placebo - strontium ranelate increases bone mineral density 1 in 3 women had an increase in spine and hip bone mineral density taking strontium ranelate Harms of strontium ranelate In women after menopause who have osteoporosis: - strontium ranelate did not cause side effects that would make them stop taking it - strontium ranelate did not lead to serious side effects, stomach infections, back pain or death - strontium ranelate increased diarrhea 6 out of 100 women had diarrhea taking strontium ranelate 4 out of 100 women had diarrhea taking a placebo Other research shows that harms could include a chance of blood clots, and seizures, memory loss and consciousness. The cause of these vascular and neurological side effects are not known. This review has several limitations which include difficulty interpreting the change in bone mineral density due to the unique aspects of strontium in bone as well, incomplete follow-up of some patients within the individual trials.
In contrast to the previous version of this review, this update now includes data from one large and six small randomised controlled trials. It allows more definitive conclusions about the potential beneficial or harmful clinical effects of IABP support beyond its immediate haemodynamic effects. Complications such as moderate and severe bleeding were more frequently observed in patients treated with more invasive devices than IABP. Small randomised trials suffered from inadequate power to address deaths and harmful effects of IABP and were biased by frequent cross-over to the more aggressive strategy, early stopping of the trial, or the inclusion of patients with IABP at randomisation. It is most noteworthy that a recently conducted and published large randomised trial showed no evidence for survival benefits of IABP support in patients with infarct-related cardiogenic shock treated by percutaneous coronary intervention (PCI). On the basis of these data, IABP support is no longer strongly recommended by the European Society of Cardiology (ESC) guidelines for treatment of patients with infarct-related cardiogenic shock. Rather, IABP use is based on the personal experience and decision of the physician and the particular circumstances of individual patients.
We included eight studies published between 1964 and 2014. All studies involved people from rheumatology clinics. Studies were conducted in Italy, United Kingdom, United States of America, China, Russia, and Bangladesh. Five studies compared methotrexate against placebo (345 people), and four studies compared methotrexate against another DMARD (leflunomide (61 people), ciclosporin A (35 people), gold (30 people), and sulfasalazine (24 people)). The average age of people included in these studies varied from 26 to 52 years. The average duration of psoriatic arthritis ranged from one to nine years. The dose of methotrexate consisted of 7.5 mg to 25 mg orally, but for most studies, 15 mg was given orally per week. In most western countries, a dose of 15 mg to 20 mg orally per week is normally used in routine practice. After six months of treatment, comparison with placebo (a fake drug) showed that methotrexate resulted in the following (note that one study measured but did not report quality of life, and no studies measured radiographic progression). Proportion who responded to treatment as measured by the Psoriatic Arthritis Response Criteria 16% more people, or 16 more people out of 100, improved with treatment (4% more to 28% more) 37 out of 100 people taking methotrexate improved 21 out of 100 people taking placebo improved Function (lower scores mean better function) Function was improved by 10% (ranging from 3% better to 17% better), or by 0.30 points (ranging from 0.09 better to 0.51 better) on a 0 to 3 scale (this is expected to be meaningful to patients) People taking methotrexate rated their function as 0.7 point People taking placebo rated their function as 1.0 point Disease activity (lower scores mean less active disease) Disease activity improved by 3% (7% better to 1% worse), or by 0.26 points (0.65 better to 0.13 worse) on a 0 to 10 scale People taking methotrexate had a disease activity score of 3.8 points People taking placebo had a disease activity score of 4.06 points Serious adverse events (more events mean more harm) 2% fewer people, or two fewer people out of 100 (5% fewer to 1% more), reported a serious adverse event with methotrexate One person out of 100 people taking methotrexate had a serious adverse event Three out of 100 people taking placebo had a serious adverse event Withdrawals due to adverse events (more events means more harm) 1% more people, or one more person out of 100 (4% fewer to 6% more), withdrew from treatment with methotrexate Six out of 100 people taking methotrexate withdrew Five out of 100 people taking placebo withdrew Low-quality evidence suggests that methotrexate might lead to slightly greater benefit than placebo for some outcomes (e.g. improving function) but may be no better than placebo for other outcomes (e.g. reducing disease activity). We assessed the quality of the evidence as low due to flawed trial design and imprecision (some results are meaningful to patients and some are not). We are uncertain whether methotrexate causes more harm than placebo due to the small number of reported events.
We systematically searched the scientific literature for reports of studies comparing ultra-radical and standard surgery for women with advanced ovarian cancer. We looked for randomised controlled trials, which are regarded as the best type of study, and for non-randomised studies that were analysed using methods that allow for differences between the groups of women receiving different types of surgery. We found only one relevant non-randomised study. It analysed data for 194 women recruited at one centre. Analysis that allowed for the differences in the extent of disease of the women who received the two different types of surgery found better disease specific survival among women receiving ultra-radical surgery. The best estimate was that their risk of death from ovarian cancer was about one third lower than for women who had standard surgery, but it might actually have been anywhere between 60% lower and 4% higher. However, the extent of disease in these women varied a lot so the authors also analysed only the 144 women whose cancer had spread throughout their abdomen. Again, the best estimate was that their risk of death was about one third lower than for women who had standard surgery, but it might have been anywhere between 60% lower and only 2% lower. Although this result seems to suggest that ultra-radical surgery might be better than standard surgery, we need to be cautious as the study was not well designed nor analysed, so it may be over-estimating the real benefits of ultra-radical surgery. The study did not report all deaths, which would have been a more reliable and more important outcome. Neither did it report any differences between the groups in the time before the cancer progressed. It did not report quality of life (QoL) which would be very important to women with this advanced cancer. The cost-effectiveness of this intervention was not investigated. Therefore, we could not reach any definite conclusions about the relative benefits and adverse effects of the two types of surgery. Better designed, large studies are needed in order to compare ultra-radical and standard surgery for women with advanced ovarian cancer.
This review includes 19 randomised trials on banding ligation versus beta-blockers for patients with high-risk oesophageal varices and no history of bleeding. Bias control was unclear in most trials. There was no difference in mortality among the patients randomised to banding ligation compared with beta-blockers. The trials with adequate bias control based on the assessment of randomisation methods found no difference in bleeding rates. The trials with unclear randomisation methods found that banding ligation reduced bleeding. The effect of banding ligation was associated with the duration of follow-up and publication status of the trials. The results of trials with less than 20 months of follow-up found a better effect of banding ligation compared to trials with longer follow-up. Trials published in abstract form were more positive towards the effect of banding ligation than trials published as full paper articles. The combined evidence suggests that banding ligation and beta-blockers may be used as primary prophylaxis in oesophageal varices in adult patients. Additional evidence from trials with adequate bias control and sufficient follow-up is still needed to determine long-term effects.
This review identified that there is currently insufficient high-quality evidence which evaluates the effectiveness of different policies for replacing long-term urinary catheters. Only three randomised clinical trials, which included a total of 107 participants, were eligible and included in this review. These trials evaluated: (i) different time intervals for catheter replacement, (ii) the use of antibiotics to prevent infection and (iii) the use of different cleaning solutions. There was insufficient evidence to suggest that replacing the catheter monthly and when there was a clinical reason to do so reduced bacteria in the urine compared to replacing the catheter only when there was a clinical reason to do so. However, there was not enough evidence to say whether using antibiotics at the time of replacing the catheter for prevention of infection was effective or whether using water to cleanse during catheter replacement was as effective as an anti-bacterial washing solution. None of the trials reported any adverse effects relating to the policies investigated. All three trials which were included in this review were very small with methodological flaws. Therefore new trials are needed in order to definitely answer this research question. The evidence in this review is current up to 19 May 2016.
This review compares the different interface options for CPAP in patients with OSA. Four trials involving 132 people were included. Two studies compared nasal masks with an oral mask called the Oracle, and there did not appear to any significant differences between the two in terms of compliance, sleep study recordings, sleepiness or other symptoms of OSA. One study assessing nasal masks versus nasal pillows (consisting of prongs that rest within the nostrils) showed that patients using the nasal pillows had fewer overall side effects and reported greater satisfaction. The nose mask performed better than the face mask (which covers both the nose and mouth) with one study showing greater compliance and less sleepiness, and was the preferred mask in almost all patients. The choice of interface for a particular person will need to be tailored to the individual. Further trials comparing the many interfaces for CPAP in the treatment of OSA are needed.
However studies have focused on kidney protection rather than over mortality. The aim of this review was to assess the benefits and harms or ACEI and AIIRA therapy in patients with DKD. Fifty studies (13,215 patients) were identified comparing ACEi to placebo, AIIRA to placebo and ACEi to AIIRA. The risk of death from any cause was not significantly reduced with the use of ACEi versus placebo, AIIRA versus placebo or ACEi versus AIIRA. However when we looked at the studies which used the maximum dose tolerated of ACEi rather than the lower, so-called renal doses, there was a significant reduction in the risk of death due to any cause. We were unable to determine which drug provides better protection due to the lack of head-to-head trials.
Three controlled studies have used different gentle rocking motions (irregularly oscillating water beds, regularly rocking bed trays or a vertical pulsating stimulus) to reduce the occurrence of apnea in a total of 49 babies. However, there was no clinically useful reduction of periods of apnea, although only a small number of infants were studied. Shorter breathing pauses were reported to be reduced by one study but it is not thought to be clinically important. No harm has reported to be done to the preterm infants with these interventions.
There have been few trials of treatment for Charcot-Marie Tooth disease. One very small trial of the nerve growth promoting factor, neurotrophin-3, showed possible benefit but needs to be replicated. Trials of exercise, orthosis, creatine and ganglioside injections have been done but did not show significant benefit. These were all too small to identify moderate benefit or harm. Trials of vitamin C for the commonest type of Charcot-Marie Tooth disease are in progress.
In this review update, 74 studies involving 5175 patients with lupus nephritis could be studied. Treatments included intravenous (given through a vein) cyclophosphamide, oral (tablets by mouth) mycophenolate mofetil (MMF), azathioprine, and tacrolimus (used alone or together with MMF). We also found studies of treatments called “biologic” therapies, that have been designed to change very specific parts of the body’s immune system that cause it to attack itself. We looked particularly at key outcomes such as whether treatment prevented patients from needing dialysis and controlled the lupus damage to the kidney tissue (called remission). We also looked at serious side-effects including death, infection, infertility, and hair loss. After combining the available studies, compared with cyclophosphamide, MMF may be better at getting the lupus damage to the kidneys under control. However, the range where the actual effect may suggest that MMF may make little or no difference to disease remission compared to treatment with cyclophosphamide. MMF treatment given with tacrolimus may lead to more disease remission. MMF may result in less hair loss and worse diarrhoea, but we were not certain whether MMF reduces infertility or other serious side effects. MMF was better than azathioprine for preventing kidney disease in the longer term. None of the studies told us whether treatment had any effect on death or need for dialysis, and there was very low certainty of evidence for the use of biologics in patients with lupus nephritis. Patients with lupus nephritis may have similar or slightly better outcomes when treated with MMF or MMF with tacrolimus compared to those patients who receive intravenous cyclophosphamide. We are still not certain which is the best treatment for lupus nephritis to protect against needing dialysis in the longer term.
This review of 16 studies enrolling 809 children found that rhGH increased height in children with CKD by about 4 cm after 1 year and by a further 2 cm after 2 years of treatment compared with no treatment. The frequency of reported side effects of rhGH was generally similar to that of the control group.
The aim of this review was to assess the effectiveness HIV prevention interventions delivered by phone calls compared to the standard way of delivering care. After a comprehensive search of various scientific databases and other resources, we found only one relevant study. This study was done in sexual assault services in South Africa. Study participants were women and girls who were given medication to prevent HIV infection (so called 'post-exposure prophylaxis' or 'PEP') after they had been raped. The participants were divided into two groups: one group of participants only received standard care and participants in the other group were given standard care and support via telephone calls to help them take their HIV prevention medication. Overall, only about one third of the participants took their HIV prevention medication for 28 days. The participants who received the phone calls were not more likely to take their medication than participants who only received standard care. Also, the phone calls did not decrease the number of participants with depression and did not increase the number of participants who read an information pamphlet or returned to collect HIV prevention medication. Only a higher percentage of participants who received the calls used a medication diary compared to the participants who did not receive the calls. No harmful effects of this intervention were reported. We could not find any information about other relevant outcomes, such as participants’ and healthcare providers’ satisfaction with the telephone intervention or costs. We urgently need more studies conducted in various settings comparing the effectiveness of the phone calls to other ways of delivering HIV prevention interventions to prevent new HIV infections.
This review focused on randomised controlled trials (RCTs) of anticoagulants compared with conventional care for the prevention of catheter malfunction patients receiving haemodialysis. We found 27 studies, involving 3003 patients followed for an average six months, which assessed alternative anticoagulant locking solutions, systemic agents and low or no dose heparin. Catheter malfunction were not affected by any of these classes of agents. Subgroup analysis showed that the only agent reducing catheter malfunction was recombinant tissue plasminogen locking solution based on the results of a single study. A significant reduction was observed on the incidence of catheter-related bacteraemia for alternative anticoagulant locking solutions. There was no evidence to suggest that alternative anticoagulants to heparin locking solutions had an effect on death rates or bleeding events, although only a small proportion of studies reported bleeding events. Further high quality information is needed on both potential benefits and safety of alternative approaches to maintaining dialysis access catheter function.
We considered the type of pterygium surgery to be better if it the pterygium returned in a smaller proportion of people at three and six months after the surgery. We searched online databases of published medical articles to find studies that had assigned participants to one of the two surgeries. We included in our review only the studies in which the participants were assigned randomly to their surgery, so that they had an equal chance of being assigned to either one. Study participants could have this growth for the first time (primary pterygium) or could need another surgery because their growth had returned previous surgery. The evidence is current to November 2015. We found 20 studies that compared the two surgeries in a total of 1947 eyes. We combined information from the studies to determine which surgery was better. Six months after surgery, the pterygium returned only one third to over half as often in people who had CAG surgery than in people who had AMT surgery. This difference could not be explained by chance alone. The studies we found did not answer all of our questions. We still want to know the effects of the surgeries on clarity of vision, quality of vision, quality of life and costs. More research studies are needed that answer these questions. The overall quality of the evidence in favor of CAG is low to moderate because of issues in the conduct of the studies and results were sometimes not similar across studies. Future published research may have an impact on the conclusions provided in this review.
Although meditation therapy is widely used in many anxiety-related conditions there is still a lack of studies in anxiety disorder patients. The small number of studies included in this review do not permit any conclusions to be drawn on the effectiveness of meditation therapy for anxiety disorders. Transcendental meditation is comparable with other kinds of relaxation therapies in reducing anxiety, and Kundalini Yoga did not show significant effectiveness in treating obsessive-compulsive disorders compared with Relaxation/Meditation. Drop out rates appear to be high, and adverse effects of meditation have not been reported. More trials are needed.
We searched for evidence (October 2018) and found two trials (involving 99 women) conducted in Canada and the USA. Both trials compared guided imagery with quiet rest. There were no trials comparing guided imagery with no intervention, or other with another non-pharmacological method for hypertension. The two included studies reported different outcomes and the Intervention frequency was slightly different between the two studies. One study performed guided imagery for 15 minutes at least twice daily for four weeks or until the baby was born (whichever came first). The other study involved guided imagery, self-monitoring of blood pressure, and thermal biofeedback-assisted relaxation training for a total of four hours; the women were instructed to practice the procedures twice daily and complete at least three relaxation breaks each day. The control groups between the two studies were similar - one used quiet rest and the other used quiet rest as bed rest. Neither trial reported data for our main outcomes of interest: severe hypertension, severe pre-eclampsia, or death of the baby during birth or within the first week of life. The trials provided data for only one of our secondary outcomes of interest. Low-certainty evidence from the one trial (69 women) suggests that, compared with quiet rest, guided imagery may make little or no difference in the use of antihypertensive drugs. We included two small trials comparing guided imagery with quiet rest. We did not identify any trials comparing guided imagery with no intervention, or another non-pharmacological treatment for hypertension. The available evidence for this review is sparse and the effect of guided imagery for treating hypertension during pregnancy (compared with quiet rest) remains unclear. The included trials did not report on any of the main outcomes in this review and only provided low-certainty evidence on the uncertain effect on the use of antihypertensive drugs. There is insufficient evidence to inform practice about using guided imagery for hypertension in pregnancy. Large and well-designed studies are needed to identify the effects of guided imagery on hypertension during pregnancy and on other relevant outcomes associated with the short-term and long-term health of mothers and their babies. The trials should also consider the use and costs of health services.
We searched medical databases for clinical trials of enzyme replacement therapy in children with Pompe disease. We found no randomised trials (where people taking part in the trial have equal chances of being in the treatment or the control group) comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo (a 'dummy' drug). We found one trial (18 children) that compared two doses of recombinant human alglucosidase alfa (an enzyme replacement therapy): 20 mg/kg every two weeks (low dose) and 40 mg/kg every two weeks (high dose). The duration of treatment ranged from 52 weeks (the length of the original study) to up to three years (including the extension phase of the study), with a median (the middle number) duration of treatment being 2.3 years. There were very limited numerical results available by dose group, the trial showed no evidence in favour of a high dose as opposed to a low dose. It described that the clinical responses including cardiac function, motor development (development of a child's muscles and their ability to move around and manipulate their environment), as well as the proportion of children that were free of invasive ventilation,were similar in the two groups (low-quality evidence). Long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival (time without requiring a machine to help with breathing) and improved cardiomyopathy (heart disease) (low-quality evidence). In relation to the number of children experiencing one or more infusion-related events, there was no significant difference between the different dose groups (low-quality evidence), although, of note, at 52 weeks, five children in the low-dose group experienced a total of 41 mild or moderate (none were severe) infusion-related events and the six children in the high dose-group experienced a total of 123 infusion-related events. By the end of the extension phase, five children in the low-dose group experienced a total of 47 infusion-related events and the six children in the high-dose group experienced a total of 177 infusion-related events. New trials should be undertaken with adequate number of participants to detect effectiveness and safety at different doses of alglucosidase alfa. The main clinical outcomes (i.e. cardiac function, time to ventilation, survival, motor development and side effects) should be standardized when evaluated and reported. The evidence that this small trial provided to the review was of low quality. The trial was supported by the Genzyme Corporation.
We found six randomised controlled studies involving 546 women who were pregnant with one baby and were showing signs of preterm labor at between 23 to 34 weeks' gestation. We graded the following evidence as mainly low quality because of the low number of women in the studies and a wide variation in findings. We found that the number of births before 37 weeks may be slightly reduced when women and their doctors know the results of the FFN test (20.7% versus 29.2%; 5 trials; 434 women). However, knowledge of FFN results may make little or no difference for the other outcomes with available data, including: maternal hospitalization (5 trials; 441 women); use of uterine relaxants (tocolysis) to try to prevent labor; earlier preterm births; women’s gestational age at delivery; babies with a birthweight less than 2500 g; newborn deaths; the number of babies with respiratory distress syndrome; giving steroids to mature the unborn babies’ lungs; and number of days in a neonatal intensive care unit (NICU). This review of six studies did not find enough evidence to say whether or not the FFN test should be used in the management of women showing signs of preterm labor. A screening test such as FFN can only be considered effective if interventions based on the screening results, such as giving drugs to relax the uterus, reduce the number of preterm births. Further research should be encouraged.
In addition, radiotherapy to the abdomen was not associated with improved survival, as we found in one trial that there was no difference in the risk of death and disease progression in women who received whole abdominal irradiation and chemotherapy, after adjustment for age and stage of disease. Previous studies have shown that doxorubicin, despite being established in the treatment of uterine carcinoma, does not seem to be highly active. Adverse events were comprehensively reported for the comparisons of combination therapy and ifosfamide and whole body irradiation and chemotherapy. More women experienced side effects when they received combination therapy than ifosamide alone and chemotherapy than whole body irradiation. The effect of therapy on quality of life was not reported in any of the trials.
We searched for studies until June 2016, and found 13 studies (839 individuals). Most studies (61.5%) included only female participants. Average age of participants was 41 years (minimum 32 to maximum 56 years). According to the inclusion/exclusion criteria, most participants were not doing exercises before starting the study. Aerobic interventions were compared with controls (wait list, treatment as usual, daily activities as usual) over six to 24 weeks. On average, exercise sessions were provided two to three times per week for 35 minutes each session. Exercises involved walking, cycling, running, and doing low-impact aerobics and aquacise. Participants exercised at different intensities, starting light and increasing as the study progressed. All programs were supervised. Key results at the end of treatment The findings of aerobic exercise compared with no exercise control were prioritised and are presented fully here. Moderate-quality evidence revealed that aerobic exercise improved HRQL, and low-quality evidence showed improvement in physical function and decreased pain, fatigue, and stiffness compared with control. Similar numbers of people dropped out of the aerobic interventions group and the comparison group. Minor adverse events were reported, but reporting was inconsistent in these studies. Four studies explored long-term effects at 24 to 208 weeks after the intervention ended. They reported benefits for pain and physical function among exercisers and noted no other effects. Best estimates of what happened in people with fibromyalgia when they did aerobic exercise compared with when they received control interventions Each outcome below was measured on a scale from 0 to 100, on which lower scores were better. HRQL after 12 to 24 weeks: People who exercised were 7% better (or 7 points, ranging from 3 to 13 points) and rated their HRQL as 48 points versus 56 points in the control group. Pain after 6 to 24 weeks: People who exercised were 11% better (or 11 points, ranging from 4 to 18 points) and rated their pain as 56 points versus 65 points in the control group. Fatigue after 14 to 24 weeks: Those who exercised were 6% better (or 6 points, ranging from 12 better to 0.3 worse) and rated their fatigue as 63 points versus 68 points in the control group. Stiffness after 16 weeks: Those who exercised were 8% better (or 8 points, ranging from 1 to 15) and rated their stiffness as 61 points versus 69 points in the control group. Physical function after 8 to 24 weeks: The aerobic exercise group was 10% better (or 10 points, ranging from 15 to 5) and participants rated their physical function as 37 points versus 46 points in the control group. Other results: Withdrawal from treatment A total of 20 out of 100 people dropped out of the aerobic group compared with 17 out of 100 from the control group (3% more, ranging from 3% fewer to 12% more) for any reason. Adverse events We do not have precise information about adverse events associated with aerobic exercise. Some reports describe increased pain or fatigue, and one of the 496 participants doing aerobic exercise experienced a foot bone (metatarsal) stress fracture. This may have happened by chance. Quality of the evidence Evidence shows that aerobic exercise may improve HRQL, pain, stiffness, and physical function, and probably leads to similar numbers of people dropping out from each group. Aerobic exercise does not seem to improve fatigue. The quality of the evidence was considered to be low or moderate because of the small numbers of people included in the studies, some issues involving study design, and low certainty of results.
For this review we only identified one study that met the inclusion criteria (current until 29 March 2017). This study randomised 200 participants (162 included in analysis) and compared surgical lumbar sympathectomy with the prostaglandin, iloprost, in people with Buerger's disease, a form of PAD, and followed participants for 24 weeks. This study found evidence of increased complete ulcer healing without rest pain or major amputation in the participants who received intravenous prostaglandin compared with those that received surgical lumbar sympathectomy. However, those who received prostaglandins were more likely to report adverse events such as headache, flushing, nausea and abdominal discomfort. There were no reported deaths in either treatment group. The single included study did not report on other planned outcomes for this review such as walking distances and quality of life or functional status. The single study was limited to the specific form of PAD known as Buerger's disease, and to surgical lumbar sympathectomy, making it difficult to generalise the findings to all types of PAD and all methods of lumbar sympathectomy. Overall, the study had little risk of bias due to design. Blinding of the participants and those that administered the treatment would be impossible, but there was no mention of blinding of the people who evaluated the outcomes, which would have been a possibility. Due to this, we rated the outcomes that had subjective measures (measures that can be influenced by or based on personal beliefs or feelings), such as relief of rest pain as unclear risk of bias, but the outcomes that had objective measures (measures that are not influenced by or based on personal beliefs or feelings) such as ulcer healing, amputation and mortality as low risk of bias. Also, there was a large number of participants not included in the analysis (38 of the 200, 19%), in both groups, with inadequate reasons as to why, so we rated bias due to incomplete outcome data as unclear. The quality of the evidence, therefore, was low for the outcomes evaluated as the number of participants included was low and only a single study reported evidence.
The review identified two trials of sapropterin dihydrochloride; one in children and adults with no restricted diet and one in just children whose diet was restricted. The trials used different doses of sapropterin dihydrochloride (10 mg/kg/day and 20 mg/kg/day). We could not combine any data due to different formats of presentation. We found evidence to show that some people with mild or moderate phenylketonuria can benefit from the use of sapropterin dihydrochloride in the short term; the concentration of blood phenylalanine was lowered after treatment in both trials. The trial with the higher dose also measured the outcome change in protein tolerance. It reported an increase in protein tolerance in response to sapropterin. There were no adverse effects associated with the use of sapropterin dihydrochloride in the short term. We found no evidence on the effects of long-term treatment. We could not draw any conclusions on its benefits in severe phenylketonuria.
Although the incidence of invasive pneumococcal disease is variable across the world, the rate of serious illness or death is high in children who get this infection. The Streptococcus pneumoniae (pneumococcus) organism colonizes the upper respiratory tract and can cause bacteremia, meningitis, pneumonia and other lower respiratory tract, and upper respiratory tract infections, including otitis media and sinusitis. Newborn vaccination schedules of three primary doses with a booster dose could reduce the impact of pneumococcal disease in immunized children, but these vaccinations have no protective effect in infants less than three months of age. Maternal pneumococcal immunization during pregnancy may be a way of preventing pneumococcal disease during the infant's first months of life. We included seven randomized controlled trials. A total of 919 pregnant women participated in the six randomized controlled trials that contributed data to this review. The trials compared 23-valent pneumococcal polysaccharide vaccine with control vaccine. All women received a single injection of pneumococcal or control vaccine (where used). The women’s mean gestational age at the time of immunization was between 27 and 38 weeks, where stated. Only two trials with 241 pregnancies reported on neonatal infections. This was not enough information to say whether pneumococcal vaccination during pregnancy led to fewer infant infections. Two trials with 146 pregnancies reported on infant nasal carriage of pneumococci (pneumococcal colonization), which was not enough evidence to show an effect in reducing colonization at two to three months of age or six to seven months of age. The included trials were of reasonable quality. There was no difference between pneumococcal vaccine and control vaccine for tenderness at the injection site. No serious adverse events were reported in the trials.
This review includes four randomised trials involving 1429 participants. All four trials compared verteporfin therapy to 5% dextrose water (placebo treatment). Photodynamic therapy reduces the risk of vision loss caused by "wet" age-related macular degeneration. More people treated with verteporfin also experienced improvements in vision compared to the placebo group, however, the absolute numbers experiencing vision improvement after this treatment was low (80 per 1000). A small number of people may experience acute vision loss within one week after treatment (in approximately 1 in 100 people) and infusion related back pain can occur (in approximately 1 in 50 people).
We searched the medical literature widely up to February 2016 for studies that investigated the pain-relieving effect of sucrose for minor medical procedures in newborn full-term and premature babies. We included randomised controlled trials only, as these provide the most reliable medical evidence. We identified 74 studies that reported on a total of more than 7000 infants in this Cochrane Review. Thirty-eight studies included full-term babies only, 31 included premature babies only, and five included both full-term and premature babies. Heel lance was the painful procedure in 38 studies, and venipuncture in nine; the remaining studies investigated a wide variety of other minor painful procedures. The studies used a variety of delivery methods for the sucrose solution (oral syringe, dropper or sucrose-dipped pacifier), as well as a range of concentrations and volumes of dose. Sucrose treatment was compared with giving the babies a similar volume of water, a pacifier, routine care, breastfeeding, 'facilitated tucking' (holding the infant in a flexed position with arms close to the body and hands placed to promote sucking), laser acupuncture, swaddling, warmth, anaesthetic cream for the skin (EMLA), or a combination of these. The studies used a range of pain assessment scales to measure their results. We did not identify any studies that received funding from the industry. There was high-quality evidence that sucrose reduces different measures of newborn pain during heel lance, venipuncture and intramuscular injection. However, sucrose does not provide effective pain relief during circumcision. There is conflicting evidence for whether sucrose reduces pain for other minor painful procedures and further research is needed to investigate these more thoroughly. Twenty-nine studies reported on adverse events (harms of the sucrose and other treatments) and found that the number of minor adverse events (e.g. choking or gagging) was very low, and was similar in the different groups (so not attributable to the sucrose treatment). No major adverse events were reported. Although sucrose has been widely studied as a pain reliever for newborn babies, most studies have included few babies and have used many different measures of pain to assess its effectiveness. We identified high-quality evidence that sucrose reduces pain for heel lance, venipuncture and intramuscular injection. The quality of evidence was low or moderate in favour for the use of sucrose for other painful procedures.
This review was conducted to examine the efficacy and safety of acupuncture in treating insomnia. Thirty-three randomised controlled trials were eligible for inclusion in the review, involving 2293 participants. We considered all studies to have a high risk of bias. They were diverse in the types of participants, acupuncture treatments and sleep outcome measures used, which limited our ability to draw reliable conclusions. Currently there is a lack of high-quality clinical evidence to inform us about the efficacy and safety of acupuncture.
This review shows that PGS in fact decreases live birth rates in women of advanced maternal age and in women with repeated IVF failure. PGS should not be applied in routine patient care. New forms of PGS that perform the procedure at other stages of development and/or use a different method of analysis should first be evaluated in clinical trials before being introduced into clinical practice.
We included three randomised controlled studies (involving 97 women). The quality of the studies was variable and a number of this review's important outcomes were not reported in the trials. Two studies compared in-utero fetal tracheal occlusion with standard postnatal repair, but differences between the two studies meant that we were unable to combine the data in our analyses. Neither study reported on perinatal deaths. In single studies, in-utero fetal occlusion was associated with a slightly lower gestational age at birth but no clear difference in the risk of preterm birth before 37 weeks; the occurrence of pulmonary hypertension was reduced. there was no difference between groups in terms of preterm rupture of membranes < 37 weeks or maternal infectious morbidity and there were no maternal blood transfusions. Long-term infant survival was improved with in-utero tracheal occlusion in one study, but not in the other. In the third study, antenatal corticosteroids were compared with placebo and there was no difference in the number of perinatal deaths. Nor was there any difference in terms of the number of days that babies were given mechanical ventilation or the number of days babies spent in hospital. We conclude that the current evidence is too limited by small numbers of pregnancies and the variable methodological quality of the trials to recommend intervention (treatment) in pregnancy for women and their unborn babies with CDH. Further high-quality trials are needed in this area. WIth regard to the administration of antenatal corticosteroids, there remains a gap in current research, and a large, high-quality trial should be undertaken to answer this unresolved question. More studies are needed to further examine the effect of in-utero fetal tracheal occlusion on important neonatal outcomes and long-term infant survival and health. Long-term follow-up is of particular importance, and should include morbidity and mortality measures. Further studies should examine the benefits of an in-utero intervention in relation to the severity of the congenital diaphragmatic hernia (i.e. moderate and severe). Indeed, there are three ongoing studies, being conducted by European, North and South American fetal medicine centres, which will contribute to this gap. Ongoing research and any implementation into clinical practice should include standardisation of the procedure, inclusion criteria and long-term childhood follow-up.
We found two trials, which included around 350 men, although information was available for only 339 men in one trial. Evidence was not sufficient to show whether invasive urodynamic tests led to better patient outcomes. Some evidence suggests that these tests did alter management decisions, resulting in fewer men undergoing surgery. No evidence indicates whether this change in management led to fewer symptoms in men after treatment, and it is not known whether patients reported a better quality of life. No information obtained from the included trials reveals how common side effects were in those undergoing invasive urodynamic testing. Not enough information from trials is available regarding the benefits of invasive urodynamic testing for men with voiding dysfunction. More research is needed in which people are randomly assigned to treatment decisions based on their symptoms, physical examination findings and results of non-invasive tests alone, or based on the extra information provided by invasive urodynamic tests. Future studies will help healthcare providers determine whether patients benefit from these extra tests, and whether the tests provide good value for healthcare systems.
The authors of this review sought to identify every study where people with an abdominal injury were randomised to surgery or observation. The authors searched a variety of medical databases but only identified 2 studies, involving 51 and 63 people respectively, both of which took place in Finland and were conducted by the same researchers. Both studies included people with penetrating abdominal injuries, from having been stabbed. The review authors considered both studies to be at moderate risk of bias, since only part of the randomisation process was described and the study protocols were not available to enable full assessment of overall quality. In one study (1992-1994) people received either an observation protocol or mandatory surgery. None of the people in the study died, and there was no difference in the number of people with medical complications between the study groups. One of the harms mentioned by the study authors was that surgery was performed on some people who did not actually need it. Unnecessary surgery can subject people to potential complications. In the other study (1997-2002) people received an observation protocol or diagnostic laparoscopy (minimal surgery). No one died in either group, and there were no differences between the groups in the number of surgeries needed. There were no unnecessary surgeries in either group. Based on the findings of these two small studies, there is no evidence to support the use of surgical management over an observation protocol for people with abdominal trauma showing no signs of bleeding or infection. The authors recommend that future randomised controlled studies clearly report the type of injury, number of damaged organs, extent of damage of internal organs, and complications in the people included.
We performed a comprehensive literature search of the standard medical databases (from database inception to February 2019) in consultation with the Cochrane Gynaecology and Fertility Group Information Specialist, for all randomised controlled trials (studies in which participants are assigned to a treatment group using a random method) investigating the efficiency of NSAIDs compared to the use of placebo or no treatment or compared to each other in infertile women undergoing IVF. We searched for and included studies irrespective of language and country of origin. Two review authors independently selected and evaluated studies, extracted data, and attempted to contact the authors of studies for which data were missing. We found 11 studies (2384 women); data were not available in one study, so we analysed data on 1884 patients; two studies were published as abstracts in international conference reports; and we found one ongoing trial that met our inclusion requirements. We are uncertain of an effect on ongoing pregnancy and miscarriage when NSAIDs were compared to placebo/no treatment. Results suggest that if the chance of ongoing pregnancy and miscarriage following placebo or no treatment is assumed to be 15% and 21%, respectively, the chance following the use of NSAIDs is estimated to be between 12% and 24%, and 7% and 27%, respectively. Only one study compared piroxicam with indomethacin: we are uncertain of an effect on ongoing pregnancy and on miscarriage. The evidence suggests that if the chance of ongoing pregnancy following indomethacin is assumed to be 20%, the chance following the use of piroxicam is estimated to be between 13% and 40%; while for miscarriage, the evidence suggests that if the chance following indomethacin is assumed to be 12%, the chance following the use of piroxicam is estimated to be between 5% and 27%. Concerning the secondary outcomes, we are equally uncertain of any effect. Currently we are uncertain of an effect of the routine use of NSAIDs as co-treatments in infertile women undergoing assisted reproduction in order to improve pregnancy rates. This is based on available data from randomised controlled trials, where no single outcome reported in the studies demonstrated a benefit with their use. The quality of the evidence was very low for all outcomes. This is because of several limitations including poorly reported study methods, imprecision, small study numbers and low numbers of events reported.
We found two randomised trials of graduated compression stockings, involving 2615 participants, and two small trials of intermittent pneumatic compression involving 177 participants. Graduated compression stockings were no better than 'best medical treatment' in reducing the risk of DVT after stroke. Stockings caused more skin problems (for example ulcers and blisters) on the legs. Intermittent pneumatic compression appeared promising but was not proven to be definitely beneficial. The evidence does not support routine use of graduated compression stockings or intermittent pneumatic compression in patients with a recent stroke. The trials that are ongoing at present should provide reliable evidence on the benefits and harms of intermittent pneumatic compression.
We searched for studies comparing women who got emergency contraception in advance to women who got it in standard ways. We examined whether these groups had different rates of pregnancy or sexually transmitted infections. We also studied how often and how quickly both groups used emergency contraception. Finally, we looked at whether advance provision of emergency contraception changed sexual behavior. Studies showed that the chance of pregnancy was similar regardless of whether or not women have emergency contraception on hand before unprotected sex. Women who had emergency contraception in advance were more likely to report use of the medication, and to use it sooner after sex. Having emergency contraception on hand did not change use of other kinds of contraception or change sexual behavior.
An extensive search of the medical literature databases was performed (current up to 29 January 2019). Only one completed RCT was found. In the published RCT, 30 PAAs were treated (15 by the endovascular technique and 15 by the surgical technique). Each case was followed up for a minimum of four years. In the group of participants treated using the endovascular technique there were two blockages. One case was re-stented and the other case required a surgical bypass. In the surgical group too, there were two blockages, which did not require any treatment. There were no limb losses. The time taken to complete the procedure and the length of hospital stay were shorter in the endovascular group. No information on wound complications was given in the trial report. The major limitation of this study was that there were only 15 PAAs in each group so our certainty in the evidence is downgraded from high to moderate. Due to the limitations of the current evidence, we are unable to determine the effects of an endovascular stent graft versus conventional open surgery for the treatment of asymptomatic PAAs. A larger multicenter clinical trial is required so we can be more confident in the findings. We cannot say if there was a clear overall benefit on patency to either group (moderate-certainty evidence). As both operating time and hospital stay were reduced in the endovascular group (moderate certainty evidence), it may represent a viable alternative to open repair of PAA.
We included trials that involved both types of participants. The review found all randomised controlled evaluations of the effects of CBT on men's physical violence to their female partners worldwide, but there were only six small trials with a total of 2343 participants that met the inclusion criteria. The results of four of these trials, which compared men who received CBT with men getting no treatment, were combined. This was not able to show us whether or not CBT was better than no treatment. Similarly, the individual results of the other two trials, which compared CBT with another treatment, were inconclusive. Overall, the evidence from the included studies is insufficient to draw any conclusions.
The results of the review show that in general talking therapies are more effective than no treatment. There was no strong evidence to support one talking therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, there was some low-quality evidence in favour of cognitive behaviour therapy (CBT), psychodynamic therapy and supportive psychotherapy over other talking therapies for short-term remission and short-term reduction in symptoms. The results concerning supportive psychotherapy should, however, be treated with caution because of the small amount of evidence available about this treatment. On the other hand, beyond the evidence regarding its efficacy, psychodynamic therapy also showed promising results in terms of tolerability: as a way of assessing how well people tolerated the talking therapies, we assessed short-term dropout rates. We found that there were fewer dropouts in psychodynamic therapy and third-wave CBT, suggesting that people tolerate these therapies better than other therapies. More high-quality research is needed to be able to fully compare the effectiveness of different talking therapies. In particular, more new studies are needed that compare the specific talking therapies CBT, psychodynamic therapy and supportive psychotherapy for the treatment of panic disorder with or without agoraphobia.
After searching the medical literature up to 6 June 2013 we found two studies The first study (120 participants) compared enriched skim milk powder (with peptides with probable anti-inflammatory effect) to standard skim milk and to lactose powder, and the second study (40 participants) compared vitamin C with allopurinol - a drug commonly used in gout. In the first study, the enriched milk aimed to reduce the frequency of gout attacks, while in the second study the vitamin C aimed to reduce the uric acid levels in blood. People with gout enrolled in both studies were predominantly middle-aged men; in the skim milk study, participants with gout appeared severe as they had very frequent attacks and 20% to 43% presented with tophi, while in the vitamin C study, participants appeared similar to ordinary participants with gout. Gout attacks People who consumed enriched skim milk powder had 0.21 fewer gout attacks per month at three months (from 0.76 fewer to 0.34 more), or 2.5 fewer gout attacks per year: - People who consumed enriched skim milk powder had 0.49 gout attacks per month (or six gout attacks per year). - People who consumed standard skim milk powder or lactose had 0.70 gout attacks per month (or eight gout attacks per year). Withdrawals due to adverse events 4 more people out of 100 who consumed enriched skim milk powder discontinued the supplement at three months (4% more withdrawals). - 18 out of 100 stopped consuming enriched skim milk powder. - 14 out of 100 stopped consuming standard skim milk powder or lactose. Pain reduction, serum uric acid (sUA) levels and physical function were uncertain. Effect on tophus regression was not measured. Serum uric acid levels - People who consumed vitamin C showed an sUA level reduction of 0.014 mmol/L after eight weeks (or 2.8% sUA reduction) - People who were administered allopurinol showed an sUA level reduction of 0.118 mmol/L after eight weeks (or 23.6% sUA reduction). There were no reports of side effects or withdrawals due to side effects in the vitamin C or allopurinol treatment groups. Effects of vitamin C on gout attacks, pain reduction, physical function and tophus regression were not measured. Low-quality evidence from one study indicated enriched skim milk, compared with standard skim milk or lactose powder, may not reduce the frequency of gout attacks or improve physical function or uric acid levels, but may reduce pain. Further research is likely to change these estimates. We do not have precise information about side effects and complications, but possible side effects may include nausea or diarrhoea. Compared with the commonly used medicine allopurinol, low-quality evidence from one study indicated the effect of vitamin C in reducing sUA levels is smaller and probably clinically unimportant. Other possible benefits of vitamin C are uncertain, as they were not evaluated in the study. No side effects were reported. Further research is likely to change these estimates.
Two completed randomised controlled trials were identified. One trial was considered to be of good quality whilst the second trial was of poor quality. The two trials commenced prior to the widespread use of the prostate-specific antigen (PSA) blood test as a screening test for prostate cancer, and hence did not involve many men with PSA-detected cancers. Ongoing trials (PIVOT; ProtecT; START) will provide evidence of the comparative effects of RP and observation protocols for men with PSA-detected cancers. The one good quality trial included in this review involved men with cancers detected by methods other than screening who were randomly allocated to either RP or WW and followed up for 12 years. This single trial does not provide sufficient evidence to allow confident statements to be made about the magnitude of any beneficial and harmful effects of RP compared with WW for men with clinically detected prostate cancers. The trial results indicate that RP is likely to reduce the risks of overall mortality, prostate-cancer mortality and distant metastases (cancer spread) compared to WW, but the magnitude of the effect is unclear. Furthermore, the risk reductions appear to have been limited to men less than 65 years of age. This trial also provides evidence that RP increases the risks of erectile dysfunction and urinary leakage. However, because of the manner in which the data on adverse effects were collected in the trial, confident statements cannot be made about how frequently these adverse effects occur. In addition, nerve-sparing surgery, which has the potential to reduce these complications, was not routinely performed on participants in the trial. A shared approach to decision-making is required whereby patients and their healthcare providers openly discuss the patient's personal values, preferences, and the limitations of the available evidence on potential benefits and potential harms of these treatment options.
The evidence is current to July 2013. This update includes 24 new studies, and this review includes 90 studies overall. The studies included people who smoked and people who had recently quit smoking. There were 65 trials of bupropion, which is licensed for use as a smoking cessation medication under the trade name 'Zyban'. There were ten trials of nortriptyline which is a tricyclic antidepressant which is not licensed specifically for smoking cessation. We only included studies which measured long term quitting (whether or not people had quit smoking at six months or longer from the start of the study). Trials of bupropion (Zyban) for smoking cessation show high quality evidence that it increases the likelihood of a quit attempt being successful after at least six months (44 trials, over 13,000 participants). The side effects of bupropion include insomnia, dry mouth and nausea and rarely (1:1000) seizures and perhaps psychiatric problems, but the last is unclear. There is also moderate quality evidence, limited by a relatively small number of included studies and participants, that the antidepressant nortriptyline increases quit rates (six trials, 975 participants). The side effects of this medication include dry mouth, constipation, nausea, and sedation, and it can be dangerous in overdose. Selective serotonin reuptake inhibitor antidepressants (for example, fluoxetine), monoamine oxidase inhibitor antidepressants (for example, selegiline), and the antidepressant venlaxafine have not been shown to help smoking cessation, nor has the herbal therapy St John's wort, or S-Adenosyl-L-Methionine (SAMe), a dietary supplement that is thought to have antidepressant properties. The way in which bupropion and nortriptyline might work is not fully understood. Both appear to help people quit smoking whether or not they have a history of depression, or have depressive symptoms when they stop smoking. The likelihood of quitting using bupropion or nortriptyline appears to be similar to that for nicotine replacement therapy, but the likelihood of quitting using bupropion appears to be lower than the likelihood of quitting using varenicline.
Five randomised controlled trials enrolling 302 infants met the inclusion criteria. In an infant with tongue-tie and feeding difficulties, surgical release of the tongue-tie does not consistently improve infant feeding but is likely to improve maternal nipple pain. Further research is needed to clarify and confirm this effect. The quality of the evidence is very low to moderate because overall only a small number of studies have looked at this condition, the total number of babies included in these studies was low and some studies could have been better designed.
This systematic review showed that this drug does not increase the number of remissions but increases the number of patients that withdrew from the included studies due to side effects. The methodological quality of the included studies was high. Further studies of this agent for the treatment of active Crohn's disease are unlikely to be undertaken.
We found 21 randomised controlled studies (clinical studies where people are randomly put into one of two or more treatment groups) comparing various drugs plus a behaviour changing intervention such as diet, exercise or both (= intervention groups) usually with placebo (a pretend drug) plus a behaviour changing intervention (= control groups). We also identified eight ongoing studies (studies which are currently running but not completed yet). A total of 2484 children and adolescents took part in the included studies. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up ranged from six months to 100 weeks. The included studies investigated metformin (10 studies), sibutramine (six studies), orlistat (four studies) and one study group evaluated the combination of metformin and fluoxetine. The ongoing studies are investigating metformin (four studies), topiramate (two studies) and exenatide (two studies). Most studies reported on body mass index (BMI) and bodyweight: BMI is a measure of body fat and is calculated from weight and height measurements (kg/m2). In children, BMI is often measured in a way that takes into account sex, weight and height as children grow older (BMI z score). The average change in BMI across control groups was between a 1.8 kg/m2 reduction to a 0.9 kg/m2 increase, while across all intervention groups the average reduction was more pronounced (1.3 kg/m2 reduction). The same effect was observed for weight change: on average, children and adolescents in the intervention groups lost 3.9 kg more weight than the children and adolescents in the control groups. Study authors reported an average of serious side effects in 24 per 1000 participants in the intervention groups compared with an average of 17 per 1000 participants in the control groups. The numbers of participants dropping out of the study because of side effects were 40 per 1000 in the intervention groups and 27 per 1000 in the control groups. The most common side effects in the orlistat and metformin studies were gut (such as diarrhoea and mild tummy pain). Common side effects in the sibutramine trials included increased heart rate (tachycardia), constipation and high blood pressure. The fluoxetine study reported dry mouth and loose stools. One study reported health-related quality of life (a measure of physical, mental, emotional and social functioning) and found no marked differences between intervention and control. No study reported the participants' views of the intervention or socioeconomic effects. Only one study reported on morbidity (how often a disease occurs in a specific area) associated with the intervention, where there were more gallstones after the orlistat treatment. Study authors reported one suicide in the orlistat intervention group. However, studies were not long enough to reliably investigate death from any cause. No study investigated drug treatment for children who were only overweight (obese children have a much higher weight, BMI or BMI z score than children being overweight). This evidence is up to date to March 2016. The overall certainty of the evidence was low or very low, mainly because there were only a few studies per outcome measurement, the number of included children or adolescents was small, and due to variation in the results of the studies. In addition, many children or adolescents left the studies before the study had finished.
We found 15 trials including 39,908 people that investigated whether blood pressure-lowering drugs reduce sudden death. This review presents moderate-quality evidence to show that blood pressure-lowering drugs reduce heart attacks but do not appear to reduce sudden cardiac death. This suggests that sudden cardiac death may not be caused primarily by heart attack. Continued research is needed to determine the causes of sudden cardiac death.
The trials were different in terms of type of breathing exercises performed, number of participants enrolled, number and duration of sessions completed, outcomes reported and statistical presentation of data. As a result, we were not able to compare the results from these trials using a meta-analysis for all outcomes. Meta-analysis was possible for only two outcomes (asthma symptoms and change in Asthma Quality of Life Questionnaire—AQLQ), each of which was reported in only two studies. Both meta-analyses showed a significant difference favouring breathing exercises. The methods used to conduct these studies were not as well reported as we would have liked, and so the quality of the trials was unclear. Overall the quality of the evidence included in the review was very low. Even though individual trials reported positive effects of breathing exercises, no conclusive evidence in this review supports or refutes the efficacy of such intervention in the treatment of adult patients with asthma.
We included four trials that had a limited number of patients (388) and assessed four different interventions: human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate with heparin or placebo. Two trials included patients either with or without leukemia. The other two trials only included patients with leukemia. The studies were published between 1989 and 2007, and were conducted in Japan, Italy and the Netherlands. All trials have a high risk of bias. There were no deaths reported in a trial comparing dermatan sulphate with heparin. Two small trials which included patients with leukemia only (22 participants) reported bleeding data. These results were not compiled due to inconsistency in the measurement and reporting of that outcome. One trial found very low quality evidence that tranexamic acid compared with placebo reduces bleeding in leukemia patients. On the contrary, there is no evidence that dermatan sulphate compared with placebo reduces new events of hemorrhagic diathesis in patients with leukemia. Saftey profile is inconclusive. No thromboembolic complications were reported in both the trials. These trials did not report overall mortality, resolution of respiratory failure, renal failure and shock. Accordingly, the clinical benefits and harms of the human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate are unknown in this population. The confidence in the results of this review is very low. The studies have limitations in the way they were designed and executed. Moreover, the limited number of patients included in the studies led to imprecise results. Well conducted larger studies will provide more information about the effect of human activated protein C, recombinant human soluble thrombomodulin, tranexamic acid and dermatan sulphate for treating DIC in patients with acute or chronic leukemia. This plain language summary is current as of 7 May 2015. Search date: 7 May 2015
The evidence is up to date to 23 March 2017. We found five clinical studies involving 825 adults with mild to moderate hearing loss who were randomly given either hearing aids, no hearing aids or placebo hearing aids. Studies involved older adults with the average age within studies between 69 and 83 years. The duration of the studies was between six weeks and six months. We found evidence in three studies that hearing aids have a large beneficial effect in improving the ability of adults with mild to moderate hearing loss to take part in everyday situations. Hearing aids have a small beneficial effect in improving general health-related quality of life, such as physical, social, emotional and mental well-being, and have a large effect in improving the ability to listen to other people. Only one study attempted to measure harms due to hearing aids. None were reported. We judged the evidence that hearing aids improve the ability to take part in everyday situations, improve general health-related quality of life and improve listening ability to be of moderate quality. This means that while we are reasonably confident that the reported benefits of hearing aids are real, there is a possibility that if further studies are conducted the size of the benefit might differ. We judged the quality of evidence for harms to be very low, because this was only measured in one small study. We found that hearing aids improve the ability of adults with mild to moderate hearing loss to take part in everyday life, their general quality of life and their ability to listen to other people. If an adult with mild to moderate hearing loss seeks help for their hearing difficulties, hearing aids are an effective clinical option. It is important that future studies measure benefits consistently and report benefits separately for different age groups, genders, levels of hearing loss and types of hearing aids.
This review studied whether mobile phone applications such as Short Message Service (SMS) and Multimedia Message Service (MMS) can be useful to send information to patients about their test results. We also looked at possible risks of communicating in this way. Our review found only one study evaluating the use of mobile phone messaging for communicating results of medical investigations. This study was at high risk of bias. The study suggested that the early communication of an antenatal screen test result by text messaging would not result in a difference in the anxiety scores of all pregnant women (irrespective of the test result) or when their test result is positive, however may reduce anxiety in pregnant women when their test result is negative. The usefulness of mobile phone messaging in other situations, or potential negative consequences, are not yet known.
The updated evidence is current to August 2015. We found only three appropriate studies with a total of 1158 participants to include. Data primarily came from one high-quality study with 1000 participants. Our analysis showed that in good grade patients, it remains possible that cooling the brain during surgery might prevent death or dependency in everyday activities. Very limited information was available for those without bleeding or those with poor grade bleeding. Unfavourable outcomes did not differ between participants with or without hypothermia. The quality of evidence for these outcomes remains unclear because they were reported in a variety of ways. We do not have enough data to be certain about the effect of cooling on death or dependency. The evidence for other outcomes was more uncertain, since we could not combine the data due to variation in the definition and reporting of outcome data. Data in our analyses were primarily from one high quality trial on good grade participants.
For the present review, researchers in The Cochrane Collaboration reviewed the evidence about the effects of gabapentin and two related drugs (pregabalin and gabapentin enacarbil) in adult patients (≥ 16 years of age) with 'episodic' migraine (headache on < 15 days per month). They examined research published up to 15 January 2013, along with three unpublished and previously confidential drug company research reports, and found six relevant studies, five of gabapentin and one of gabapentin enacarbil, both over a wide dose range. The studies showed that neither gabapentin nor gabapentin enacarbil was more effective than placebo at reducing the frequency of migraine headaches. Gabapentin commonly caused side effects, especially dizziness and somnolence (sleepiness). No studies of pregabalin were identified, and research on this drug is desirable.
We identified five studies including 523 participants that reported the diagnostic test accuracy of ultrasound. One of these studies, involving 262 participants, also reported the diagnostic test accuracy of serum bilirubin and serum alkaline phosphatase. All the studies included people with symptoms. One study included only participants who had not undergone previous cholecystectomy (removal of gallbladder). This information was not available from the remaining studies. Based on an average sensitivity of 73% for ultrasound, we would expect that on average 73 out of 100 people with common bile duct stones will be detected while the remaining 27 people will be missed and will not receive appropriate treatment. The average number of people with common bile duct stones detected using ultrasound may vary between 44 and 90 out of 100 people. Based on an average specificity of 91% for ultrasound, we would expect that on average 91 out of 100 people without common bile duct stones would be identified as not having common bile duct stones; 9 out of 100 would be false positives and not receive appropriate treatment. The average number of false positives could vary between 5 and 16 out of 100 people. Evidence from one study suggested that using a level of serum alkaline phosphatase higher than 125 units to distinguish between people who have and people who do not have common bile duct stones gave better diagnostic accuracy than using a level twice the normal limit (which usually ranges between 0 and 40). The study also showed better accuracy for serum alkaline phosphatase compared to serum bilirubin. The sensitivity of serum alkaline phosphatase at the 125 units cut-off was 92%, which means that 92 out of 100 people with common bile duct stones would be detected but 8 out of 100 people will be missed. The number detected could vary between 74 and 99 out of 100 people. Based on the specificity of 79%, 79 out of 100 people without common bile duct stones will be correctly identified as not having common bile duct stones while the remaining 21 people will be false positives. The number of false positives could vary between 16 and 26 out of 100 people. This suggests that further non-invasive tests may be useful to diagnose common bile duct stones prior to the use of invasive tests. All the studies were of low methodological quality, which may undermine the validity of our findings. Further studies of high methodological quality are necessary.
We included five studies involving 1350 people. We rated the quality of the evidence from studies as very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. There were problems with the design of some studies, and data were insufficient to answer some parts of our review question. The quality of the evidence from two studies was too low to allow us to draw any conclusions about the effects of the needles compared in the studies. However, there was sufficient evidence from the remaining three studies to allow us to reach conclusions. The three studies that allowed us to reach conclusions involved 1135 healthy infants aged mostly between two and six months. The infants were vaccinated in the thigh with either 25 G 25 mm (narrow, long needles), 23 G 25 mm (wide, long needles), or 25 G 16 mm needles (narrow, short needles). The needles were inserted at right angles (90° angle) into the skin and pushed down into the muscle of the thigh. The vaccines injected were combination vaccines designed to protect against several diseases including diphtheria (D), tetanus (T), whooping cough (pertussis), and Haemophilus influenzae type b disease (Hib). The vaccines all contained whole-cell pertussis (wP) vaccine antigens. These vaccines are commonly used in low- and middle-income countries but not in high-income countries. Our review findings are therefore most relevant to low- and middle-income countries. We found moderate-quality evidence that infants vaccinated in the thigh with 25 mm needles probably have fewer severe reactions (extensive redness and swelling in the thigh) after DTwP-Hib vaccination than infants vaccinated with 16 mm needles. We also found that the longer needles probably lead to fewer non-severe reactions such as mild swelling, tenderness, and redness after vaccination. The immune response to the vaccine is probably similar with the long and the short needles. We found low-quality evidence that the wide, long needle may slightly reduce the pain of the vaccination procedure compared with the narrow, long needle. We found moderate-quality evidence that the wide, long needle probably slightly reduces the duration of crying immediately following vaccination compared with the narrow, long needle. The differences in pain and crying between use of the wide and narrow needles are probably too small to be of any practical importance. We found low-quality evidence that infants vaccinated with the narrow, long needle may have slightly fewer non-severe reactions than infants vaccinated with the wide, long needle. We do not know if needle size has an effect on fever or other reactions that sometimes occur after vaccination including drowsiness, loss of appetite, and vomiting due to the very low quality of the evidence. The evidence in our review is current to October 2017.
We included 28 studies in which over 9000 children (aged 2 to 15 years) were randomised to treatment with fluoride gel or to a control group using placebo gel or receiving no treatment. Study duration ranged from 1 to 4 years (with 13 studies lasting around 2 years). Study reports were published between 1967 and 2005. Thirteen studies took place in the USA, seven in Europe, four in Brazil and one each in Canada, Israel, China and Venezuela. This review update confirmed that fluoride gel can reduce tooth decay in children and adolescents. We combined the results of 25 trials and found that on average there is a 28% reduction in decayed, missing and filled tooth surfaces (21% reduction in trials that used a placebo gel in the control group and 38% reduction in trials where the control group received no treatment) in permanent teeth. From the three trials looking at the effect of fluoride gel on first or baby teeth, the evidence suggests that using fluoride gel results in a 20% reduction in decayed, missing and filled tooth surfaces. We found little information about unwanted or harmful effects or how well children and young people were able to cope with the application of the gel. The application of fluoride gel results in a large reduction in tooth decay in both permanent and baby teeth. We found little information about potential unwanted or harmful effects from accidental swallowing of the gel during treatment. As children often swallow gel during application, more research is needed on these effects. The evidence available for permanent teeth is of moderate quality. The evidence on baby teeth is low quality because of the small number of studies available. The evidence available for adverse effects is very low quality.
We developed a comprehensive search strategy to search relevant scientific databases for clinical trials and found 13 trials that randomly assigned 605 high blood pressure patients to either fixed-dose partial agonist treatment or placebo for up to 12 weeks. On average, partial agonists lowered blood pressure by eight points in systolic and four points in diastolic pressure in patient with moderate to severe high blood pressure. We did not find any evidence showing that doses higher than the recommended starting doses would further lower blood pressure. On average, partial agonists lowered pulse pressure by 4 mmHg. The included studies generally did not report side effects serious enough that lead to termination of treatment. It was not clear whether partial agonists provide more side effects serious enough that lead to withdrawal compared to placebo. The quality of evidence is very low due to small sample size and high risk of bias.
In July 2018, we searched for clinical trials about exercise to reduce falls in adults living with and beyond cancer. We found 11 studies of variable quality and size, including a total of 835 people, that compared exercise to usual care. Most of the studies were very small, four with fewer than 30 people. Only one study reported on accidental falls. All 11 studies reported on one or more measures that are risk factors for falling (e.g. strength, flexibility and balance). We rated the quality of the evidence from the studies using four levels: very low, low, moderate or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The quality of the evidence was very low to low across all of the measures of interest. There were several weaknesses identified in the design of all studies including small numbers of participants. No study could prevent participants knowing their treatment and so there could have been bias. Only one study looked at the effect of exercise on accidental falls and found no difference in number of falls between people who exercised and people who did not (very low-quality evidence). Therefore, there were insufficient data for conclusions to be drawn regarding the effects of exercise on reducing accidental falls for people living with and beyond cancer. There was improvement in some factors that are known to affect falls; we found improvement in some measures of strength, flexibility and balance, although the overall quality of this evidence was very low to low.
The review authors identified two good quality controlled trials that randomized 287 children aged one day to 16 years to either a heparin-bonded catheter or a standard catheter. The median duration of time that the catheter could be used to give fluids (its patency) was not clearly different with the two types of catheter. This was seven days in the heparin-bonded catheter group and six days in the standard catheter group. There was a no difference between the two groups for risk of catheter-related thrombosis over the time the catheter was in. There was a trend towards a reduction in the risk of catheter occlusion in the first week after catheter placement, reported in one study only. The risks of catheter-related blood stream infections and bacterial colonization of the catheter were significantly reduced using the heparin-bonded catheter, with a longer time to develop infection (delayed in the heparin-bonded catheter group); however, it was reported in one study only and the strength of evidence was low. There was no significant difference in risk of thrombocytopenia after catheter placement.
This review summarises and discusses the available information on the use of beta-blockers in children with congestive heart failure. Seven studies, with a total of 420 children were included in the review. Beta-blocker therapy improved heart failure in four small studies with less than 30 participants each, and two larger studies with 80 participants each. However, the largest trial, with 161 participants, did not show a significant effect of the investigated beta-blocker over placebo. None of the studies reported any severe beta-blocker-related adverse events, apart from one child who had a heart rhythm disturbance. There were not enough data to recommend or discourage the use of beta-blockers in children with congestive heart failure. However, the current available data suggest that children with heart failure might benefit from beta-blocker treatment. Further investigations are required to establish guidelines for therapy.
This review found only two randomised studies of exercise in people with ALS. The trials compared an exercise program with usual care (stretching exercises). Combining the results from the two trials (43 participants), exercise produced a greater average improvement in function (measured using an ALS-specific measurement scale) than usual care. There were no other differences between the two groups. There were no reported adverse events due to exercise. The studies were too small to determine to what extent exercise for people with ALS is beneficial or whether exercise is harmful. We found no new trials when we updated the searches in 2012. More research is needed.
Although anticoagulants such as warfarin are of proven benefit in patients in certain subgroups of patients with heart failure, such as those with atrial fibrillation, there is little evidence that warfarin works well in the wider heart failure population. There may also be serious side effects such as bleeding (causing ulcers and haemorrhagic stroke). At present there are no data to recommend the routine use of anticoagulants to prevent thromboembolism in patients with heart failure who are in normal heart rhythm.
This review examined 16 randomised controlled trials of 15 different Chinese herbal medicines. The trials lasted from four weeks to two years (average nine months) and involved altogether 1391 participants. Death from any cause, diabetic complications and economic outcomes were not investigated. No serious adverse events were reported. The available evidence suggests that Chinese herbal medicines are able to lower and normalise high blood glucose. Due to considerable distortions (bias) in the trials, further high-quality and rigorously evaluated studies are required before any conclusions can confidently be reached about the effects of Chinese herbal medicines for the treatment of impaired glucose tolerance and the delay of diabetes onset.
In the present review we assessed the evidence for the efficacy, acceptability and tolerability of escitalopram in comparison with all other antidepressants in the acute-phase treatment of major depression. Twenty-two randomised controlled trials (about 4000 participants) were included in the present review. Escitalopram appears to be suitable as first-line antidepressant treatment for people with moderate to severe major depression. It has been compared with only a few other antidepressants and so we are unable to say whether it is better, worse or the same as many of the other drugs used in practice. However, it did perform better than citalopram when we brought together the results of six studies in nearly two thousand patients
We looked at the evidence up to February 2013 and found 1666 studies. We included eight studies in our review and seven studies (involving 772 patients) in our meta-analysis. The studies involved people who were in an unstable condition and critically ill. They were given one dose of etomidate or another sedative agent for endotracheal intubation. We reran the search in August 2014. We will deal with any studies of interest when we update the review. No strong evidence exists to suggest that etomidate, when compared to other bolus dose induction agents, increases mortality in critically ill patients. We must be careful in interpreting this finding because only large studies would be able to show a difference in mortality. So far, no such study has been completed. Etomidate does seem to impair adrenal gland functioning. Functioning is impaired most between four and six hours after etomidate is given. Sequential Organ Failure Assessment (SOFA) scores are used to find out how badly someone’s organs are failing. Using etomidate results in worse SOFA scores but this difference is small and not clinically meaningful. The effects of impaired adrenal gland functioning and higher SOFA scores on people’s health is unknown. Using etomidate does not seem to increase the length of time someone is in hospital (including an intensive care unit), the length of time a person is connected to a mechanical ventilator (a machine to assist with breathing), or the use of vasopressors (medicines to increase blood pressure). Most of the evidence was moderate quality. This is mainly because some small studies we looked at did not check up on people adequately after they were intubated. Most people that were involved in one study were intubated because they were in a coma. These people comprise 42% of those involved in the studies we looked at. People in a coma are unlike other critically ill people because they may not benefit to the same extent from having stable blood pressure during endotracheal intubation, which etomidate provides, nor are they at high risk from impaired adrenal gland function compared to other critically ill patients, for example those with severe infection.
We wanted to evaluate the effectiveness and safety of acupuncture for ASD by systematically reviewing all studies of acupuncture for ASD where people were randomly allocated to a treatment or control group (placebo, sham or no treatment), i.e. randomized controlled trials (RCTs). We searched through 15 databases, most recently in September 2010, and read over the titles and abstracts to make sure we identified everything relevant. We found10 RCTs to include in this review. These studies, which were carried out in Hong Kong, mainland China and Egypt, involved 390 children aged between three and 18 years. Two studies compared needle acupuncture with sham acupuncture and found no difference in core autistic features. Results did suggest that needle acupuncture might be associated with improvement in other areas of communication and linguistic ability, cognitive function and global functioning. Six studies compared needle acupuncture plus conventional treatment with conventional treatment alone. They used a range of tools to measure core autistic features and most could not show that acupuncture led to improvement in these. One trial did report, though, that needle acupuncture led to an improvement in scores on Autism Behavior Checklist. There was no evidence for improvement due to acupuncture on communication and linguistic ability but it might be beneficial for cognitive function and global functioning. Two studies compared acupressure plus conventional treatment with conventional treatment alone and found no difference in core autistic features, although acupressure seemed to improve some aspects of the secondary outcomes. Problems that were noted by parents of study participants included crying due to fear or pain, bleeding, sleep disturbance and increased hyperactivity. It is unclear if these were due to the acupuncture treatment. Half of the trials reported some negative effects but did not report how often or how severe these were and sometimes the problems occurred in both the treatment and control groups. None of the studies used measures of quality of life. Overall, acupuncture did not seem to be effective in improving core features of ASD but it might have improved certain developmental and functioning outcomes, at least in the short term. There are problems with assessing acupuncture due to the quality of the evidence. There were a small number of studies and they were all conducted with children. Moreover, there is a high likelihood that they may have been biased due to the methods used not being rigorous enough, the wide variety in the people and interventions in the studies, the inconsistent and imprecise reporting of results and the large number of analyses carried out, which make it more likely a significant result will be found just by chance. In conclusion, current evidence does not support the use of acupuncture for the treatment of ASD. We need high quality trials of larger size and longer follow-up as the evidence base at present has many limitations.
Our review included one published randomised controlled trial, involving 17,802 participants, which reported outcomes of VTE. This trial investigated rosuvastatin compared with placebo for the primary prevention of VTE. Analysis showed that, compared with placebo, rosuvastatin reduced the incidence of VTE and DVT, the risk of any (fatal and non-fatal) myocardial infarction, and any (fatal and non-fatal) stroke. There were no differences between rosuvastatin and placebo in the incidence of pulmonary embolism, fatal myocardial infarction, fatal stroke, and death after VTE. The incidence of any serious adverse events was not different between rosuvastatin and placebo. No firm conclusions or suggestions could be made from these findings. More randomised controlled trials of statins (including rosuvastatin) are needed to evaluate the efficacy of statins in the prevention of VTE. Quality of the evidence The quality of the evidence was moderate because of imprecision, as the required sample size for the outcomes of this review was not achieved.
The purpose of this review was to assess the risks and benefits of YF vaccine for people living with HIV. We found three cohort studies that addressed this question. One study in children, from a time before effective widespread use of antiretroviral drugs, found that YF vaccine worked much less well in children with HIV than it did in those without HIV. Two studies in adults found that the immune response to yellow fever vaccine was slightly lower in HIV-infected patients. No severe adverse events were observed in patients in these studies. However, because the numbers of people with HIV who have received YF vaccine is small, and serious side effects are uncommon in people without HIV infection, we are not positive about its safety. When it does need to be used, it should be given to people whose viral loads are low and CD4 counts are high.
This review aimed to assess the beneficial or harmful effects of chlorambucil for primary biliary cirrhosis. The authors identified only one randomised trial, with 24 participants included. This trial compared chlorambucil with no intervention. The trial is small and at a high risk of bias, which suggests that the results may not be reliable. Meta-analyses were not possible because of the inclusion of one trial only. Fisher's exact test and t-test were used instead. Chlorambucil was not associated with significantly lower mortality when compared with no intervention. All patients on chlorambucil experienced adverse events, especially bone marrow suppression. Chlorambucil led to a significant improvement in mean serum levels of bilirubin, albumin, immunoglobulin M, serum aspartate aminotransferase activity, and hepatic inflammatory infiltrates. However, these outcomes are unvalidated surrogate outcomes for patient-relevant outcomes. This means that improvement of these biochemistry measures cannot be taken as proof of improvement of patient-relevant outcomes. It remains unclear whether chlorambucil can be supported or rejected for use in patients with primary biliary cirrhosis.
As of August 2015, we identified 23 randomized controlled trials (RCTs: a type of scientific experiment in which people are randomly assigned to one of two or more treatments), which included 2675 children and adolescents between three years and 17 years of age. These studies compared amphetamines to placebo. Three different kinds of amphetamines were investigated: dexamphetamine, lisdexamphetamine and mixed amphetamine salts. The duration of the included studies ranged from 14 days to 365 days. The RCTs were conducted in the United States and Europe.Key resultsWe found that amphetamines were effective at improving the core symptoms of ADHD in the short term, but that they were also linked to a higher risk of experiencing adverse events such as sleep problems, decreased appetite, and stomach pain. We found no evidence that one kind of amphetamine was better than another, and found no difference between amphetamines that act for longer periods of time versus those that act for shorter periods of time. The quality of the included studies was low to very low because of problems in their design and large differences between the studies. Well-designed and clearly reported RCTs that are longer in duration are needed, so we may better understand the long-term effects (both positive and negative) of amphetamines.
This review therefore focused on the efficacy of influenza vaccination in children with cancer. We identified no studies that assessed the clinical efficacy of influenza vaccination; however, we identified one additional controlled clinical trial in our update, which brings the total to nine studies that assessed immune responses after vaccination in children with cancer. It was shown that children receiving chemotherapy mount poorer immune responses than healthy children, but that the vaccine can be safely administered. On the basis of this updated review, it is not possible to recommend or discourage influenza vaccination in children with cancer who are treated with chemotherapy. A future trial should address the clinical benefits of influenza vaccination in children with cancer who are treated with chemotherapy.
We found 11 randomised controlled trials on 1021 participants that compared inhaled hyperosmolar agents versus no mucolytic treatment. Five studies compared inhaled mannitol versus placebo (with a total of 883 participants) and two very small studies (with a total of just 25 participants) compared inhaled mannitol with no treatment. We also found four studies (with a total of 113 participants) that compared hypertonic saline with isotonic (normal) saline. For the comparison between mannitol and placebo only one study (a 12-month trial with 461 participants) provided information on the number of people who had an exacerbation (or flare up) over the course of a year. This study showed that people who were treated with mannitol had 8% fewer exacerbations on average compared with placebo. Overall, we felt the quality of this evidence was moderate and new trials would be likely to change either how effective we think the treatment is or how confident we are about it. Three trials assessed the effect of mannitol on health-related quality of life, and again the quality of the evidence was rated as moderate. An analysis of adverse events data, also based on moderate quality evidence, revealed no difference between mannitol and placebo The trials comparing hypertonic saline with isotonic saline had conflicting results for most of the outcomes of interest. Because we were unable to combine the data, it is not possible to draw robust conclusions for this comparison and judgments should be reserved until further data are available. Our analysis of adverse events between hypertonic saline versus isotonic saline showed no significant difference however this was based on a single study and the quality of the evidence was moderate. Details of how the patients in the trials were allocated to receive mannitol or not was clearly described in only one of the studies, and similarly only one of the hypertonic saline versus isotonic saline studies provided this information. The general lack of information on this point was considered carefully in the review in relation to our level of uncertainty in interpreting the results. Taking this into account, the quality of evidence was generally regarded as moderate both for the mannitol and hypertonic saline studies.
We included nine studies that compared the effectiveness of an intramuscular injection compared to corticosteroid tablets in patients presenting to an ED or similar acute care setting with acute asthma. The studies enrolled a total of 804 paediatric and adult participants. Most studies investigated the injectable corticosteroids dexamethasone or methylprednisolone compared to the corticosteroid tablets prednisone or methylprednisolone. Most studies did not report sources of funding (5 studies). Two studies received funding from general health research grants. One study was funded by a pharmaceutical company (Pfizer); however, reported that the company was not involved in any aspect of the study or manuscript preparation. One study reported being unfunded. Intramuscular injections of corticosteroids appear to be as effective as corticosteroids tablets in preventing relapse. We did not find any differences in the risk of relapse between participants receiving intramuscular injections and corticosteroid tablets. Although not all studies reported adverse effects in their study groups, we found no differences between participants receiving intramuscular injections and corticosteroid tablets. At follow-up, we found no differences in pulmonary function tests between participants who had received an intramuscular injection or corticosteroid tablets. In the studies that reported symptom scores and duration, we did not identify any differences between participants receiving corticosteroids by injection or by tablets. The quality of the evidence regarding the effectiveness of intramuscular injections of corticosteroids in improving health outcomes ranged from low to moderate. We had only moderate confidence about the estimated effects of intramuscular steroids on hospital admissions, improvement in respiratory function and relapse because of the risk of bias among included studies.
This systematic review aims to synthesize the evidence for use of STI as an alternative strategy in the management of chronic suppressed HIV infection. STI is a planned, experimental intervention, and the evidence from 33 available intervention trials has been summarized. Currently, several large STI trials are underway, investigating long-term effects of STI strategies. Their results will be available in a few years. Based on the studies we reviewed, we find that there is insufficient evidence to support the use of STI as a standard of care in the management of chronic suppressed HIV infection.
The review identified 102 relevant studies, 85 of which were on the use of music in hospital. Other environmental aspects considered were: aromas (two studies), audiovisual distractions (five studies), decoration (one study), air quality (three studies), bedroom type (one study), flooring (two studies), furniture and furnishings (one study), lighting (one study), temperature (one study), and multiple design changes (two studies). No studies meeting the inclusion criteria were found to evaluate: art, access to nature for example through hospital gardens, atriums, flowers, and plants, ceilings, interventions to reduce hospital noise, patient controls, technologies, way-finding aids, or the provision of windows. Overall, it appears that music in hospital may help improve patient-reported outcomes such as anxiety; however, there is less evidence to support the use of music for physiological outcomes (such as reducing heart rate and blood pressure) and for reducing the use of medications. For other aspects of hospital environments, there are not very many well designed studies to help with making evidence-based design decisions. The studies that have been included in this review show that physical changes made to 'improve' the hospital environment on the whole do no harm.
Twenty trials were included. These involved a total of 2562 mostly young active adult males. All trials had methodological flaws that could have affected their results. Data for pooling individual outcomes were only available for a maximum of 12 trials. Additionally, there was one low quality and potentially biased trial with very positive results in favour of surgery. When this trial was excluded, the findings of better results for surgery in terms of return to sports, re-injury, persistent pain and ankle instability as judged by the patient were no longer statistically significant. Thus, the trend to a better result from surgery remains unproven. Ankle stability, as judged by the clinician using standard tests, was better after surgery than with conservative treatment. Conversely, there was some limited evidence for longer recovery times, and higher incidences of ankle stiffness, impaired ankle mobility and complications in the surgical treatment group. We concluded that there was not enough evidence from randomised controlled trials to say whether surgery gives a better result than conservative treatment for acute ankle sprain in adults.
This review found 34 studies with 2657 people. It compared benzodiazepines when used alone as the only medication or when used in combination with another drug for people with schizophrenia. Information from the 34 studies was generally poor, incomplete and badly reported. The 34 studies were of short duration and were small in size. The review suggests that there is little evidence to support the use of benzodiazepines either alone or in combination. However, benzodiazepines do have sedative properties that can calm people down and help them become less agitated for short periods of time. More research, particularly involving benzodiazepines as add-on treatment used in combination with traditional antipsychotic drugs, is required. This plain language summary has been written by Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness, Email: [email protected]
The review assessed whether routine use of antibiotics at the time of an episiotomy prevented infection for women with an uncomplicated vaginal birth, compared with either placebo, or no antibiotics. We searched for evidence (24 July 2017) from randomised controlled trials in the medical literature. We only identified one small trial that was conducted in a public hospital in Brazil and provided very low-quality data from 73 women. The trial showed no clear difference between the groups, with or without antibiotics, of the number of women who experienced infection or breakdown of the episiotomy wound. No women developed infection of the lining of the uterus in either group. The trial did not report on any other outcomes of interest for this review. The current evidence on the impact of prophylactic antibiotics for prevention of infection after episiotomy is from one small trial with design limitations. The relatively low incidence of episiotomy infection, when infection control measures are well observed, raises questions about the potential added benefit of antibiotic prophylaxis, particularly when balanced against the risk of antibiotic-related side effects for the mother, and her baby, and in terms of emerging antibiotic resistance. There is a need for a careful and rigorous assessment of the comparative benefits and harms of prophylactic antibiotics on infection morbidity after episiotomy, in well-designed randomised controlled trials, using common antibiotics and regimens in current obstetric practice.
We included four studies in this review, which we included in the previous version of this review, which means that we did not identify any new relevant studies for inclusion in this update. The treatment comparisons were too dissimilar to be pooled and half of the studies were at high risk of bias. The quality of the evidence was very low for all outcomes. One study compared back school with a placebo (sham treatment) and found no difference between groups for pain at short-term follow-up. Concerning work status, people in the back school group had a significantly shorter duration of sick-leave than people in the placebo group at short-term follow-up. Four studies compared back school with another treatment (physical therapies, myofascial therapy, joint manipulations, advice). Overall, there were no differences between groups for pain, disability, work status and adverse events at any time of follow-up. Only one study showed that back school added to a back care programme was more effective than back school alone for disability at short-term follow-up. The included studies are insufficient to clearly answer our question and the inclusion of other well-designed studies is very likely to change the conclusions. However, back schools do not seem to be a treatment widely used nowadays for people with acute and subacute non-specific low-back pain and are not endorsed by guidelines. The quality of the evidence was very low for all the outcomes according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. This was due to poor study designs and imprecision in the results.
We found 37 studies (representing 6128 adults and adolescents). The people in these trials had mild to moderate asthma. Most (24) studies used the LTRA called montelukast, 11 studies used zafirlukast and only two studies used pranlukast. We divided all studies into three categories to help us make sense of the evidence. • Anti-leukotrienes and ICS versus same dose of ICS: Ten studies (representing 2364 adults and adolescents) contributed data for analysis. Anti-leukotrienes given with ICS reduced by half the number of patients with exacerbations requiring oral steroids (from 9% to 5% over three months), but we are unsure about effects of this treatment on quality of life or serious side effects. Anti-leukotrienes given with ICS improved lung function and asthma control measures. • Anti-leukotrienes and ICS versus higher dose of ICS: Eight studies (representing 2008 adults and adolescents) contributed data for analysis. Results showed no reduction in the number of patients with exacerbations requiring oral steroids and no difference in quality of life nor in side effects. Data showed no improvement in lung function nor in asthma control measures. • Anti-leukotrienes and gradual reduction of ICS dose versus gradual reduction of ICS dose alone: Seven studies (representing 1150 adults and adolescents) evaluated anti-leukotrienes given with a gradually reduced dose of ICS compared with a gradually reduced dose of ICS without use of anti-leukotriene agents. This approach was not beneficial for % reduction in the amount of ICS over time. More people receiving anti-leukotriene and ICS compared with ICS alone experienced increased serious side effects and showed no improvement in lung function nor in asthma control measures. For adolescents and adults with asthma not controlled with daily low-dose ICS, adding anti-leukotriene agents to ICS reduced by half the number of patients with asthma exacerbations requiring an oral corticosteroid. Anti-leukotrienes and ICS also improved lung function and asthma control. However, we are not sure whether the combination of anti-leukotrienes and ICS is superior to higher-dose ICS. Limited available evidence does not support use of anti-leukotrienes as a way to decrease ICS dose. In general, addition of anti-leukotrienes to ICS therapy was not associated with increased side effects, if the dose of ICS was maintained. Our confidence in the evidence was moderate or low for most outcomes.
Two trials assessed the effect of TXA in patients aged 16 and over. The largest (n = 20,211) involved patients suffering from a variety of types of trauma, and the other (n = 240) only those who had suffered traumatic brain injury. Results The trial assessing the effect of aprotinin was too small to provide reliable data. Results for TXA suggest that, when given early, TXA reduces the risk of death compared to patients who do not receive TXA without increasing the risk of side effects. However, there is still some uncertainty about the effect of TXA in patients who have bleeding inside the brain from a head injury, but are not bleeding from injuries elsewhere. It is possible that the effects of TXA are different in this specific patient group. We have found two ongoing trials that are trying to answer this question. The authors of this review conclude that TXA can safely reduce death in trauma patients with bleeding and should be given as soon as possible after injury. However, they cannot conclude whether or not TXA is also effective in patients with traumatic brain injury with no other trauma, until the ongoing trials have been completed. Quality of the evidence Evidence for important outcomes including mortality, need for further surgery and blood transfusion, came from high-quality evidence, meaning we have confidence in the findings. There was moderate-quality evidence for important adverse events including vascular occlusive events (including heart attacks, deep vein thrombosis, stroke and pulmonary embolism).
This review analyses the results from 13 clinical trials where 1923 eyes of 1135 participants were randomly treated with either LASIK or PRK. We considered the overall quality of evidence from these studies to be low. There was some evidence that LASIK gives a faster visual recovery than PRK, and is a less painful technique, although visual results one year after surgery were comparable. Surgical techniques are improving all the time and further trials are needed to see whether LASIK and PRK, as currently practised, are equally safe.
The search is up-to-date to 1 August 2017. We identified 14 clinical trials including 2966 men. We compared desmopressin alone or in combination with other medicines used for urinary problems (such as alpha-blockers or anticholinergics) against placebo (pretend treatment), behaviour changes, or medicines used for urinary problems alone or in combination. Most of the included studies enrolled only older men. Treatment with desmopressin for three to 12 months may reduce how often men urinate at night in a small number of men compared to placebo. Serious side effects were not increased. We do not know how the use of desmopressin compares to changes in behaviour. The effect of desmopressin on how often men urinate at night is likely to be similar to that of alpha-blockers when given for up to three months (i.e. short-term treatment) without major side effects. Adding desmopressin to an alpha-blocker seems to work little better than an alpha-blocker alone or an alpha-blocker combined with an anticholinergic. We rated the quality of the evidence to be low in most cases, meaning that we cannot fully trust the results. The included studies were poorly designed, small, and only followed people for a short time (usually three months or less).
We performed an extensive search for randomised trials comparing epinephrine alone versus epinephrine plus a second method. We found 19 clinical trials involving 2033 randomly assigned participants We found that adding a second procedure reduced the further bleeding rate and the need for emergency surgery, but the effect of this approach on death rates has not been proven. In conclusion, additional endoscopic treatment after epinephrine injection reduces further bleeding and the need for surgery in patients with high-risk bleeding peptic ulcer. Our risk of bias estimates show that the overall quality of the included studies was moderate or high. Although some studies had limitations in their design or implementation, most were clear about important quality criteria including randomisation and allocation concealment, sequence generation and blinding. We rated the quality of evidence as moderate for most outcomes. Further research is likely to have an impact on our confidence in the estimate of effect and may change the conclusions of this review.
This review identified 24 studies enrolling 2,610 patients comparing teicoplanin and vancomycin in those with either proven or suspected infection. Teicoplanin was as effective as vancomycin for treating infections caused by Staphylococcus aureus with similar results for clinical cure, microbiological cure and death. However, there were less adverse events (skin rash and red man syndrome) and it caused significantly less damage to the kidneys.
This review compares the standard treatment with a more invasive alternative, where pus-filled mass is drained by image-guided percutaneous procedure (performed through the skin). Seven low quality randomised trials were included. All the seven studies included a total of 310 patients, but due to selective outcome reporting bias, less patients could be included in our analyses. Pooled analysis of three homogenous trials showed that needle aspiration did not significantly increase the proportion of patients with fever resolution. Benefits could be observed in resolution time of pain and tenderness. No additional benefit has been found with percutaneous needle aspiration plus metronidazole versus metronidazole alone for uncomplicated amoebic liver abscesses in hastening clinical and radiologic resolution. However, this conclusion is based on trials with methodological flaws and with insufficient sample sizes, and requires further confirmation in larger well-designed, randomised trials.
In this review, treatments were divided into those with or without specific attention to handling depression. We found that smoking cessation treatments with specific attention to handling depression helped smokers who suffered from depression to quit. Psychosocial 'mood management' interventions, where participants learn how to handle depressive symptoms with psychological techniques, were effective in those with current depression and with a history of it. Bupropion, an antidepressant medication to help quit smoking, has been shown to be effective for smoking cessation in healthy smokers. Our findings show that bupropion may benefit smokers with a history of depression as well. However, this was not found for those with current depression. There was a lack of evidence for the effectiveness of other antidepressants to help smokers with a history of depression to quit. There was also not enough evidence for the use of antidepressants in smokers with current depression. Although treatments without specific attention to handling depression, such as nicotine replacement therapy and standard psychosocial smoking cessation interventions, have been shown to help other groups of people to quit smoking, there was not enough evidence to show that they were helpful in people with a history of or with current depression.
This review included 13 trials, which involved a total of 2498 older, usually female, patients who had undergone surgery for hip fracture. Generally the trials appeared well conducted, although some were at risk of bias that could affect the reliability of their results. For example, despite randomisation, in five trials there were some important differences in patient characteristics, such as age, at the start of the trial that could have influenced trial findings. The trial interventions were very varied but all compared multidisciplinary rehabilitation with usual care. In 11 trials, care was provided either totally or mainly in an inpatient or hospital setting. While there was a tendency for a better outcome after multidisciplinary rehabilitation, the results were not statistically significant and thus cannot be considered conclusive. However, the overall evidence indicates that multidisciplinary rehabilitation is not harmful. Additionally, there was some inconclusive evidence that multidisciplinary rehabilitation did not add to the burden of carers. In one trial that compared home-based multidisciplinary rehabilitation with usual inpatient care, carers reported significantly lower burden in the long term after multidisciplinary rehabilitation. Participants in the home-based rehabilitation group of this trial had shorter hospital stays, but longer periods of rehabilitation. One other trial found no significant effect from doubling the number of weekly contacts at the patient's home by a multidisciplinary rehabilitation team. Overall, the results of this review suggest that multidisciplinary rehabilitation may help more older people recover after a hip fracture. However, the results are not conclusive and more research is needed.
We found one relevant study that compared the effects of giving injections into the vein of two different lipid (fat) emulsions twice daily for 10 days: one emulsion (two or more liquids that are often unmixable) was derived from fish oil, and the other was derived from soya oil. Participants were followed for a total of 40 days. The study was conducted in Germany in 21 adults (18 men and 3 women) aged 21 to 65 years, with a mean of involved skin surface of 25%, who were in hospital with acute guttate psoriasis. The study was funded by the company that produces the oil emulsions. Treatments for which we found no evidence include phototherapy and topical, oral, and biological medicines. The only study identified did not measure our two primary outcomes: percentage of people treated whose skin became clear (or almost clear) of lesions; and the side effects, or harms, of the treatments. Most of our secondary outcomes were also not measured, including worsening of guttate psoriasis or recurrence within a period of six months after the treatment has finished; and percentage of participants achieving a Psoriasis Area Severity Index 75 or Physician's Global Assessment of 1 or 2. The included study did not report measuring any harms of the treatments; however, the study authors did report rare skin irritation at site of injection, but did not provide the number of affected participants. The study participants rated some outcomes themselves, including the appearance of the skin lesions, the effects on their daily life, itching, burning, and pain. After 10 days of treatment, study participants who received the fish oil-derived lipid emulsion (75% of people in this group) rated greater improvements than those receiving the soya oil-derived lipid emulsion (18% of people in this group). However, these results are uncertain as they are based on very low-quality evidence. The evidence is current to June 2018. We rated the quality of the available evidence as very low. We considered that the study may be at risk of bias due to limitations in its design, and only a small number of people were included in the study. In addition, the study only enrolled adults, although guttate psoriasis is more common in children.
. The review includes 11 studies investigating the use of GABA agonist drugs compared with placebo. All studies involved small numbers of participants (2 to 80 people) with schizophrenia or other chronic mental illnesses who had also developed antipsychotic-induced tardive dyskinesia. . Evidence of the effects of GABA agonist drugs in the treatment of tardive dyskinesia is not conclusive and not convincing. Any possible benefits of GABA agonist drugs are likely to be outweighed by the adverse effects associated with their use. . Evidence is weak, short term, small scale and poorly reported. It is not possible to recommend these drugs as a treatment for tardive dyskinesia. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (http://mcpin.org/).
Many people with schizophrenia experience periods of illness followed by relatively stable periods (although symptoms of illness such as hearing voices and seeing things often remain in the background). This means that many people with schizophrenia may become unwell again and need to go back into hospital. Training in early warning signs techniques encourages people to learn, detect and recognise the early warning signs of future illness. Studies indicate that noticing even small changes in signs and symptoms of schizophrenia can often predict future illness and relapse two to 10 weeks later. Early warning training may help to prevent or delay relapse, so reducing the chances of going into hospital. Recognition of early warning signs requires detailed history taking, sometimes with additional techniques such as diary keeping, completion of questionnaires and a plan of action based on anticipated early warning signs. Training can be undertaken by the individual or be group-based, involving health professionals, family members or carers. Successful training seems to require around 12 sessions and involves therapists of high competency.   This review includes a total of 34 studies. It found that there are positive benefits of training in early warning signs. It reduces rates of relapse and re-hospitalisation (but not on time to recurrence). It should be noted that training in early warning signs was mainly used alongside other psychological therapies, so it is not entirely clear what proportion of the positive effect is due to training in early warning signs alone. Moreover, the overall quality of the evidence from these studies was judged to be very low. This means that we do not know if interventions using early warning signs, with or without additional psychological treatments, will have the same beneficial effects outside clinical trials.   Further research is required to decide whether training in early warning signs is effective on its own. Effects on quality of life, satisfaction with care, money spent, and burden of care for carers are unclear, so ideally should be known before training programmes are put into wider use. At this time, there is not enough evidence to support training in early warning signs alone. This plain language summary was written by consumer, Ben Gray of RETHINK.
We found three randomized controlled trials involving 2081 participants. No outcome data were available for one included study. The design of the other two RCTs was generally good, although there were some weaknesses. The majority of participants were included in centres around North America. The evidence is current to October 2014. Both RCTs were funded but stated that the sponsors contributed only to the study design and did not participate in the conduct of the study. We found that silver-coated ETT reduced the risk for developing VAP from 6.7% to 3.5% within 10 days of intubation compared with non-coated ETT in people who required mechanical ventilation for 24 hours of longer, although the quality of evidence for this outcome was low. One study showed that an initial VAP occurrence appeared much later in time in people who had a silver-coated ETT compared with a non-coated ETT, although again the evidence was low quality. We could not draw conclusions about hospital mortality, device-related complications, duration of intubation, and length of hospital and intensive care unit stay owing to uncertainty of the effects. We found no clinical studies evaluating the cost-effectiveness of silver-coated ETTs. The overall quality of evidence was low for all interested outcomes mentioned. Limited evidence suggests that silver-coated ETT seems to be an effective device in reducing the risk of VAP, although data for our other key outcome of hospital mortality were inconclusive. Larger studies with more participants who are at risk for VAP and who require mechanical ventilation for a longer period of time are needed.
This review involved searching the literature for well-conducted (randomised) studies that compared ECT to both simulated ECT and to antidepressants. The review found only four studies, all of which had serious problems in their methods. At present, therefore, it is not possible to draw firm conclusions on whether ECT is more effective than antidepressants,.or on the safety or side effects of ECT in elderly people with depression.
Studies on psychosocial interventions for mental disorders such as schizophrenia and anxiety show that they are effective treatments. Reports in the literature suggest that they may be useful for people with bipolar disorder as well. The role of the family is important in the care of people with bipolar disorder, with effective family functioning helping to maintain a person's psychological balance. This systematic review investigated the effectiveness of any psychosocial family intervention for people with bipolar disorder and/or their families and carers. Seven randomised controlled trials (393 participants) were included in the review, all of which evaluated psychoeducational interventions. Five studies compared family interventions against no treatment, and three studies compared one type or delivery of family intervention against another family intervention. Differences in the interventions, outcome measures and end points used in the trials did not allow us to perform a meta-analysis. Whilst results from individual studies did not suggest a significant effect for family interventions when added to drug therapy, the studies provide insufficient evidence to draw conclusions which can be generalised to everyday practice. Further research using appropriate randomised controlled trial methodology and evaluating family interventions other than psychoeducation is called for in this under-researched and important topic.
This systematic review identified six trials which included 937 participants with macular oedema secondary to CRVO (as of 29 October 2013). The trials compared sham injections with one of four types of anti-VEGF agents: aflibercept (VEGF Trap-Eye, Eylea), bevacizumab (Avastin), pegaptanib sodium (Macugen) and ranibizumab (Lucentis). All trials treated participants for at least six months. Three trials were multicentre, international trials and three were conducted in Norway, Sweden or the USA. Overall, treatment with anti-VEGF agents increased the chance of a significant gain in vision (at least 3 lines on the vision chart) at six months by more than two and a half times, compared to no treatment. Furthermore, the risk of losing significant vision (at least 3 lines on the vision chart) was reduced by 80% in those receiving anti-VEGF therapy compared to those receiving no treatment. No significant safety concerns were identified at six or 12 months, but the available studies do not allow a conclusion about their long-term effectiveness and safety to be drawn. Nevertheless, the availability of anti-VEGF treatment for CRVO macular oedema represents an important advance in the clinical management options for this sight-threatening disease. The six trials included in this review were high quality and consistently demonstrated visual benefit from anti-VEGF injections.
We included six randomised trials (studies in which participants are allocated at random (by chance) to receive one of the treatments being compared). These trials included 698 people and tested three different types of psychotherapy. All studies looked at whether adding psychotherapy to current medical treatment leads to improvement in depression. All studies were funded by public research grants. We found that patients who receive psychotherapy as well as usual care with antidepressants had fewer depressive symptoms and were more often depression-free six months later compared with patients who continued with usual care alone. We are moderately confident of these findings, which means that the true effect of adding CBT may be different from what we found, although findings are likely to be close. We also found that added psychotherapy was as acceptable to patients as usual care alone. Two studies noted similar beneficial effects after 12 months, and one study at 46 months. Two studies reported harmful effects in people receiving usual care alone (one suicide, two people hospitalised) but none in people receiving psychotherapy in addition to usual care. Because participants were aware of the treatment they had received, and because we identified only a small number of studies, we graded the evidence as moderate in quality for findings at six months and low in quality for long-term results. This assessment might change in the future, if higher-quality research results become available.
This systematic review focused on (randomised) controlled studies. We could not identify any randomised controlled trials (RCTs), quasi-randomised trials or controlled clinical trials (CCTs) in which the only difference between the intervention and control group was the use of intracystic bleomycin. However, we did identify one RCT comparing intracystic bleomycin with intracystic phosphorus32 (32P), which is a radioactive isotope of phosphorous used for intracystic irradiation. Only seven children were included in this study. The study has a high risk of bias and the sample size is too small to detect a difference in outcomes. The therapeutic use of intracystic bleomycin in children with cystic craniopharyngiomas currently remains uncertain. Although there was no significant difference in total adverse effects between the two treatment groups, there was a significant difference in both headache and vomiting in favour of the 32P group. The quality of the evidence is, however, very low. More high-quality studies are needed but will be difficult as so few children get these tumours.
Our review identified and subsequently included five relevant randomised controlled trials. A total of 373 subjects were analysed. A meta-analysis was performed to pool available data from individual trials. Our results found that patients with G. lucidum extract in their anticancer regimen were 1.27 times more likely to respond to chemotherapy or radiotherapy than those without. However, the data failed to demonstrate significant effect on tumour shrinkage when it was used alone. In addition, G. lucidum could stimulate host immune functions by considerably increasing CD3, CD4 and CD8 lymphocyte percentages. Nevertheless, natural killer (NK)-cell activity, which has been suggested to be an indicator of self-defence against tumour cell, was marginally elevated. Patients in the G. lucidum group were found to have a relatively better quality of life after treatment than those in the control group. A few cases of minor side effect associated with G. lucidum treatment including nausea and insomnia were reported. There are limitations of the results from this systematic review. First, most included studies were small and there were concerns on the methodological quality of individual trials. Second, all participants in the individual trials were recruited from the Chinese population. Together, the robustness and applicability of the results were largely affected.
Steroid drugs have been effective in improving lung function but early use is associated with an increase in adverse effects (see Early Review). The review of trials found that moderately early use of corticosteroids (started at 7-14 days) reduces the risk of developing CLD. There is limited evidence about possible long term harmful effects. Short term adverse effects include high blood pressure, infection and an excess of glucose in the blood of these preterm babies. More research is needed. Steroid use should be limited until more information is available.
. A search for randomised trials investigating psychoeducation for the siblings of people with severe mental illness was run in 2013. Results of the search suggest that brothers and sisters form a small proportion of family members participating in studies of this kind. Only one study meeting the review criteria was found. This study included nine siblings and compared a psychoeducational intervention with standard care in a community care setting, over a period of 21 months. . Better outcomes in terms of coping were identified for those siblings who received psychoeducation. However, the number of participants was small and the quality of evidence low, and there is no conclusive evidence that psychoeducation is of benefit for brothers/sisters in this and other important areas (such as wellbeing, quality of life) or for the outcomes of people with mental illness (such as mental state, hospital admission or length of hospital stay). . Further studies are needed to understand the role of psychoeducation in specifically helping brothers and/or sisters to cope with providing care for their mentally ill siblings. The scarcity of good quality studies means that it is not possible to assess which type of psychoeducation is the most effective, although interventions using a group format that brings many family members together to receive education and share their experiences seem well-received by the participants. This plain language summary has been written by a consumer: Ben Gray, Senior Peer Researcher, McPin Foundation.http://mcpin.org/
We found four relevant studies, but one was withdrawn before anyone was signed up. The other three compared a LAMA called tiotropium Respimat to placebo for around a year, with participants in both groups continuing to take their usual LABA/ICS inhaler. People generally had quite poor lung function when they entered the studies, suggesting their asthma was not well controlled - in respiratory medicine, this is known as 'severe asthma'. Over 48 weeks, 328 out of 1000 people taking their usual LABA/ICS had to take a course of oral steroids compared with 271 if they took tiotropium as well. However, uncertainty in the results meant that rather than there being 271 people taking oral steroids, there could be anywhere from 218 to 333 people per 1000 who would have to take oral steroids, so we couldn't be sure of the benefit. Quality of life scores were not that different between those who took tiotropium and those who didn't. The studies showed different results for whether people taking tiotropium were more likely to suffer a serious side effect, but fewer people had non-serious side effects if they took tiotropium. We couldn't tell whether taking tiotropium on top of LABA/ICS reduced the number of people who had to go to hospital for an asthma attack because it didn't happen often enough for us to have confidence in the result. There was high quality evidence that showed benefits to lung function and probably small benefits on measures of asthma control.
This review contained 14 trials (with 590 participants) and tested the effectiveness of tricyclic drugs against placebo. Trial data were available for amitriptyline, desipramine, imipramine and nortriptyline. Based on nine trials (454 participants), there was no evidence that tricyclic drugs lead to higher rates of remission or response than placebo. Based on 13 of the trials (533 participants), there was evidence that people treated with a tricyclic drug had lower depression severity scores than those on placebo, however, the size of this difference was small. Consistent with their known mechanism of action, tricyclic drugs were more likely than placebo to cause vertigo, symptoms of lowered blood pressure, tremor and dry mouth. Subgroup analyses of six trials involving only adolescents (239 participants) and two trials involving only children (77 participants) found no evidence of differential rates of remission or response between the age groups. In contrast, there was lowering of depression scores in eight trials involving only adolescents (414 participants) and no lowering of depression scores in three trials involving only children (64 participants). Most of the included studies were conducted in the era before standard methods for conducting treatment trials for depression in children and adolescents came about. There were considerable differences between the studies with regards to the clinical tools and methods used in assessment of improvement. Most trials were small. Only two trials produced a definitive result for depressive symptoms, and no trial produced a definitive result for response or remission. There was typically insufficient information to judge the quality of the trials accurately. With these limitations, it is difficult to answer questions about the effectiveness and safety of tricyclic drugs for treating depression in children and adolescents. Current evidence suggests that the situation is much the same for newer-generation antidepressants. Clinicians need to provide accurate information to children and adolescents, and their families, about the uncertainties regarding the benefits and risks of antidepressants as a treatment option for depression. Tricyclic drugs do not seem useful for treating children before puberty, and are, at most, of moderate benefit for adolescents.
Study characteristics: We identified 15 eligible trials enrolling a total of 1690 infants. These trials were generally of good quality. Key findings: The overall analysis showed a reduction in the risk of severe fungal infection in infants who received systemic antifungal prophylaxis but did not show a difference in the risk of death. The trials did not assess the risk of long-term problems, including disabilities. Conclusions: There is evidence from some good-quality trials that giving infants an antifungal drug regularly for the first four to six weeks after birth reduces the number of infants who develop severe infection. There is not yet any convincing evidence that death or disability rates are affected.
Despite the critical importance of knowing whether surgery is beneficial, only three trials directly compared discectomy with non-surgical approaches. These provide suggestive rather than conclusive results. Overall, surgical discectomy for carefully selected patients with sciatica due to a prolapsed lumbar disc appears to provide faster relief from the acute attack than non-surgical management. However, any positive or negative effects on the lifetime natural history of the underlying disc disease are unclear. Microdiscectomy gives broadly comparable results to standard discectomy. There is insufficient evidence on other surgical techniques to draw firm conclusions. Trials showed that discectomy produced better outcomes than chemonucleolysis, which in turn was better than placebo. For various reasons including concerns about safety, chemonucleolysis is not commonly used today to treat prolapsed disc. Many trials provided limited information on complications, but generally included recurrence of symptoms, need for additional surgery and allergic reactions (chemonucleolysis). Many of the trials had major design weaknesses that introduced considerable potential for bias. Therefore, the conclusions of this review should be read with caution. Future trials should be designed to reduce potential bias. Future research should explore the optimal timing of surgery, patient-centred outcomes, costs and cost-effectiveness of treatment options, and longer-term results over a lifetime perspective.
The primary objective of this review was to assess the relative effectiveness of oral versus intra-vaginal anti-fungals for the treatment of uncomplicated vulvovaginal candidiasis. The secondary objectives of the review were to assess the cost-effectiveness, safety and patient preference of oral versus intra-vaginal anti-fungals. No statistically significant differences were observed in clinical cure rates of anti-fungals administered by the oral and intra-vaginal routes for the treatment of uncomplicated vaginal candidiasis. No definitive conclusion can be made regarding the relative safety of oral and intra-vaginal anti-fungals for uncomplicated vaginal candidiasis. The decision to prescribe or recommend the purchase of an anti-fungal for oral or intra-vaginal administration should take into consideration: safety, cost and treatment preference. Unless there is a previous history of adverse reaction to one route of administration or contraindications, women who are purchasing their own treatment should be given full information about the characteristics and costs of treatment to make their own decision. If health services are paying the treatment cost, decision-makers should consider whether the higher cost of some oral anti-fungals is worth the gain in convenience, if this is the patient's preference.
This Cochrane review summarizes evidence from forty-eight randomised controlled trials evaluating the effectiveness and safety of anticonvulsants in the treatment of alcohol withdrawal symptoms. There are limited data comparing anticonvulsants versus placebo and no clear differences between anticonvulsants and other drugs in the rates of therapeutic success. Data on safety outcomes are sparse and fragmented. There is a need for larger, well-designed studies in this field.
On 8 May 2013, we performed searches to look for clinical trials on the use of topiramate to treat neuropathic pain or fibromyalgia. We found four studies of reasonable quality that tested topiramate against placebo for a number of weeks. Almost all of the 1684 people in the studies had painful limbs because of damaged nerves caused by diabetes. Topiramate did not help the pain and was no different from placebo except in causing more side-effects, which made many more people withdraw from the studies early. About 3 people in 10 withdrew because of side-effects with topiramate compared with 1 in 10 with placebo. Topiramate has not been shown to work as a pain medicine in diabetic neuropathy.
Only two randomised studies, totaling 104 participants, were found that compared rehabilitation programmes for this condition. This means that many proposed techniques have not been subjected to proper scrutiny. There is limited evidence from one study to suggest that rate of recovery can be increased with an increased daily frequency of hamstring stretching exercises. There is preliminary evidence from another small study of mixed ability athletes to suggest that exercise to correct movement dysfunction could reduce time to return to full activity and the risk of re-injury. Further studies are required to check these findings and to inform on current practice and the widely published rehabilitation protocols for these injuries.
This is an update of a previous review, which found only one randomised trial of 62 adults, suggesting that IVIG is not useful in myocarditis. A second trial was added with this update. This trial evaluated 83 children who had the relatively rare combination of myocarditis and encephalitis (inflammation of the brain). Investigators found a lower death rate among children receiving IVIG than in those who did not, but this study had high risk of bias. More study is required before IVIG can be routinely recommended for adults or children with myocarditis.
We found 10 randomised controlled studies (studies where schools were assigned to receive FAST or to continue as usual, by a procedure similar to tossing a coin), with a total of more than 9000 children and their families. Nine of the studies took place in the USA and were funded by agencies in the US federal government. One study took place in the UK. Children's ages ranged from five to nine years, and most of the USA-based children were members of a racial or ethnic minority group. Boys and girls were represented at approximately equal rates. In most studies, FAST was delivered at children's schools after the end of the school day, although in some studies it was delivered outside of school (e.g. at a community centre). The trials lasted about eight weeks and usually examined the effects of FAST compared to no additional intervention. The evidence is current as of December 2018. A meta-analysis is a statistical method of combining data from several studies to reach a single, more robust conclusion. We were able to use data from nine studies in a meta-analysis measuring the impact of FAST for children aged between five and eight years. Although individual studies reported some positive findings, there was little evidence to suggest that being involved in a FAST programme results in important improvements in the primary outcomes of child school performance, parental substance abuse, or parental stress. No study measured child adverse outcomes. Furthermore, there was little evidence to suggest that FAST leads to important improvements in child behaviour or family relations. We judged the certainty of evidence in the included studies for the main review outcomes to be moderate or low risk. Failure to include all families in outcome analyses (attrition) and possible bias in recruitment of families into the trials were the main limitations in the evidence. Evidence on the effectiveness of being assigned to FAST is of moderate to low certainty and does not suggest that being assigned to FAST confers important benefits for students and their families.
We searched for studies that investigated the effects of speed of injection on the amount of pain and bruising where the injection is given (current to March 2017) and found four studies that fitted our review criteria. These studies took place in Turkey, Italy, and China. They enrolled a total of 459 people including 287 female and 172 male participants. All patients received LMWH, and none of the studies used UFH. Participants were treated in hospital, in neurology, orthopaedic, and cardiology units. Investigators injected heparin slow or fast into the abdomen (stomach) of participants. Participants could watch the injection being given and knew whether it was fast (10 seconds long) or slow (30 seconds long). Participants given injections said that pain was less with the slow injection after 48 hours. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 hours and 72 hours after injection. The bruise was not smaller with the slow injection. None of the included studies reported if participants had a swelling with blood inside (haematoma). We graded the quality of evidence as low because we found only a small number of published studies that reported on this question. These studies were small and had contradictory results. The fact that participants knew whether they received a fast or a slow injection may have affected the results.
The effect appeared to be greater in trials including a high proportion of patients with early stage disease. Combined chemotherapy/radiotherapy also delayed tumour recurrence and reduced the risk of re-growth near the original cancer site as well as in other parts of the body. There was an increase in side-effects, principally affecting the blood and bowel, but these generally only lasted a short time. Long-term effects were poorly reported.
In other Cochrane reviews, alarms triggered by wetting, desmopressin and tricyclic drugs have been shown to work during treatment. However, alarms have a more sustained effect than desmopressin and tricyclics after treatment has finished. The adverse effects of alarm therapy (tiredness and waking other members of the family) are relatively benign and self limiting compared with the adverse effects of drugs. One class of drugs (anticholinergic drugs) appears to improve the efficacy of other established treatments such as tricyclics, bedwetting alarms and desmopressin. The cost of treating children with bedwetting with alarm therapy or drugs may vary in different countries.
This review of eight studies, involving 1338 low-risk women in the first stage of spontaneous labour at term, showed that oxytocin did not reduce the need for caesarean sections. Neither did it reduce the need for forceps deliveries or increase the number of normal deliveries when compared with no treatment or delayed oxytocin treatment. Oxytocin seemed to shorten labour by nearly two hours on average. The uptake of epidurals was no different. It does not seem to cause harm to the mother or baby, but the sample size was too small to determine if its use has an effect on the death rates of babies. The decision whether to undergo this treatment is one that can reasonably be left to women to decide in the context of a reduction in the length of labour. The included trials used different doses of oxytocin, and different criteria for starting treatment in the delayed oxytocin arm.
We found only one small randomised controlled trial (including 210 very low birth weight newborn infants) that addressed this question. This trial did not show that early planned removal of UVCs from infants could reduce their chance of developing a bloodstream infection. However, because the trial was small, this finding is not certain. The trial did not provide sufficient evidence to inform policy or practice; larger trials are needed to resolve this question fully.
We found 29 new randomized trials (up to June 2010), bringing the total of studies included in the review to 43. In most of the studies, training interventions were directed at primary care physicians (general practitioners, internists, paediatricians or family doctors) or nurses practising in community or hospital outpatient settings. Some studies trained specialists. Patients were predominantly adults with general medical problems, though two studies included children with asthma. These studies showed that training providers to improve their ability to share control with patients about topics and decisions addressed in consultations are largely successful in teaching providers new skills. Short-term training (less than 10 hours) is as successful in this regard as longer training. Results are mixed about whether patients are more satisfied when providers practice these skills. The impact on general health is also mixed, although the limited data that could be pooled showed small positive effects on health status. Patients' specific health behaviours show improvement in the small number of studies where interventions use provider training combined with condition-specific educational materials and/or training for patients, such as teaching question-asking during the consultation or medication-taking after the consultation. However, the number of studies is too small to determine which elements of these multi-faceted studies are essential in helping patients change their healthcare behaviours.
The aim of this systematic review is to outline the possible benefits (i.e. prolonging survival) and also the disadvantages (adverse events) of therapy with interferon-alpha, administered alone or in combination with other proven drug regimens (otherwise known as chemotherapy) to patients affected by follicular non-Hodgkin's lymphoma. Interferons are proteins secreted by vertebrate cells that exhibit various biological actions. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, augment natural killer cell activity, and show several other immunomodulatory functions. Interferons, types alfa-2a or alfa-2b, are usually administered in combination with other drugs to treat a variety of infective and neoplastic diseases. The results showed a significant benefit in progression-free survival in patients treated with interferon-alpha alone or combined with chemotherapy as compared with comparator therapies. There was, however, less evidence that interferon-alpha supported any benefit on overall survival. Furthermore, the presence of relevant drug-related adverse events suggested that a careful analysis of the risks and benefits has to be performed when making a specific clinical decision about this therapy.
A literature search conducted in October 2013 resulted in 12 randomised controlled studies with 2317 patients that could be included in the analysis. The patients had metastatic breast cancer and either they had not been treated or had received one or two treatments after their diagnosis of metastatic breast cancer. The primary outcomes were overall survival and progression-free survival (time from randomisation to the time of disease progression). Secondarily, we compared the degree the tumour shrunk in response to chemotherapy (overall response rate), toxicity and quality of life. There was no difference in overall survival between the two groups but we found that when drugs were given one at a time there maybe more time before the tumours grew back again (longer progression-free survival). However, combination chemotherapy caused tumours to shrink more, although this did not result in longer survival than when using sequential chemotherapy. Rates of febrile neutropenia (infection) were higher in the combination arm but there was no difference in the rates of neutropenia (low white blood cells). There was no difference in quality of life between the two groups but there were only three trials that reported this information. Quality of life should be included as an outcome in future trials addressing this question. Overall, the studies did not consistently report the way patients were randomised and this may be a source of bias in the results. Generally this review supports the recommendations by international guidelines to use sequential monotherapy unless there is rapid disease progression.
We found three studies (including 1713 participants) that fulfilled the review selection criteria. All studies compared alemtuzumab versus subcutaneous interferon beta-1a for people with relapsing–remitting MS. In two of the studies (CARE-MS and CAMMS223) the participants were being treated for the first time (treatment-naive). The third study (CARE-MS II) included participants with at least one relapse while being treated with interferon beta or glatiramer acetate for at least six months. The review of these comparative studies found that, compared to subcutaneous interferon beta-1a, alemtuzumab reduces the risk of relapse, improves function and seems not to increase the overall risk of adverse events. Additionally, alemtuzumab reduces the risk of new or enlarging lesions of MS detected using magnetic resonance imaging (MRI). However, there is a lack of information about the effects of alemtuzumab on several patient-related outcomes such as (a) quality of life, (b) the rate of each adverse events (separately) and (c) the frequency of long-term adverse events and serious adverse events. The overall methodological quality of the included studies was moderate to high. However, because of the small number of included studies and the low rate of events, we judged the overall quality of the evidence for the main outcomes as very low to moderate. This means that new studies are likely to have an important impact on our confidence in the estimate of effect and may change the estimate or that we are very uncertain about the estimate.
In December 2018 we searched for high-quality studies (randomly dividing participants into different treatment groups) investigating treatments for poisoning that laypeople can perform. We found 24 studies with 7099 participants. All but one study took place in hospitals; the remaining one was in a home setting. Fourteen studies either did not specify the type of poison or studied different kinds. The others investigated overdoses of specific medicines (paracetamol, carbamazepine, antidepressant, benzodiazepine) or poisonous plants (yellow oleander or poisonous berries). Twenty-one trials studied different treatments with activated charcoal: as a single dose or multiple doses, with or without other first aid treatments (a substance to speed up bowel transit), and with or without hospital treatments. Six studies compared syrup of ipecac, with or without other first aid treatments (single-dose activated charcoal plus bowel transit enhancing substance) versus no treatment. We found no studies that investigated the neutralization or dilution of the poison or the use of certain body positions. Two studies compared a single dose of activated charcoal to no treatment following poisoning with paracetamol or different kinds of poisoning. We are uncertain about the treatment's side effects, admission to intensive care or worsening of the patient, and there was no information about effects on death, symptom duration, poison uptake or hospitalization. One study compared a single dose of activated charcoal to ipecac in mixed types of poisoning. We are uncertain about the effect of activated charcoal compared to ipecac, on the patient's level of coma or the number of unwanted effects. There was no information about effects on death, symptom duration, poison uptake, hospitalization or intensive care admission. One study compared ipecac to no treatment in children who ate poisonous berries at home. There may be an increase in the number of unwanted effects for ipecac. There was no information about effects on death, poisoning symptoms, symptoms duration, poison uptake, hospitalization or intensive care admission. We also investigated the use of single-dose or multi-dose activated charcoal, with or without hospital treatment, compared to each other or no treatment. Furthermore, we investigated the added value of ipecac to single-dose activated charcoal and the added value of adding bowel transit enhancing substances to AC. All but one study took place in a hospital setting, which means that the results cannot be directly applied to the lay setting. Because studies did not always report the methods they used, we are uncertain about the quality of the research conduct for many. Outcomes important to patients and pre-specified by us as important outcomes for this review were often absent or incompletely reported. Our certainty about the results of this review is mostly low to very low. Therefore future research is highly likely to change the findings. Based on the identified evidence, we cannot draw any conclusions about the effects of any of the investigated first aid treatments in a lay setting.
Analysis of nine trials does not suggest that this practice increases the risk of a severe bowel disorder called 'necrotising enterocolitis'. Further trials could provide more robust evidence to inform this key area of care.
Results showed that studies evaluating oral drinks with added nutrients to assist fighting infections ('immune enhancing') given before an operation could reduce total complications from 42% in the control group to 27% in those who received the drinks, while infections were reduced from 27% in the control group to 14% in the group given the drinks. Parenteral nutrition reduced total complications from 45% in the control group to 28% in the group receiving parenteral nutrition. There were no benefits demonstrated for either enteral or standard supplement drinks. Thus, some benefits have been demonstrated from giving nutritional support to patients before an operation with immune enhancing drinks and with parenteral nutrition. However, studies on parenteral nutrition were over 20 years old and during that time there have been many changes to surgical practice. Quality assessment of studies on PN was generally low. Immune enhancing drinks have only been tested with selected surgical patients and some unwanted effects have also been reported using these drinks in critical care patients; it is therefore unknown whether there would be detrimental effects by giving these drinks to patients who could potentially require critical care support after their surgery. No benefit of standard oral or enteral feeding was demonstrated and more research is required in these areas with malnourished patients.
We included 51 studies that analysed a total of 5345 participants. The evidence in this review is up to date as of 28 September 2016. Generally study participants were children and adults who had gingivitis or periodontitis, were able to use usual tooth cleaning methods and were healthy. We did not exclude studies where some or all participants had medical conditions or special care needs as we considered the use of mouthrinses with chlorhexidine to be particularly relevant to them. The included studies assessed the effects of chlorhexidine mouthrinse used for at least 4 weeks in addition to conventional tooth cleaning on gingivitis in children and adults. There is high-quality evidence that the use of mouthrinses containing chlorhexidine in addition to usual toothbrushing and cleaning for 4 to 6 weeks or 6 months leads to a large reduction in the build-up of plaque. There is also high-quality evidence of a moderate reduction in gingivitis in people with a mild level of it, although because the level of disease was already low this is not considered clinically important. The nature of the available evidence does not allow us to determine the level of reduction of gingivitis in people with moderate to severe levels of it. There was no evidence that one concentration or strength of chlorhexidine rinse was more effective than another. Rinsing for 4 weeks or longer causes tooth staining, which requires scaling and polishing carried out by a dental professional. Other side effects have been reported, including build-up of calculus (tartar), temporary taste disturbance and temporary shedding of/damage to the lining of the mouth. One study was assessed as being at unclear risk of bias, with the remaining 50 being at high risk of bias, however this did not affect the quality assessments for gingivitis and plaque as we believe that further research is very unlikely to change our confidence in the estimate of effect.
We searched medical databases for studies in which participants were randomly assigned to dimethyl fumarate or a control drug (randomised controlled trials). The efficacy of this therapy was considered in terms of occurrence of relapses and progression of the disease. We found moderate quality evidence that both dosages of dimethyl fumarate reduce the number of people with RRMS having relapse after two years of treatment, while there is low quality evidence showing that the medicine reduces the number of people who experience worsening disability at the end of two years.  Common adverse effects such as flushing and gastrointestinal events (diarrhoea, nausea and upper abdominal pain) are mild to moderate for most of patients. Dimethyl fumarate can have an effect on the body's immune system by causing a drop in the number of the white blood cells which help to fight infection. More people in the groups treated with dimethyl fumarate experienced this than they did with placebo. We found moderate quality that people were more likely to leave the study early because of adverse events if they were treated with dimethyl fumarate than with placebo.
We identified a total of eight studies that enrolled 916 preterm infants and compared the effectiveness and safety of paracetamol versus ibuprofen, indomethacin or placebo in the treatment of a PDA in early life. When the results of the included studies were combined, the success rate for paracetamol to close a PDA was higher than that of placebo and similar to that of ibuprofen and indomethacin. Paracetamol appears to have fewer adverse effects on kidney and liver functions. In one small study that followed children to 18 to 24 months of age there was no difference in neurodevelopmental impairment. The evidence is up to date as of November 2017. Paracetamol appears to be a promising alternative to indomethacin and ibuprofen for the closure of a PDA with possibly fewer adverse effects. Additional studies testing this intervention and including longer-term follow-up are needed before paracetamol can be recommended as standard treatment for a PDA in preterm infants. Several studies are ongoing that will eventually provide additional information. Because of reports of a possible association between prenatal paracetamol and the development of autism or autism spectrum disorder in childhood and language delay in girls, long-term follow-up to at least 18 to 24 months' postnatal age must be incorporated in any studies of paracetamol in the newborn population. Although the healthcare providers were not always 'blinded' (unaware of which drug the infants received) we judged the quality of the evidence to be moderate.
We included nine studies in this review, involving 2888 male and female workers aged between 16 and 67. The studies included several types of workers: metal workers, dye and print factory workers, gut cleaners in swine slaughterhouses, cleaners and kitchen workers, hospital employees, and hairdressing apprentices. We were unable to find out whether or not the preventive measures were equally effective in all these professions because there were too few trials. The studies lasted from four weeks up to three years. Some of the preventive measures may reduce the risk of hand skin irritations. However, there were too few studies to be sure of this. The studies were too different from each other to combine in a meaningful way, and the results were too imprecise. Our results are therefore still debatable. Various barrier creams, moisturisers, and skin protection education programs were investigated. It is possible that barrier creams may slightly reduce the risk of developing OIHD. This result was based on four studies. In these studies, 29% of people who applied barrier creams developed hand skin irritations. In the control group, who did not apply barrier creams, 33% developed hand skin irritations. The results of three studies showed that moisturisers may reduce the risk of developing OIHD by a useful amount. Thirteen per cent of the people who used moisturisers developed hand skin irritations, compared to 19% of those who did not use moisturisers. Two studies showed that using a combination of barrier creams and moisturisers may reduce the risk of developing OIHD by a useful amount. Eight per cent of the people who used moisturisers and barrier creams developed hand skin irritations, compared to 13% of the control group. Based on three studies, we are uncertain whether skin protection education reduces the risk of developing OIHD. In these studies, 21% of the people who received skin protection education developed hand skin irritations, compared to 28% of the people in the control group. The safety and tolerability of these measures were not systematically addressed in these studies. However, no serious reactions to the treatments were reported. Mild reactions like itching or reddening of the skin were reported for only few people who applied the barrier creams or moisturisers. The measures to prevent hand skin irritations probably cause only few or no serious adverse effects. For barrier creams, moisturisers, or a combination of both, the quality of the evidence was low concerning the prevention of OIHD. There was not enough information and hand dermatitis was assessed differently across the studies. For educational programmes, the quality of the evidence was very low concerning the prevention of hand skin irritation. There was not enough information, hand dermatitis was assessed differently across the studies, and the studies were poorly conducted in some important respects. For the other key outcome, safety and tolerability of the treatments, the quality of the evidence was moderate because only indirect results were available.
Distinct sources of randomised clinical trials (RCTs) were searched, such as electronic databases (between 1966 and 2007). We also crosschecked references and contacted scientific societies. Eleven trials involving 398 men met the inclusion criteria. Conclusions: there is evidence that group therapy (GT) improves ED in selected patients. Focused sex GT showed greater efficacy than control group. Men who received GT plus sildenafil showed significant improvement of ED and were less likely than those receiving only sildenafil to drop out. In comparing the effectiveness of psychological interventions for the treatment of ED versus local injection and vacuum devices, no difference was found.
We identified seven trials that included 2144 participants. There were more side effects with IB, such as dryness of the nose, mucus with streaks of blood and bleeding from the nose. Limitations in this review included two studies with missing participants and four studies with unclear blinding of the participants, personnel or outcome assessors. These limitations resulted in the majority of studies having an unclear risk of bias, which raises the concern of overestimation of the overall effect of IB. We concluded from this review that IB may be effective in improving the runny nose with some side effects that are well tolerated. There is a need for more high-quality studies to determine the effectiveness of IB in relieving common cold symptoms.
In this review, the effectiveness of psychological therapies for adult patients with irritable bowel syndrome was evaluated. Studies involving cognitive behavioural therapy, interpersonal psychotherapy and relaxation therapy or stress management were reviewed. Although it is difficult to draw conclusions because of differences between studies and quality issues, the results suggest that cognitive behavioural therapy and interpersonal psychotherapy may be effective immediately after finishing treatment. It is unclear whether the effects of these therapies are sustained thereafter. These results have to be interpreted with caution as the quality of the studies was sub-optimal. Physicians should be aware of the limitations of these therapies and should choose an appropriate therapy based on the individual patient's characteristics.
This review assessed data from twenty-six studies comparing paracetamol plus codeine with placebo, and fourteen studies comparing paracetamol plus codeine with the same dose of paracetamol alone. The combination provided effective pain relief for about 40% of participants experiencing moderate to severe pain after an operation with 600 to 650 mg paracetamol plus 60 mg codeine, the dose most commonly used in these studies, and about 50% of participants with 800 to 1000 mg paracetamol plus 60 mg codeine, the dose most commonly used in clinical practice. The addition of codeine provided effective pain relief to about 10% more participants than the same dose of paracetamol alone. These single dose studies did not associate paracetamol plus codeine with any serious side effects.
Twenty relevant studies comprising a total of 986 participants (966 MS participants and 20 healthy controls) were identified and included in this review. Low-level evidence was found that neuropsychological rehabilitation reduces cognitive symptoms in MS. However, when analysed individually, 18 out of the 20 studies showed positive effects. Cognitive training was found to improve memory span and working memory. Cognitive training combined with other neuropsychological rehabilitation methods was found to improve attention, immediate verbal memory and delayed memory. It is worth noting that the small numbers of patients in the studies and some methodological weaknesses reduce the level of the evidence. To further strengthen the evidence well-designed, high-quality studies are needed.
This is an updated review. In the original review original eight studies were identified and five were high enough quality to be included. In this update no new trials were identified and so five were still included in the review. These studies were of different types of calcium channel blocking drugs and measured a variety of outcomes such as muscle strength, scales of muscle function, biochemical changes in muscle and electrocardiographic findings. Only one study showed a beneficial effect, which was an increase in muscle strength, but in this study the drug used was also associated with cardiac side effects. Adverse effects noted were mostly known side effects of calcium channel blockers.  Limitations of the review were that a meta-analysis could not be done as the trials used different calcium channel blockers and measured different outcomes, and all but one of the trials included a low number of patients. In conclusion, the review did not find calcium antagonists to have a useful effect.
When epidurals or spinals were used to replace general anaesthesia, the risk of dying during the surgery or within the following 30 days was reduced by approximately 29% (from 20 studies with 3006 participants). Also, the risk of developing pneumonia (chest infection) was reduced by 55% (from five studies with 400 participants). However, the risk of developing a myocardial infarction (heart attack) was the same for both anaesthetic techniques (from six studies with 849 participants). When epidurals (and less frequently spinals) were used to reduce the quantity of other drugs required while general anaesthesia was used, the risk of dying during the surgery or within 30 days was the same for both anaesthetic techniques (from 18 studies with 3228 participants). Also, a difference was not detected for the risk of developing myocardial infarction (from eight studies with 1580 participants). The risk of developing pneumonia was reduced by approximately 30% when a correction was made for possible missing studies (from nine studies with 2433 participants). No serious side effects (seizures, cardiac arrest, nerve damage lasting longer than one month or infection) were reported from the use of epidurals or spinals in these studies. The quality of the evidence for all six comparisons was rated as moderate because of some imperfections in how the studies were carried out. Therefore further research is likely to have an important impact on our confidence in these results and may even change the results. .
There was a trend towards an increase in live birth and pregnancy rates during and within three months of gonadotrophin treatment. The quality of the evidence was very low. We did not find enough studies to allow final conclusions about the use of gonadotrophins in the treatment of men with idiopathic male factor subfertility. The quality of the evidence was very low. More studies on this subject are needed. The evidence is current to January 2013.
We found one eligible trial, published in 2006, which analysed data from 38 people from 32 different treatment centers from the USA. The trial compared a treatment of surgery and physical therapy with physical therapy on its own. This trial did not show that the addition of surgery to a physical therapy regimen could improve the outcome for people with sickle cell disease and avascular necrosis. After a mean follow-up of three years, the combination of surgery and physical therapies did not show clinical improvement when compared with physical therapy alone. Given that the results are imprecise, we are uncertain as to whether surgery and physical therapies in combination has an important effect on hip pain, vaso-occlusive crises and acute chest syndrome. Trial authors did not report information on mortality and quality of life. The limited number of participants included in the study led to imprecise results, therefore, the confidence in the results is very low.
We searched for all randomised controlled trials that studied this form of treatment up to December 2014. We found only one trial of 173 women who were troubled by urinary leakage. On average, these women were 50 years of age. Through random assignment, two-thirds of them were treated with low-temperature heat via the urethra; the others did not receive this treatment. Researchers followed these women for 12 months. The makers of this treatment paid for the study. No information revealed whether more or fewer women complained of urinary leakage at 12 months, or whether there was a difference in the number of women having repeat surgery. The study did not show that quality of life was improved. Evidence was insufficient to show whether there was a difference in serious or minor side effects. Using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, we found no evidence for the question of whether low-temperature heat via the urethra changed the number of women who leaked. We found low-quality evidence related to serious side effects, minor side effects and quality of life when compared with no treatment because data were limited and the study was poorly conducted. We found no evidence on whether this treatment changed the number of women who underwent another surgery. Because we did not find studies that compared this treatment with other treatments, we do not know whether this treatment results in better or worse outcomes.
We reviewed the trials that compared giving MAO-B inhibitors with other types of medication in people with early Parkinson's to see if there was good evidence that MAO-B inhibitors were the best treatment to offer. However, unfortunately we only identified two trials (593 patients) so there was only limited evidence. The results showed that MAO-B inhibitors were less good at improving the symptoms of Parkinson's than either levodopa or dopamine agonists but that they may reduce motor fluctuations compared with levodopa, though not compared with dopamine agonists. MAO-B inhibitors did, however, have fewer major side effects than some dopamine agonists.
This review carefully examines all the available high-quality clinical trials on caffeine in asthma. This review was conducted to discover if people should avoid consuming caffeine before taking lung function tests. This review found that even small amounts of caffeine can improve lung function for up to four hours. Therefore caffeine can affect the result of a lung function test (e.g. spirometry) and so caffeine should be avoided before taking a lung function test if possible, and previous caffeine consumption should be recorded. It is not known if taking caffeine leads to improvements in symptoms. It may be that in order to improve the symptoms of asthma, caffeine is needed in such large amounts that the drug's adverse effects would become a problem, so more research is needed. Another clinical trial looked at the effect of caffeine on exhaled nitric oxide levels and found that there is no significant effect, so it appears unlikely that patients would need to avoid caffeine before taking this type of test. However, this is the result of just a single study so more research is needed to clarify this.
We included six studies (with a total of 784 adults and children) in this review. Five studies compared a standard dose of mannitol with control (a very low dose of mannitol or a version of mannitol which did not allow the active drug to reach the lungs) and the sixth study compared mannitol with nebulised recombinant human deoxyribonuclease (dornase alfa), both alone and taken together. Participants could continue using dornase alfa and other standard therapies, but were excluded from the five of the six studies if they were using hypertonic saline. Treatment in these studies lasted from 12 days to six months. Five studies provided the treatments to people as outpatients and in one study, the children treated were in hospital due to pulmonary exacerbations (flare ups of disease). It was difficult to combine evidence from the studies in this review due to differences in the designs of the studies, treatments examined and the settings (hospital or outpatients). Some additional information was obtained from the drug manufacturer and one study author to aid the review. The review found low- to very low-quality evidence that there is no difference between mannitol and control treatments or mannitol given either with or without additional dornase alfa in terms of quality of life. There was moderate-quality evidence of improvements in some measures of lung function across the larger studies comparing mannitol to control. Beneficial effects were also seen in the subgroup of adults and in both those who were using dornase alfa and those who were not. Cough (including coughing up blood), contraction of the airways, pain in the pharynx or larynx and post-treatment vomiting were the most commonly reported side effects on both treatments, but there was no evidence to suggest that these side effects occurred more on mannitol than on control treatments or on dornase alfa. None of the studies compared mannitol to nebulised hypertonic saline and so we can not comment on which agent is better for airway clearance. More research is needed to answer this question. We judged the quality of the evidence from this review to be of very low to moderate quality, depending on the outcome measured. We do not think that the way the studies were designed affected the results. We judged that everyone taking part had equal chances of being in either of the treatment groups and would not have known in advance or during the study which treatment they were receiving. However, the numbers of people who dropped out of the studies might affect how the results are interpreted, as well as how many people were recruited into the studies and how they were selected from all people with cystic fibrosis who could have been included. Although some of these issues were resolved when the drug's manufacturer (who also sponsored the studies) provided some additional information. It is important to realise that before people started the study, they took a test to see if they could tolerate mannitol and only those who did could carry on. This means that the results of the studies only apply to those people with cystic fibrosis who can tolerate mannitol.
When desmopressin is used, most of the children have fewer wet nights (one night less on average per week) and more become dry (19% compared with only 2% using dummy treatment in five trials involving 288 children). However, many children start wetting again when treatment stops. On the other hand, more children remain dry when alarm treatment is finished (54% after alarm compared with 35% after desmopressin in two trials involving 119 children). Adding desmopressin to alarm treatment did not result in better cure rates after the end of treatment (51% remained dry after combination treatment compared with 45% after alarm alone). Those using desmopressin (or their parents) should be warned that over-drinking before bedtime should be avoided as this may lead to serious, but rare, adverse effects. Drugs called tricyclic antidepressants have a similar effect to desmopressin and are cheaper, but have more adverse effects. There are few adverse effects with alarms, other than short-term disruption for the family. In summary, alarms take longer to reduce bed-wetting, but their effect may persist longer than desmopressin.
Three studies looking at people with chronic wounds were included in the review and found that silver-containing foam dressings did not result in faster wound healing after up to four weeks of follow-up. One study did find that the overall size of the ulcer reduced more quickly when dressed with a silver-containing foam. There is no enough evidence to recommend the use of silver-containing dressings or topical agents for treating infected or contaminated chronic wounds.
For this review, we searched for all of the surgical procedures for trigeminal neuralgia. We found 11 studies, which included 496 patients, but only three had sufficient outcome data to report. These three studies, which involved a total of 181 participants, fulfilled the inclusion criteria and form the basis of this review. The primary aim of all three studies was to determine if one technique was better than the other. All three included studies evaluated destructive techniques. None of the three studies evaluated the non-destructive procedure of microvascular decompression and this is a major drawback in the literature. One study compared two different techniques of radiofrequency thermocoagulation, in 40 participants six months after the procedure. This technique involves heating the nerve by passing an electrical current through the tip of a special needle which has been introduced through the skin into a hole in the base of the skull and into the ganglion from which the three divisions of the trigeminal nerve branch out (Gasserian ganglion). If the radiofrequency was given as pulsed treatment (which causes the tip of the needle to heat up intermittently and not continuously) the original pain in all participants returned by three months. The continuous radiofrequency treatment then had to be applied, and these participants then achieved pain control comparable to those who had received continuous radiofrequency throughout. Changes in sensation ranging from mild to severe numbness were common in the conventional (continuous) radiofrequency treatment group. A second trial, in 87 participants, looked at using one or two isocentres (specific points in the nerve) to deliver radiation to the trigeminal nerve just as it leaves the brainstem inside the skull. Use of medication afterwards was considered a surrogate measure for pain. Use of two isocentres increased the occurrence of sensory loss as a complication. Increased age and prior surgery were predictors for poorer pain relief. There were insufficient data given to judge the effectiveness of one procedure better than the other. A third study compared two techniques for performing radiofrequency thermocoagulation of the Gasserian ganglion in 54 participants. The study compared two ways of introducing the needle and guiding it, using either X-rays or a special neuronavigation system. Pain relief was measured by a questionnaire at three months. Both techniques provided pain relief (which did not differ significantly between the two arms) but it was more sustained if a neuronavigation system was used and this system also decreased side effects. All the reviewed procedures resulted in pain relief and some participants were then able to stop taking medications. However, many procedures tended to result in sensory side effects. All the studies in this review had flaws in their methods and all but two showed considerable risk of bias. There is little evidence from these trials to guide the person with trigeminal neuralgia as to the most effective surgical procedure. There is now an urgent need to evaluate the surgical interventions used in trigeminal neuralgia and to design robust studies; either randomised controlled trials or long-term prospective independently assessed cohort studies.
In the current review, data were found and analysed from 7 trials involving 404 patients randomly allocated to receive antibiotics or placebo. Although death occurred less after antibiotics (8.4%) than placebo (14.4%), as did infected pancreatic necrosis (19.7% versus 24.4%) and other infections (23.7% versus 36%), the differences were not statistically significant and so genuine benefit cannot be confirmed. There were no major problems with antibiotic resistance, and fungal infections were similar (3.9% versus 5%). The quality of studies was variable and only two were ‘blinded’, whereby investigators and patients were unaware of which treatment patients received. Many different regimens were used, and of the two main types of antibiotics used, a beta-lactam appeared to work better. Only one type of antibiotic (imipenem) was considered on its own, showing a significant decrease in infection of the pancreatic necrosis. Although we cannot confirm benefit from the use of prophylactic antibiotics in this condition, consistent trends towards a beneficial effect nevertheless remain. Further, better designed studies, ideally with beta-lactam antibiotics, are required.
Six included trials assessed the effects of oral thiol derivatives.Three of these trials compared oral N-acetylcysteine to placebo; one compared oral N-acetylcysteine, oral ambroxol and placebo; and one compared oral carbocysteine and oral ambroxol (no placebo). None of the trials showed an overall significant benefit in any of the outcome measures of this review. Oral thiol derivatives were generally well-tolerated with no major adverse effects. In summary, the trials included in the review did not provide any evidence that nebulized or oral thiol derivatives were either beneficial or harmful to people with cystic fibrosis. Further research investigating the effects of thiol derivatives in people with cystic fibrosis is required before their use can be recommended.
This review assessed whether testing for undiagnosed cancer in people with a first unprovoked VTE (DVT or PE) was effective in reducing cancer and VTE-related illness and death. We found four studies with 1644 participants (current to July 2018). Two studies compared extensive cancer tests with tests carried out at the physician's discretion and two studies compared cancer tests plus scanning with cancer tests alone. Combining the results of the two studies showed that extensive testing had no effect on the number of cancer-related deaths. Additionally, extensive testing did not identify more people with cancer. However, extensive testing did identify cancers at an earlier stage (approximately 10 months earlier) and cancers were less advanced in people in the extensive testing group than in people in the group with tests carried out at the physician's discretion. Neither study looked at the number of deaths due to any cause, deaths and illness associated with VTE, side effects of cancer tests, side effects of VTE treatment or participant satisfaction. Two studies that compared tests plus scanning with tests alone showed that adding computed tomography scanning had little or no effect on the number of deaths, cancer-related deaths, illness associated with VTE; nor did it identify more people with cancer, or show a clear difference in time to diagnosis or stages of cancer diagnosed. Neither study looked at deaths associated with VTE, side effects of cancer tests, side effects of VTE treatment, participant satisfaction or quality of life. When comparing extensive tests versus tests at the physician's discretion, the quality of the evidence was low due to bias caused by two of the studies stopping early. When comparing tests plus PET/CT scanning with tests alone, the quality of the evidence ranged from low to moderate due to imprecision caused by a low number of events and bias due to lack of blinding of people assessing the effects. This review found that there are too few trials to determine whether testing for undiagnosed cancer in people with a first unprovoked VTE (DVT or PE) is effective in reducing cancer and VTE-related deaths and illness. Further good-quality and large-scale studies are required.
The review found some weak evidence from only two studies with 56 patients that flapless placement of dental implants reduces postoperative discomfort (pain and swelling), without jeopardising implant success in selected patients. There is insufficient evidence to recommend any specific flap or suturing technique. There is only a small study (10 patients) suggesting that soft tissue grafts from the palate improve gum thickness and aesthetics. There are no studies evaluating whether there is a benefit in increasing the amount of firm gum surrounding dental implants but there is a small trial suggesting that it is possible to increase the amount of firm gum surrounding dental implants using either tissue taken from the palate or a porcine-derived collagen matrix at the price of considerable postoperative pain/discomfort and aesthetic deterioration (there were several cases where the gum receded exposing the metal of the implant).
We reviewed the evidence up to November 2016. We found four studies, including 1342 people, that attempted to answer this question. All participants had asthma; participants in three studies were children and those in one study were adults. Three studies took place in the United States and one in the Netherlands; studies lasted from six months to two years. Different studies used different methods of shared decision-making, including face-to-face discussions, telephone calls, and online messages. Because these studies were conducted in different ways, we were unable to combine their findings. We found evidence from individual studies indicating that shared decision-making may improve quality of life and asthma control and may reduce healthcare visits for asthma. Shared decision-making may also help people to take their asthma inhaler(s) more regularly owing to better understanding of why they need to do that. Going through this process may make people feel more satisfied with their care, as they may feel empowered about making choices. However, all of these findings were reported by different studies, and some studies showed benefit of shared decision-making, while others did not. It is important to mention that none of these studies looked into whether shared decision-making causes unwanted side effects. All four studies measured how well the shared decision-making intervention had been delivered or received but did this in different ways. We were not very confident in the quality of the evidence presented in this review. We were concerned about the small number of studies and about differences in the way included studies were designed. Also, participants knew which group they were in (i.e. shared decision-making or standard care), and this may have affected how they answered questions about their asthma during the trial. Some evidence suggests that shared decision-making might help people with asthma, but we are not sure whether it is helpful. In the future, larger studies that include adolescents while looking out for side effects, harms, and benefits should prove useful in answering this question.
During searches updated to January 2017, we found one study (with low risk of bias) that compared oral dextrose gel versus placebo for prevention of low blood glucose levels in 415 at-risk babies. Evidence from this single study suggests that in babies at risk, oral dextrose gel followed by a feed is associated with reduced risk of low blood glucose levels when compared with placebo (high-quality evidence). Results showed no statistically significant differences between oral dextrose gel and placebo in terms of the number of adverse events (moderate-quality evidence), risk of separation of baby from mother for treatment of low glucose levels (moderate-quality evidence), exclusive breastfeeding at discharge (moderate-quality evidence), or continued breastfeeding at six weeks of age (moderate-quality evidence). We must be careful when interpreting the evidence for adverse events and separation of mother and baby, as a small number of events have been reported for these outcomes. Researchers provided no data on long-term outcomes including developmental and disability outcomes. Available evidence came from only one study, and no long-term outcome data have been reported. Additionally, this study considers only oral dextrose gel compared with placebo and does not consider other measures that could potentially prevent hypoglycaemia. Therefore, not enough evidence is available at this time to support the routine use of oral dextrose gel for prevention of hypoglycaemia in newborn babies at risk. Childhood follow-up of the single study included here is under way, and an additional ongoing study is seeking to determine the effect of oral dextrose gel on preventing admission to the neonatal intensive care unit (NICU). We advise waiting for data on outcomes of these additional studies to assess the longer-term safety and efficacy of oral dextrose gel for prevention of neonatal hypoglycaemia.
We wanted to know the benefits and harms from bortezomib treatment for myeloma. We searched medical databases and trial registries until January 2016. We included studies of bortezomib compared to no bortezomib, with either the same or different background therapy or compared to other drugs. Studies of newly diagnosed and relapsed myeloma were included as well as those that compared different doses, ways of administering bortezomib and treatment schedules. We found 16 studies involving 5626 myeloma patients. The results of this review suggest that bortezomib can lead to better survival, a longer time without progression and better response rates compared to those not receiving bortezomib. Treatment with bortezomib causes a number of side effects including: low levels of some blood cells; gastro-intestinal effects such as constipation, diarrhoea, nausea and vomiting; nerve pain and tingling in hands and feet, as well as infection. A greater risk of heart problems was seen in one of the comparison groups studied. Risk of death from bortezomib treatment was uncertain in either group analysed. Only four studies assessed quality of life and could not be analysed together. We judged quality of the evidence as high to moderate for mortality or number of deaths, whereas it was considered low-quality evidence for progression-free survival. the quality of evidence for adverse events was highly variable (low to high). For assessment of treatment-related death, there was no evidence of a difference, with low-quality evidence in one comparison (bortezomib compared to no bortezomib with the same background therapy) and very low-quality evidence in comparison two (bortezomib compared to no bortezomib with different background therapy or compared to other drugs). Patients receiving bortezomib had better response rates, longer time without progression and appeared to live longer compared to those not receiving bortezomib, however patients receiving bortezomib experienced more side effects. Other proteasome inhibitor drugs have also been developed, therefore further research should focus on whether these newer drugs provide additional benefits and fewer side effects than bortezomib. More studies on health-related quality of life are also needed.
Eight trials were found, which included around 1100 people, although information was only available for 1036 women. There was not enough evidence to determine whether the urodynamic tests led to better outcomes. There was some evidence that urodynamic testing increased the number of people given drugs but not the number of people undergoing surgery. This did not result in any difference in the number of people who leaked urine, and it was not known whether they had a better quality of life. More research is needed in which people are randomised to having treatment decisions based on either their symptoms and examination alone or after taking into account the extra information provided by urodynamic tests.
Overall the mental health and general functioning of people taking chlorpromazine or haloperidol improved. Compared to nowadays fewer people in both arms of the trial left the study early but those taking chlorpromazine were statistically more likely to do so. This was also the case when the oral medications were analysed on their own, but not in the case of the injected form. There was a suggestion that people may leave the study because of either adverse events or because the treatment did not work well. Haloperidol had statistically more movement side effects while chlorpromazine was statistically more likely to cause low blood pressure (hypotension). Although these trials show both haloperidol and chlorpromazine to be effective drugs for schizophrenia, a lot of data were not able to be used because some measures were not reported. Therefore the area would benefit from a new trial with a large number of people and lasting at least a year. (Plain language summary prepared for this review by Janey Antoniou of RETHINK, UK www.rethink.org).
We looked for trials comparing oral non-steroidal anti-inflammatory drugs to a a placebo (a tablet that contained no active medicine). We looked for any dose level. but the trial had to run for at least two months in people with cystic fibrosis. We found 17 trials and included four of these with a total of 287 people aged five to 39 years; one further trial has not yet been published in full and two are still ongoing; we will assess these when we have more information. Three of the four included trials compared ibuprofen to a placebo; two of these trials were run in the same center and used some of the same people. One trial compared a drug called piroxicam to placebo. The longest trial lasted four years. We aimed to report on lung function, nutritional status, lung x-rays, how often intravenous antibiotics were needed, details about hospital admissions, survival and side effects. We combined results from the two largest ibuprofen trials and showed that those taking ibuprofen had a lower annual rate of decline in lung function which was consistent across three lung function measurements. We then looked at these results split by age (even though we did not originally plan to do this) and found that two of the measurements showed a slower rate of annual decline in lung function in younger children. Results from four trials showed that fewer participants in the ibuprofen group were admitted to hospital at least once compared to placebo, although it was not clear if the difference was just chance or not. In one trial, people taking a long-term high dose of ibuprofen were less likely to need intravenous antibiotics, had better nutritional status and healthier lungs as seen by X-ray. No major side effects were reported in the trials, but they had not been designed to show differences in the rates of side effects. To summarize, we found evidence showing that a high dose of a non-steroidal anti-inflammatory drug, most notably ibuprofen, may slow the progression of lung damage in people with cystic fibrosis, especially in younger people. The long-term safety results are limited but we feel that there is enough evidence to suggest that non-steroidal anti-inflammatory drugs be temporarily stopped when people with cystic fibrosis are receiving intravenous aminoglycosides or other drugs that may badly damage the kidneys. The trial of the drug piroxicam did not report many results in a form that we could analyse in the review. We did not have any results for our main outcome of lung function. The only results we had reported no difference between the piroxicam group and the placebo group for the number of hospital admissions. We judged the evidence to be of moderate quality overall. We thought the three ibuprofen trials had a good or adequate level of methodological quality with little risk of bias to the results, but used a range of different outcomes and summary measures. We did not have any concerns with regards to risks of bias for the trial comparing piroxicam to placebo.
We searched six databases for relevant research. This is an update of a previously published review, and the date of the most recent search was February 2017. We found 78 studies on the effects of interventions aimed at family and carers with the goal of reducing children’s exposure to tobacco smoke. These studies included parents and other family members, child care workers, and teachers involved in the care and education of infants and young children (from birth to 12 years of age), and used a variety of interventions, including different kinds of counselling, brief advice, and educational materials. Only 26 studies reported that an intervention was successful in reducing children’s exposure to tobacco smoke. These studies used a range of interventions. Nine studies used more intensive counselling methods or motivational interviewing, but in other studies, these types of interventions were not effective. Of the 52 studies that did not show a significant reduction in child tobacco smoke exposure, 19 used intensive counselling methods or motivational interviewing. One study successfully reduced children's asthma symptoms by using motivational interviewing. This review does not show whether any particular interventions reduced parental smoking and child smoke exposure more effectively than others. The quality of evidence ranged from low to very low. Future studies should aim to provide evidence of higher quality by addressing study design problems, including more participants, and describing interventions in more detail.
This findings of this review of 21 trials (7243 participants) do not allow certainty about the relative efficacy of ciclesonide compared to older inhaled corticosteroids, especially at higher doses. The results of the review to date do not indicate whether ciclesonide provides a significantly more useful safety profile that other inhaled corticosteroids at similar equivalent doses. However, the finding of lower oral candidiasis in patients treated with ciclesonide compared to fluticasone may be important for those patients who experience oral thrush with their current ICS. In addition, further studies in children are required to obtain data on the side-effect profile of ciclesonide in this population.
Most trials have compared the two most commonly used corticosteroids before early birth, dexamethasone and betamethasone. In this review of 12 trials (involving 1557 women and 1661 infants) of moderate quality, 10 trials compared dexamethasone and betamethasone; one trial compared two different ways of giving dexamethasone and one trial compared two different ways of giving betamethasone. We found that dexamethasone and betamethasone showed similar results, although there was less bleeding of the brain and a shorter length of neonatal intensive care unit hospital stay for dexamethasone compared with betamethasone. On the basis of one trial, giving dexamethasone by injection (intramuscularly) may be better than giving the drug to the mother by mouth (orally). Usually the drug is given in two doses 24 hours apart and one trial showed that this interval could perhaps be reduced to 12 hours if required. We need more studies to establish which is the best drug and what is the best way to give it, and babies in these trials need to be followed up over a long period to monitor any effects on child and adult development.
This review found that giving dexamethasone (a corticosteroid drug) around the time of extubation can help prevent swelling in the baby's throat that might require reinsertion of the tube. However, the review found that there are adverse effects of dexamethasone. The benefits only outweigh the risks for babies at high risk of complication (such as those who have received several, or prolonged, intubations).
In summary, there is no evidence to support the first-line use of minocycline in the treatment of acne. All of the trials showed that, on average, people treated with minocycline experienced an improvement in their acne. However, no study conclusively showed any important clinical difference between minocycline or other commonly-used therapies. The analysis found that minocycline may act more quickly than oxytetracycline or tetracycline, but there is no overall difference in the end. There is no evidence that it is more effective in acne that is resistant to other therapies, or that the effects last longer. Although it is often claimed that the more expensive once-daily slow-release preparation is a more attractive option to teenagers with acne, the evidence in this review does not show it to be any better or safer compared to other oral antibiotics that have to be taken more frequently. Despite a thorough search for evidence, it is still not known which of the tetracyclines are the safest to take overall as they are all associated with side-effects. The only conclusion that we could make was that people treated with minocycline for acne are at a significantly greater risk of developing an autoimmune (lupus-like) syndrome than those given tetracycline or no treatment.
This Cochrane Review is an individual patient data based meta-analysis and the aim was to assess whether this type of radiotherapy could improve survival. We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck cancers and grouped trials into three pre-specified categories: hyperfractionated, accelerated without total dose reduction and accelerated with total dose reduction. The results of this meta-analysis suggest that altered fractionation radiotherapy improves survival in patients with head and neck cancer. Comparison of the different types of altered fractionation radiotherapy suggests that hyperfractionation provides the greatest benefit. Individual patient data meta-analysis is a long process and this review included all eligible trials which had completed recruiting patients by 1998. A major update of the analysis, including data from more recent trials, is currently underway.
This systematic review of randomized controlled trials assessed the effects of behavioral interventions on promoting condom use among women living with HIV, a population at higher risk to other sexually transmitted infections (STIs). Based on five eligible studies, we found that behavioral interventions promoting consistent condom use in HIV-positive women did not have a significant impact on outcomes, when compared to standard care or minimal HIV-related support. However, these findings should be used with caution since they are based on a few small trials that were targeted specifically towards HIV-positive women. New research is needed to assess the potential personal and public health gains that could arise from a combination of interventions that promote safe sexual behavior and adopt a harm reduction approach, particularly in developing countries, where HIV infection rates among women remain high.
The authors of this review evaluated the efficacy and safety of preoperative physical therapy with an exercise component in cardiac surgery patients. From the pertinent literature, eight studies met the inclusion criteria, comprising a total of 856 participants. The results showed that preoperative physical therapy reduced the number of patients who experienced atelectasis or pneumonia but not the number of patients who experienced pneumothorax, prolonged ventilation or postoperative death. Patients who had preoperative physical therapy had an earlier (on average by more than three days) discharge from the hospital. Information on adverse events was limited but those studies that did report on adverse events reported none. None of the studies reported on the costs of preoperative physical therapy. The authors concluded that preoperative physical therapy, especially inspiratory muscle training, prevents some postoperative complications including atelectasis, pneumonia, and length of hospital stay.
This review examines the effectiveness of individual psychosocial interventions in the first 12 months after diagnosis. The psychosocial interventions involve a 'trained helper' providing therapeutic dialogue, sometimes referred to as talking therapy, with an individual diagnosed with cancer with the aim of improving quality of life and emotional wellbeing. The review combines research data from 1249 people who took part in clinical trials to test psychosocial interventions. The results are inconclusive. No improvement in general quality of life was found, but small improvements in 'illness related' quality of life were observed. No improvements in anxiety or depression were found, but small improvements in mood were detected. Nurse-led interventions using telephone and face-to-face delivery appear to show some promise. Future research should test assessment methods designed to identify patients who may benefit from psychosocial interventions, such as patients who are at risk of emotional problems; evaluate which type of 'trained helper' is the most appropriate professional to deliver psychosocial interventions for cancer patients; and conduct economic appraisals of the cost-effectiveness of interventions.
We searched for all relevant studies until 4 September 2015. We found seven studies, six of which we identified previously and one retrieved for this update. All of the studies assessed the impact of the intervention on the mental health of persons with an intellectual disability; none considered the physical health. Those studies used different interventions, including giving persons with an intellectual disability more health services, psychological support, and treating them at home, instead of at the hospital. Studies mainly looked at how the interventions helped the behavioural problems of those with an intellectual disability, how much burden they caused the care givers, and how much they cost. No study assessed adverse events. Community-based behaviour therapy might decrease behavioural problems. We are uncertain whether other interventions make any difference in reducing behavioural problems. There was limited evidence about how those interventions helped care givers to deal with the burden of caring for their relatives with an intellectual disability, or how much they might cost compared with the usual care already provided. uthors' conclusions There is little information on different ways to organise services for people with intellectual disabilities. Most studies focused on people who had intellectual disabilities and mental health problems. There were no studies on people who had intellectual disabilities and physical problems.
Our search identified just one randomised controlled trial which evaluated 91 participants who had tinnitus for at least six months and some degree of hearing loss. It compared those receiving hearing aids to those receiving sound generators. The average age of the patients was 38 and there were 40 women and 51 men. The study took place in two centres in Italy and the USA. The result from the single study we reviewed was not definitive and was compatible with only small differences between the effect of hearing aids and sound generators. We also found another relevant study which has not yet been completed. We believe further high-quality trials are needed. The quality of this evidence is moderate to low. This review is up to date to August 2013.
IFN and GA demonstrated only partial efficacy that could be ascribed to the fact that in the studies that lead to their approval they have been initiated in patients with a disease history of several years. The objective of this review was to assess IFN beta and GA efficacy in preventing the conversion to clinically defined multiple sclerosis in patients after the first demyelinating events. Among the pertinent literature, only three studies were found to test the efficacy of IFN beta including a total of 1160 participants (639 under treatment, 521 under placebo); while no published study testing the efficacy of GA was found. The review found that early interferon beta-1a treatment is effective in preventing the conversion of the first isolated demyelinating episodes into clinically definite MS both after one year and two years of follow-up. Side effects and adverse events occurrence was the same as reported by the many studies on IFN beta treatments in MS patients with different levels of the disease. More research is however needed to evaluate the long term preventing efficacy of these drugs and dosages.
Hence, the aim of this review was to assess and synthesise the available literature on the management of cough in cancer patients in order to improve practice recommendations. Studies with chemotherapy or radiotherapy were excluded. An extensive literature search yielded 17 studies for evaluation. For this update, we did not identify any additional studies for inclusion. Eight of the studies were about the use of brachytherapy (a technique where a radiation source is placed inside the bronchus in the lung for lung cancer or next to the area requiring treatment), use of laser resection or photodynamic therapy (a treatment that uses a drug plus a special type of light to kill cancer cells). Nine studies assessed the effects of a number of different medications, including codeine and morphine. Overall, the research was of poor quality with significant methodological problems, hence no credible evidence was available in the literature to guide practice. Acknowledging these limitations, brachytherapy in a variety of radiation doses was found to be helpful in selected patients. Some pharmacological treatments were found to be helpful, in particular morphine, codeine, dihydrocodeine, levodropropizine, sodium cromoglycate and butamirate citrate linctus (a cough syrup), although all studies had significant risk of bias and some reported side effects. No practice recommendations could be drawn from this review. There is an urgent need to increase the number and quality of studies evaluating the effects of interventions for the management of cough in cancer.
We included four studies. One study looked at the effect of subsidising ACT drugs for children under five years of age and three studies looked at subsidising ACT drugs for people of all ages. All studies were from rural districts in East Africa (Kenya, Uganda and Tanzania). ACT price subsidies were accompanied with activities (such as staff training at shops and pharmacies, community awareness and mass media campaigns) to promote appropriate use of antimalarial drugs in all except one study. In all four studies, the effect of subsidising the drugs was compared to not subsidising the drugs. Price subsidies ranged from 80% to 95% of the actual price; vouchers to households were used in one study. The findings from these studies indicate that ACT subsidy programmes: (i) lead to a substantial increase in the number of children under five years of age who used ACTs when they had a fever (high certainty evidence); (ii) lead to a substantial increase in the number of shops that stocked ACTs for children under five years of age (high certainty evidence); we could not draw any conclusion on the effect on the number of shops that stocked ACTs for patients of any age because the quality of evidence was very low; (iii) lead to a substantial decrease in the price of ACTs for children under five years of age (high certainty evidence); (iv) lead to a substantial increase in the market share of ACTs for children under five years of age (high certainty evidence); and (v) lead to a decrease in the use of older, less effective antimalarials among children under five years of age (high certainty evidence). None of the studies measured whether the subsidy programmes led to any harmful effects (such as the inappropriate use of ACTs, in other words people who receive ACTs but do not actually have malaria). The review findings also showed that subsidising ACT prices using vouchers lead to an increase in the likelihood that an illness was treated with an ACT among people seeking treatment for fever or suspected malaria. However, vouchers also lead to an increase in inappropriate use of ACTs (high certainty evidence).
The last search for trials was in May 2018. We assessed the evidence from 13 clinical trials in which people received either carbamazepine or phenobarbitone and their treatment was decided randomly. We were able to combine data for 836 people from six of the 13 trials; for the remaining 619 people from seven trials, data were not available to use in this review. Key results Results of the review suggest that people are likely to stop taking phenobarbitone treatment earlier than carbamazepine treatment, because of seizure recurrence, side-effects of the drug, or both. Results also suggest that recurrence of seizures after starting treatment with phenobarbitone may happen later than treatment with carbamazepine (and therefore a seizure free period of 6 months or 12 months may occur earlier with phenobarbitone than with carbamazepine) for people with focal onset seizures, and vice-versa for people with generalised onset seizures. Some side effects reported by people taking carbamazepine and people taking phenobarbitone were abdominal pain, nausea, vomiting, tiredness, motor problems (such as poor co-ordination), cognitive problems (poor memory), rashes and other skin problems. Behavioural side effects such as aggression were reported on both drugs in three trials in children. Quality of the evidence Some of the trials contributing data to the review had methodological problems, which may have introduced bias and inconsistent results into this review, and some individuals over the age of 30 with newly diagnosed generalised onset seizures may have had their seizure type wrongly diagnosed. These problems may have affected the results of this review and we judged the quality of the evidence provided by this review to be moderate to low quality. We do not suggest using the results of this review alone for making a choice between carbamazepine or phenobarbitone for the treatment of epilepsy. We recommend that all future trials comparing these drugs or any other antiepileptic drugs should be designed using high-quality methods to ensure results are also of high quality.
We included 25 clinical studies in which people are randomly put into one of two or more treatment groups (called 'randomized controlled trials'), with results reported from a total of 1688 participants (929 females, 759 males). Participants were 29 to 72 years old. Eight trials compared participants receiving adductor canal block against patients receiving saline. A total of 15 RCTs compared adductor canal block versus femoral nerve block. The evidence is current to October 2018. No trial was funded by industry. We are uncertain whether patients treated with adductor canal block have lower pain intensity at rest or during movement (e.g. walking) compared with those who received only saline. It is unclear whether rates of adverse events after taking opioids (e.g. nausea) or after accidental falls during postoperative care are lower. It is also uncertain whether patients receiving adductor canal block show different postoperative pain intensity at rest and during movement compared to those treated with femoral nerve block. We noted no differences in adverse events after taking opioids and after accidental falls. We rated the quality of evidence for many outcomes as low or very low. In contrast, we rated pain at rest (at 24 hours) as high-quality evidence.
This review included five studies that examined the effects of prolotherapy injections on 366 patients with low-back pain that had lasted for longer than three months. Because these studies used different types of prolotherapy injections and different treatment protocols, their results could not be combined. The five studies we examined were therefore divided according to whether they used prolotherapy injections alone or combined prolotherapy injections with spinal manipulation, exercise, and other treatments. Of the five studies we reviewed, three found that prolotherapy injections alone were not an effective treatment for chronic low-back pain and two found that a combination of prolotherapy injections, spinal manipulation, exercises, and other treatments can help chronic low-back pain and disability. Minor side effects such as increased back pain and stiffness were common but short-lived. Based on these five studies, the role of prolotherapy injections for chronic low-back pain is still not clear.
The purpose of the review was to see whether biofeedback, taught in prenatal classes, would have an effect in relieving pain during labour. The review includes four studies (involving 186 women who were pregnant for the first time). The randomised controlled studies were very different, and of poor quality, making it difficult to draw any firm conclusions. Most studies assessed the effects of electromyographic biofeedback, which measures muscle tone. There was no significant evidence of a difference between biofeedback and control groups in terms of assisted vaginal birth, caesarean section, augmentation of labour and the use of pharmacological pain relief. There was not enough information on electromyographic to assess its effect on pain during labour. This review is one in a series of Cochrane reviews examining pain relief in labour, which will contribute to an overview of systematic reviews of pain relief for women in labour (in preparation).
We included studies that compared adjustment of asthma medicines by counting sputum eosinophils versus usual care. To be included, the studies has to decide who would be in which group by chance. The participants all had asthma, diagnosed according to asthma guidelines. The most recent search for studies was undertaken in February 2017. This updated review includes six studies involving 382 people with asthma (55 children/adolescents, 327 adults). The studies varied in several ways including study duration and follow-up, sputum eosinophil counts used for adjusting medication and the way the asthma attacks were defined. Studies were between 6 and 24 months long. The age spread of participants in the studies was 12 to 48 years. We found that guiding asthma medicines based on sputum eosinophil counts (compared to a control group) reduced the number and severity of asthma attacks in adults. In the control group where treatment was guided according to clinical symptoms, 82 participants out of 100 had at least one attack. This was reduced to 62 out of 100 in participants who had their medications guided by sputum eosinophil count. We are not certain about the effect on other measures, such as quality of life or dose of inhaled steroids needed. There is not enough data in children to assess whether using sputum eosinophil is useful. We are moderately confident in the evidence for any asthma attack and hospital admissions. We were concerned about the different ways the studies defined asthma attacks and the small number of hospital admissions overall, which makes it harder to detect a difference. We are less confident in the evidence about the dose of inhaled steroids. This is because the studies used very different doses. Also, we cannot tell if the eosinophil-guided treatment reduced or increased the steroid dose overall.
We included eight studies (specifically, randomised controlled trials (RCTs)) with a total of 559 people aged between 17 and 76 years old. The evidence is current to April 2018. All studies recruited outpatients from endoscopy centres (centres that specialise in an examination done with a flexible tube with a camera that is inserted into stomach) in several countries. The antibiotic combinations tested were very different in the included studies, as were the doses of NAC (600 mg to 1800 mg per day). NAC was compared with placebo (dummy pill) or nothing. We are uncertain whether the addition of NAC to antibiotics improves H pylori cure rates compared with the addition of placebo or no NAC. Any possible beneficial effect of NAC should be regarded cautiously because the included studies were very different and of low certainty, with some flaws that could have compromised their results and consequently, the results of this review. We are uncertain whether NAC is associated with a higher risk of gastrointestinal or allergic adverse events compared with placebo or no NAC. There were no reports of toxic adverse events amongst the included studies. Further large, well-designed randomised clinical studies, with good reporting standards and appropriate collection of effectiveness and safety outcomes should be done, especially for current recommended antibiotic combinations. The overall certainty of the evidence for eradication rates ranged from very low to low. Five studies provided information on adverse events (side effects), and the certainy of evidence was very low. The included studies were poorly conducted and this reduced our confidence in the results.
We included four studies comparing a freeze-all strategy with a conventional IVF/ICSI strategy in a total of 1892 women undergoing assisted reproductive technology. The evidence is current to November 2016. We found evidence showing seemingly no difference between the strategies in cumulative live birth rate per woman. Our findings suggest that if the cumulative live birth rate is 58% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 56% and 65%. Time to pregnancy was not reported as an outcome in in the included studies, but it can be assumed to be shorter using a conventional IVF/ICSI strategy including fresh transfer in the case of similar cumulative live birth rates, as embryo transfer is delayed in a freeze-all strategy. Not performing a fresh transfer (freeze-all strategy) lowers the OHSS risk for women at risk of OHSS. Our findings suggest that if the OHSS rate is 7% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 1% and 3%. The evidence was of moderate to low quality due to serious risk of bias and (for some outcomes) serious imprecision. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study, unit of analysis error, and absence of adequate study termination rules.
The evidence is current to February 2015. In this review one randomised controlled trial was identified that compared giving platelet transfusions at a low platelet count (25 x 109/l) versus giving platelet transfusions at a higher platelet count (50 x 109/l) prior to insertion of a central line to prevent bleeding. This trial is still recruiting and is due to complete recruitment in December 2017. There were no trials that compared no platelet transfusions versus giving platelet transfusions at a prespecified platelet count. There are no results from the one eligible study because it is still recruiting participants. This ongoing study (expected to recruit 165 participants) will be unable to provide sufficient data for this review's primary outcomes because major bleeding and mortality are uncommon. We would need to design a study with at least 4634 participants to be able to detect an increase in the number of people who had major bleeding from 1 in 100 to 2 in 100. There is no evidence from randomised controlled trials to answer our review questions.
These findings, however, are limited by the relatively short-term of clinical controlled observations which in all studies but one lasted for no more than three months. Subjective evaluations of these patients as given by their doctors were consistently positive and no noticeable side effects were evidenced in the various studies over the years.
The review includes 67 randomized controlled trials (5438 people). The trials included patients of all ages and both genders undergoing all types of surgery. The evidence was from studies available to October 2015. Forty-five trials compared a warming system to a control intervention, 18 compared different types of warming systems, and 10 compared different modalities of the same warming system. Forced-air warming was the most studied system. Active warming had some beneficial clinical effects on the patient. It reduced the risk of a major complication of heart and circulation in one trial in people with substantial disease of that system, but the evidence remains inconclusive. Active warming reduced the rate of infection and complications of surgical wounds.. This effect was shown in two quite large trials in people undergoing abdominal surgery; forced-air warming was applied exclusively before the operation in one study, while in the other it was applied during the operation. Patients receiving active warming systems had about one-third the risk of postsurgical chills or shivering compared to those receiving control treatment (29 trials, 1922 people). Thermal comfort was increased for the patient compared with the control intervention (10 trials involving 700 people). On the other hand, warming made little or no difference to the risk of death, blood loss or the need for a blood transfusion. We found no differences in the number of non-fatal heart attacks, in anxiety or in pain, compared with people in the control groups. The trials in the review did not allow us to identify which warming system was better. However, there was an indication from one trial at low risk of bias that results were better when systemic warming was extended to the period before the operation in people undergoing major abdominal surgery. We could only get limited information from the study reports regarding adverse effects. In some cases the trials reported that there had been no adverse effects. The quality of the evidence was low for surgical site infections and complications of the heart and circulation. This is because very few trials with few events reported on these outcomes, although they were at low risk of bias. Patients differed in the types of surgery, with different complexities and duration, the type of anaesthesia, patient age, the severity of the condition and other illnesses. The trials did not last long, which made it difficult to detect clinical effects. These outcomes are also strongly influenced by other management components during the operation that we did not evaluate in this review. While some studies applied a single intervention, others used two or more interventions in combination, and/or included other methods of passive warming. The control group did not always consist of a 'pure control' without active heating, and sometimes patients also received another intervention as part of usual care. All these reasons may explain the diversity that we observed for some outcomes among the studies. The temperature of the control group may also have been more strictly controlled, as there is now widespread awareness of the risk of hypothermia.
Due to the limited number of patients and trials, and significant differences between the included trials, the conclusion may be weak. There was insufficient high quality evidence to determine whether or not knee length and thigh length graduated compression stockings differed in their effectiveness in terms of reducing the incidence of DVT in hospitalised patients. The majority of patients analysed in this review also received heparin and physiotherapy, along with the use of either knee length or thigh length stockings. A major multicentre RCT is required. In the meantime, the decision on which type of stocking to use in clinical practice is likely to be influenced by factors such as patient compliance, ease of use and cost implications.
We identified a total of three trials including 295 participants, of whom 148 were randomly chosen to receive primary closure and the remaining patients had T-tube drainage after laparoscopic exploration of common bile duct. All three trials were at high risk of bias (risk of underestimating or overestimating the benefits and harms of the intervention). There were no deaths in either group. There was no significant difference in the serious complication rate (approximately 97 complications per 1000 patients in the T-tube group versus 61 complications per 1000 participants in the primary closure group) or in the proportion of participants who developed serious complications (11.3% in the T-tube group versus 6.2% in the primary closure group). Although the complication rates in the T-tube group appear to be twice as high as those in the primary closure group, there is a possibility that this was not a true observation but rather a difference that occurred by chance (similar to there being one chance in eight of flipping a coin and having it come up heads or tails four times in a row). For this reason, we cannot be sufficiently confident scientifically that these differences were not just due to chance and that is the reason why we have stated that there was no 'significant' difference. Of course, if such a difference truly exists, it would be clinically important. None of the trials reported the quality of life of the participants. The average operating time was significantly longer in the T-tube group than in the primary closure group (by about 20 minutes). The average hospital stay was significantly longer in the T-tube group than in the primary closure group (by about three days). Participants returned to work significantly later in the T-tube group than primary closure group (by about eight days). Use of T-tube appears to increase the cost without providing any benefit to the patients. Further randomised trials with low risk of bias (low chance of arriving at wrong conclusions because of prejudice by healthcare providers, researchers, or patients) with longer follow-up period are necessary. Until the results from such trials are available, we discourage the routine use of T-tube after laparoscopic common bile duct exploration.
In this review, our primary outcomes were to assess if the addition of low-dose vitamin K to warfarin had an effect on the time taken to the first INR in range; the mean within the therapeutic range; or any adverse events, such as thromboembolic events, haemorrhage, or mortality. We found two studies that met our inclusion criteria. Neither study reported the time taken to the first INR in range. One study was only available in an abbreviated format, so we were unable to interpret the results fully. Nonetheless, it was suggested that the addition of vitamin K had no benefit. A second six-month study gave a small dose of vitamin K (150 mcg daily) or placebo to participants taking warfarin with existing poor INR control. This study reported the mean time in therapeutic range as a percentage and found that in the group of participants deemed to have poor INR control, the addition of 150 mcg oral vitamin K significantly improved their anticoagulation control. However, the study was relatively small. Neither study reported any adverse events, such as thromboembolism, haemorrhage, or death. We conclude that further larger, higher quality studies are needed to conclude whether adding vitamin K to warfarin for patients starting or already on warfarin improves their anticoagulation control.
This review is up-to-date as of 24 May 2019. We included 26 studies with a total of 2435 children aged between 2 and 16 years. The studies were carried out between 2002 and 2019 in dental clinics in the UK, USA, the Netherlands, Iran, India, France, Egypt, Saudi Arabia, Syria, Mexico, and Korea. We included studies comparing the use of different equipment like audiovisual glasses or a computerised device for injection called the wand, or dentist interventions like hypnosis, counter-stimulation/distraction, video modelling, to increase the acceptance of delivery of local anaesthetic. These interventions were compared against delivery of local anaesthetic using a conventional syringe (usual care), or any other dental equipment or dentist intervention. Interventions were given just before the injection and others were given just before, during the injection, and continued during the dental treatment. The evidence was uncertain for audiovisual distraction (using 3D video glasses as distraction) compared to conventional treatment. The evidence was uncertain when comparing the wand to conventional treatment. The evidence was also uncertain for counter-stimulation/distraction compared to conventional treatment and for hypnosis compared to conventional treatment. Other comparisons considered included pre-cooling of the injection site, the wand versus another electronic system called Sleeper One, the use of a camouflage syringe, use of an electrical counter-stimulation device, and video modelling. They had a single study each. The findings from these other comparisons were not enough to be able to decide on their effectiveness. The included studies did not mention if there were any harmful effects of the different interventions. The level of belief we have in these findings is very low. This was due to high risk of bias and the small number of people studied in the included trials. We do not have enough evidence to say which intervention works better to increase acceptance of local anaesthetic in children and adolescents. We suggest that more well-conducted studies should be done in this area.
In November 2016, we searched for clinical trials looking at psychological therapies in patients with incurable cancer receiving cancer treatment. We found 14 small studies of very low quality reporting data on tiredness outcomes, 12 of which provided data for analyses. A limited number (three studies) reported results about side effects; these studies investigated a psychological therapy combined with medication. Review authors found no support for the effectiveness of psychological therapies in reducing tiredness when assessed directly following the intervention. Very low-quality evidence suggests that psychological therapies may improve physical functioning directly after the intervention and may improve tiredness at first follow-up. Evidence shows no support for the effectiveness of psychosocial therapies in improving other domains of functioning. Limited evaluation of potential harm suggests no differences in side effects between patients receiving psychological therapy and those given usual care. Limited good quality evidence allows no conclusions on the use of psychological therapies in people with incurable cancer. Larger, high-quality trials are needed to find out whether psychological therapies help reduce tiredness for people with incurable cancer during cancer treatment. We rated the quality of study evidence using four levels: very low, low, moderate, and high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. Included studies had design problems and included a very small number of participants. Therefore, the quality of the evidence in this review is very low, and results of this review should be interpreted with caution.
We included 22 randomized controlled trials (RCTs) (total of 2761 participants). Eleven trials compared the use of fluconazole to placebo or no antifungal treatment. Three trials compared ketoconazole versus placebo. One trial compared anidulafungin with placebo. One trial compared caspofungin to placebo. Two trials compared micafungin to placebo. One trial compared amphotericin B to placebo. Two trials compared nystatin to placebo and one trial compared the effect of clotrimazole, ketoconazole, nystatin and no treatment. The RCTs included participants of both genders with a wide age range and severity of critical illness. The evidence is current as of February 2015. Funding sources from drug manufacturers were reported in 11 out of 22 studies. Another study was funded by a government agency. Results of 19 from 22 randomized trials involved 2374 participants and showed that antifungal medications given before definitive diagnosis of fungal infection did not reduce mortality from all causes. None of the studied drugs were associated with a significant reduction of mortality from all causes. However, results from 17 randomized studies involving 2024 participants showed that antifungal drugs significantly reduced the risk of developing invasive fungal infections. We also reviewed the evidence from five trials (662 participants) about the effect of antifungal treatment on the development of superficial fungal infections but we did not find any significant difference. However, we found evidence from 12 trials (1020 participants) of a significant reduction of fungi in body sites (excluding blood) not causing an infection. Eleven trials (1691 participants) reported serious adverse events requiring cessation of therapy. We found no evidence of differences in serious adverse events requiring interruption of antifungal medications between people who received and those who did not receive them. The quality of evidence for the outcome of mortality (all-cause) was moderate due to limitations in study design. The quality of evidence for the outcome of invasive fungal infection, superficial fungal infection, fungal colonization and adverse events requiring cessation of therapy was low due to limitations in study design, non-optimal total number of patients studied and results inconsistent across studies. There is moderate quality evidence that the use of antifungal treatment given before definitive diagnosis of fungal infection is not associated with a significant reduction in mortality from all causes among critically ill adults and children with a normal number of neutrophils in the blood. This type of antifungal treatment may be associated with a reduction of invasive fungal infections but the quality of evidence on this point is low. Further studies with high-quality design are needed to improve the evidence.
The evidence on which this review is based was up to date as of 17 June 2013. Six trials were included with a total of 1162 participants. All six of these trials compared the use of antibiotics to prevent infection (failures and complications) with no treatment or treatment with a placebo (a fake medicine with no active ingredient). The antibiotic used in all the trials was amoxicillin; doses and timing of doses varied, although most used a single dose taken just before the implant was placed. One of the trials, with 100 participants, also looked at different doses of amoxicillin taken at different times. There were no trials that looked at alternative antibiotics. Participants were people over 18 years of age who were able to give consent to taking part in a medical trial. Potential participants were excluded for a variety of reasons that included: if they were at risk of heart disease, had artificial joints, had problems with their immune system, were affected by diabetes, had received radiotherapy in the head and neck area, had need of additional procedures at the time of implant placement, were allergic to penicillin, had chronic/acute infections near the planned implant site, were already receiving antibiotic treatment for any other reasons (or had taken them up to six months previously), had been treated with or were receiving intravenous amino-bisphosphonates, were pregnant or breast feeding, were receiving long-term nonsteroidal anti-inflammatory drug therapy, or had blood clotting problems. The follow-up period in all the trials was at least three months. It appears that the oral administration of two grams of amoxicillin one hour before placement of dental implants is effective in reducing implant failures. More specifically, giving antibiotics to 25 people will avoid one person experiencing early implant losses. It is still unclear whether postoperative antibiotics are beneficial, or which antibiotics work best. The evidence from the six trials (1162 participants) that compared the use of antibiotics with placebo or no treatment was considered to be of moderate quality. However, the one trial (100 participants) that investigated antibiotics given for different lengths of time was found to be at high risk of bias.
We found 8 studies involving 1308 women. (We included studies up to 28 February 2015.) All the studies were randomised and involved women with low-risk pregnancies. Using ECV around 36 weeks or more increased the chance that babies were born head-first and reduced the risk of having a caesarean section. There were no clear differences in other outcomes such as the risk of babies dying. The quality of the studies and therefore the strength of the evidence was varied. If an unborn baby is lying bottom-down, turning it by ECV just before birth can reduce some of the problems this position can cause. These studies are too small to show if ECV is safe to use in women with low-risk pregnancies, however other types of studies suggest that it is safe. We also do not know if it should be used in high-risk cases, such as mothers who have already had a caesarean section, or who are expecting twins. A visual summary of some of the results from this review can be found here.
We searched the literature from 1966 to 2013 for relevant studies (randomised controlled trials only). We included five studies (involving 360 children and adults) that compared antibiotics given before the insertion of the CVC with no antibiotics before insertion. We found that giving an antibiotic before inserting a tunnelled CVC did not prevent Gram positive catheter-related infections. We included six studies (involving 468 people, mainly children) that tested flushing or locking the newly inserted CVC with a combination of an antibiotic and heparin compared with heparin only. We found that flushing the catheter with a solution containing an antibiotic and heparin reduced the number of catheter-related infections. This practice is most likely to be of value where the risk of such infections is high. We considered this evidence to be of a moderate quality.
This review (six studies involving a total of 375 participants) identified no research evidence to suggest that alginate wound dressings are more effective in healing diabetic foot ulcers than other types of dressing. More, better quality research is needed.
Children experience pain after surgery (‘postoperative pain’) and according to recently published trials the management of this pain is of major concern. A combination of drugs may be the best way to treat postoperative pain, for example drugs called ‘opioids’, like morphine and codeine. However, there are concerns about severe side effects (adverse events) when using opioids. Tramadol is a weak opioid that is used worldwide to treat children with moderate to severe acute or chronic pain. Tramadol can be given to children before surgery to help reduce pain afterwards. It is believed that tramadol administration might be associated with a lower risk for respiratory or haemodynamic depression and might therefore be the ideal analgesic drug for children in the perioperative period. Our systematic review assessed the efficacy and adverse events of tramadol administration compared to placebo or other opioids. In July 2014 we found 20 small randomised controlled trials involving 1170 patients. These small trials had limited data but tramadol may be better than placebo. In five trials, mostly preschool children undergoing minor surgery (for example tonsillectomy) were treated with tramadol or placebo before the start of surgery. Children needed less rescue medication in the postoperative care unit when given tramadol, indicating better analgesia with tramadol. Due to the low amount of usable data, the evidence focusing on the comparison of tramadol with other opioids (for example morphine, nalbuphine, pethidine, fentanyl) is currently unclear. Adverse events were generally only poorly reported in the trials so that the side effects as a result of tramadol administration were not clear.
We searched for evidence from randomised controlled trials in August 2016. We identified 11 trials that involved 638 pregnant women. They were conducted in middle-or high-income countries. We judged the overall risk of bias in the trials as unclear because of a lack of information about how the trials were conducted. Using GRADE, the quality of the evidence from the trials ranged from high to low quality. The main reasons for downgrading the quality were for risk of bias in the trials and imprecise effect sizes, low event rates and small numbers of participants. For the mothers, exercising did not appear to reduce the risk of pre-eclampsia as the measure of hypertensive disorders of pregnancy (two trials, 48 women, low-quality evidence), birth by caesarean section (five trials, 316 women, moderate-quality evidence), or the risk of induction of labour (one trial, 40 women, low-quality evidence). The mothers had similar body mass index at follow-up in the exercise and control groups (three trials, 254 women, high-quality evidence). Exercising was associated with lower fasting blood glucose levels (four trials) and blood glucose levels after a meal (three trials) but with variations in effect sizes between the different trials. The exercise programmes varied between trials as did their duration and whether or not they were supervised. None of the included trials reported on perineal trauma, postnatal depression or development of type 2 diabetes. For the babies, no deaths occurred around the time of birth in (one trial, 19 babies, low-quality evidence) and there was no evidence of any difference in the risk of ill-health (two trials, 169 babies, moderate-quality evidence) or low blood sugar levels (one trial, 34 babies, low-quality evidence). None of the trials reported on the number of large-for-gestational-age babies or babies that went on to develop diabetes in childhood or adulthood or neurosensory disability that became apparent during childhood. Although exercise appeared to be able to lower fasting blood sugar levels and sugar levels after a meal, we did not find any differences in other outcomes for pregnant women with GDM. The present evidence is insufficient to advise for or against women enrolling in exercise programmes. Even if exercise does not provide any benefit during pregnancy, this change in lifestyle may persist after birth and may help prevent the onset of type 2 diabetes and its long-term complications. Pregnant women with GDM who wish to enrol in an exercise programme may wish to discuss their choice with a health professional. Further research is needed comparing one exercise intervention with another (or with a control) and reporting on both the short- and long-term outcomes (for both the mother and infant/child/adult) as listed in this review.
We searched for study reports and found 19 randomised or quasi-randomised controlled trials including 1190 participants overall that assessed the safety and benefit of splinting for people with CTS. The risk of bias of studies was low in some studies and unclear or high in others. One low quality study suggests that splinting at night leads to more overall improvement in the short term when compared to no treatment, but we cannot say from the evidence whether one splint design or wearing regimen is more effective than another, nor can we say that splinting is more effective than other non-surgical interventions for CTS (for example exercises, oral steroids). Nine trials measured adverse effects of splinting and all found either no or few participants reported discomfort or swelling due to splinting. More research is needed to find out how effective and safe splinting is for people with carpal tunnel syndrome, particularly in the long term.
This updated review includes 51 trials: 18 trials contrasted manipulation or mobilisation against no treatment or pretend treatment; 34 trials compared manipulation or mobilisation against another treatment (electrotherapy, exercise, medication) and various techniques or dosages. [Note one trial included two comparison groups]. Although other reviews focusing on adverse events suggest that mobilisation is safe and manipulation may result in rare but serious side effects such as stroke, disc herniation or serious neurological deficits, our review noted temporary and benign side effects with both approaches; more than half of the included trials did not report on adverse effects. • Manipulation or mobilisation versus inactive treatment: For subacute/chronic neck pain, a single manipulation produced temporary pain relief. However, conflicting evidence was found at short-term follow-up for pain reduction with multiple sessions. At short-term and intermediate-term follow-up, multiple sessions of thoracic manipulation were favoured for pain reduction among participants with acute/subacute neck pain, and for functional improvement among those with acute to chronic neck pain. No additional pain relief was reported when thoracic mobilisation was used. • Manipulation or mobilisation versus another active treatment: Cervical manipulation produced changes in pain, function, quality of life, global perceived effect and patient satisfaction that were comparable with those attained with cervical mobilisation up to intermediate-term follow-up for patients with neck pain of any duration. Cervical manipulation for acute/subacute neck pain was more effective than varied combinations of analgesics, muscle relaxants and non-steroidal anti-inflammatory drugs for improving pain and function at up to long-term follow-up. For chronic cervicogenic headache, cervical manipulation provided greater benefit than light massage in improving pain and function at short-term and intermediate-term follow-up. For chronic CGH, cervical manipulation may be superior to transcutaneous electrical nerve stimulation (TENS) in improving pain at short-term follow-up. For acute neck pain, cervical manipulation may be more effective than thoracic manipulation in improving pain and function up to intermediate-term follow-up. Finally, for subacute and chronic neck pain, cervical mobilisation appeared similar to pulsed ultrasound, TENS, acupuncture and massage in improving pain, function, quality of life and patient satisfaction up to intermediate-term follow-up. However, combining laser with manipulation may be superior to using manipulation or laser alone. No high-quality evidence was found, so uncertainty about the effectiveness of mobilisation or manipulation for neck pain remains. Future research is likely to have an important impact on the effect estimate. Authors of this review encountered many challenges, for example, the number of participants in most trials was small, 80% (41/51) of the included studies were of low or very low quality and evidence on the optimum dosage requirement was limited.
Study characteristics: We included 27 trials, 18 of which were conducted in the USA. Fifeteen trials tested strategies to implement healthy eating policies, practice or programs; six trials tested strategies targeting physical activity policies or practices; and three trials targeted tobacco policies or practices. Three trials targeted a combination of health behaviours. None of the included trials sought to increase the implementation of interventions to delay initiation or reduce the consumption of alcohol. The trials tested a range of implementation support strategies, including educational materials, educational meetings, the use of opinion leaders, external funding, local consensus processes, and tailored interventions. Search date: The evidence is current to 31 August 2016. Key results: It is uncertain whether the strategies tested improve implementation of the targeted school-based policies or practices, student health behaviours, or the knowledge or attitudes of school staff. It is also uncertain whether the strategies tested result in unintended adverse effects or whether they are cost-effective. Limitations: Trial heterogeneity, and the lack of consistent terminology describing implementation strategies were important limitations of the review. Quality of evidence: We rated the overall quality of evidence as very low for all outcomes that included trial-reported effects.
Only a single multi-centre study could be included in this review. Evidence is current to January 2014. This study was funded by the National Health and Medical Research Council of Australia. This study of 272 children in five Australian hospitals reported that those randomly assigned to earlier treatment according to a clinical pathway showed improved clinical outcomes (cough resolved earlier and quality of life was better) compared with those who were randomly assigned to later use of the pathway. No adverse events were reported. The quality of evidence was graded as moderate. Evidence is limited, as only one study could be included in this review. This study was unable to completely blind participants to the clinical pathway.
This overview summarised the evidence from 75 systematic reviews on consumers' medicine use published to March 2012. Reviews covered acute and chronic diseases in diverse populations and settings; and evaluated a wide range of strategies to improve medicines use, including support for behaviour change, risk minimisation and skills acquisition. Medicines adherence was the most commonly-reported outcome, with others such as knowledge and clinical outcomes also reported. Adverse events were identified less often. Collectively, the results suggest that there are many different potential pathways through which consumers' use of medicines could be targeted to improve outcomes. However, no single strategy improved all medicines-use outcomes across all diseases, populations or settings. Strategies that appear to improve medicines use include medicines self-monitoring and self-management programmes, while simplified dosing regimens and directly involving pharmacists in medicines management (eg medicines reviews) appear promising. Other strategies, such as delayed antibiotic prescriptions; practical management tools (eg reminders, packaging); education or information combined with other strategies (eg self-management skills training, counselling); and financial incentives, may also have some positive effects, but their effects are less consistent. Some strategies, such as directly observed therapy, may be ineffective. Other strategies such as providing information or education alone may have variable effects, being ineffective to change some outcomes (eg medicines adherence) but improving others such as knowledge, which is key for informed medicines choices. Despite a doubling of the number of included reviews in this update, uncertainty remains about the effects of many interventions, and the evidence on what works was particularly sparse for several populations, including children and young people, carers, and people with multimorbidity. Included reviews often had methodological limitations - at study level, review level, or both - meaning results should be interpreted with caution.
The evidence was current to May 2013. An intervention could be delivered in a group setting (group intervention), as one to one contact between a therapist and a patient (individual intervention) or in the form of couple therapy where the patient and her spouse attends the therapy sessions (couple intervention). The control group could receive educational leaflets or have access to seminars or relaxation classes. A comprehensive search of the literature was conducted and 28 studies comprising 3940 participants were included. The majority (24 out of 28 studies) of interventions were based on cognitive behavioural therapy, which involves changing a person's thoughts and behaviour. Four studies used psychotherapy as the intervention. Generally, the methods for assessing outcomes (such as anxiety, depression, quality of life) after the intervention and the timing of these assessments were not uniform across studies. Women who received cognitive behavioural therapy showed important reductions in anxiety, depression and mood disturbance, especially when it was delivered to groups of women. An improvement in quality of life was observed when women received individual cognitive behavioural therapy compared to the control group. The effects on survival were uncertain because the results were imprecise. The four psychotherapy studies reported limited information for each outcome. Therefore no firm conclusion could be made about the efficacy of psychotherapy. Adverse events were not reported in any of the included studies. Further research should aim to provide evidence for people to make informed decisions about whether the effects of these treatments are sustainable after discontinuation of the therapy. The quality of evidence ranged from very low quality (for example for quality of life, individually delivered intervention) to moderate quality evidence (for mood disturbance). The interventions varied between studies as did the methods and timing of outcome measures and treatment received within the control groups.
We found six randomised controlled trials and three observational studies that assessed the effects of HAART plus chemotherapy compared with HAART alone; HAART plus chemotherapy compared with HAART plus another chemotherapy regimen; and chemotherapy compared with chemotherapy in the time before HAART was available. Of the nine included studies, seven included patients with a mix of mild to moderate (T0) Kaposi's sarcoma and severe (T1) Kaposi's sarcoma. There was no universal definition for what severity of disease was considered chemotherapy-requiring. For this review, we only extracted data for 792 HIV infected adults with severe Kaposi's sarcoma disease. The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, in choosing among different chemotherapy regimens, there was no observed difference between liposomal doxorubcin, liposomal daunorubicin, and paclitaxel. The overall quality of evidence in this review can be described as moderate.
We searched for studies on 10 August 2015 but did not find any randomised controlled trials looking at the effects of performing extra tests on health outcomes in pregnant women with overgrowth of the baby after 20 weeks gestation. There is a need for randomised controlled trials in this area in order to inform clinical practice when large babies are identified during a pregnancy, to assess if extra tests or surveillance can improve the health of these women and their babies. It is also important to identify any harms associated with extra tests and surveillance, as identifying women with suspected large babies may lead to unnecessary maternal anxiety with additional investigations and interventions, including induction of labour or caesarean section.
This review aimed to assess the effectiveness of all current treatments for people with delusional disorder. A search for randomised controlled trials was run in 2012. Authors found 141 citations in the search but only one trial, randomising 17 people, could be included in the review. The study compared the effectiveness of CBT with supportive psychotherapy for people with delusional disorder. Participants were already taking medication and this was continued during the trial. The review was not able to include any studies or trials involving medications of any type used to treat delusional disorder. For the study that was included, there was limited information presented that we could use. Firm conclusions were difficult to make and no evidence on improving people's behaviour and overall mental health was available. More people left the study early from the supportive psychotherapy group, but number of participants was small and the overall difference between the groups was not enough to conclude one treatment was better than the other. A positive effect for CBT was found for people's social self esteem, although again, this finding is limited by the low quantity and quality of the data and does not relate to people's social or everyday functioning. Currently there is an overall lack of high quality evidence-based information about the treatment of delusional disorders and insufficient evidence to make recommendations for treatments of any type. Until such evidence is found, the treatment of delusional disorders will most likely include those that are considered effective for other psychotic disorders and mental health problems. Further large-scale and high quality research is needed in this area. Research could be improved by conducting trials specifically for people with delusional disorder. Ben Gray, Senior Peer Researcher, McPin Foundation: http://mcpin.org/.
The Information Specialist of the Cochrane Schizophrenia Group searched the specialised register in October 2015. He ran an electronic search for trials that randomised people with schizophrenia to receive either bifeprunox or placebo, finding 42 records. The review authors screened these for inclusion in the review. Only four trials provided useable data, and these were of poor quality with some evidence of missing data. Two trials are completed but not yet published; we could not obtain any information from these trials that we could use in this review. The data available to us showed that bifeprunox improved participants' scores on both positive and negative symptom scales. Weight increase was similar between those receiving bifeprunox and those allocated to placebo. Data regarding the effects of bifeprunox are scarce. The data we found, which were of poor quality, showed no real evidence that bifeprunox is unsafe or ineffective. Its effects do not seem significantly different to other drugs that are currently on the market. More data on this compound exists but is not publicly available. We believe that the licencing authority in the USA must have had more information on which to base their important decision. The drug company also seemed to lose the will to move forward with bifeprunox. Whether or not the decision to prohibit access to a potentially useful drug was taken because of clear evidence of adverse effects, market calculations, or biases, it would seem an omission that all information upon which this decision was made is not in the public domain.
We could only include one small study in the review (14 participants) and this was stopped early because not enough people agreed to join the study as volunteers. The study lasted six months and compared omalizumab (Xolair®) injections under the skin of the upper arm or the thigh to placebo injections (dummy treatment containing no active medication). Volunteers were given of 600 mg of omalizumab or placebo daily along with itraconazole (an antifungal drug) twice daily and oral corticosteroids, with a maximum daily dose of 400 mg. The full results of the study were not published. Only limited results on side effects were published online. Six out of nine volunteers (66.67%) in the omalizumab group and one out of five volunteers (20%) in the placebo group reported one or more serious side effects. Due to the lack of evidence, we are not able to make recommendations either in favour of, or against the use of, anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. More research into this treatment is needed.
We included eight studies with 11,164 participants but one study did not provide enough data to be useful. One study from Africa found a strong increase in uptake of Voluntary Counseling and Testing (VCT) to 51% when delivered on-site which was 14 times more compared to a voucher for off-site testing. However, VCT did not change HIV incidence in one study among African factory workers. In another study among HongKong truck drivers, VCTdecreased self-reported sexually transmitted diseases (STD) but VCT did not decrease unprotected sex significantly. Education was studied among soldiers in Nigeria, Angola and the US, truck drivers in India and factory workers in Thailand.. Education that was modelled after a motivational theory reduced STDs with 32%, decreased unprotected sex with a small amount, reduced sex with a commercial sex worker with 12% but did not decrease the number of partners or the habit of using alcohol before sex. We concluded that workplace interventions for preventing HIV are feasible and that it is possible to study them in a randomised controlled trial. Peer influence has a positive effect on VCT uptake and workplace interventions can change risky sexual behaviour to a moderate degree. More randomised trials are needed in high risk groups or in areas with high HIV prevalence to find more effective interventions.
We found seven randomised trials involving 138 participants, which provided data on 123. All were male, aged between 16 and 68 years. Offending ranged from very serious (e.g., rape) to minor criminality (e.g., exhibitionism). Comparators included placebo (five studies), psychological treatment (one study), and a combination of psychological and pharmacological treatment (one study). Five studies took place in the community and two in a secure hospital. Duration varied between three and 13 months. Six studies examined the effectiveness of three testosterone-suppressing drugs: cyproterone acetate (CPA), ethinyl oestradiol (EO), and medroxyprogesterone acetate (MPA). In two of these studies, MPA was given alongside a psychological therapy (assertiveness training or imaginal desensitisation). The seventh study assessed the effectiveness of two antipsychotics (benperidol and chlorpromazine) versus placebo. Meta-analysis was not possible due to heterogeneity of interventions, comparator groups, study designs, and other issues. Two studies reported reoffending rates formally. One trial of intramuscular MPA plus imaginal desensitisation (ID) found no reoffending at two-year follow-up for the intervention group (n = 10 versus one relapse within the group treated by ID alone). A three-armed trial of oral MPA, alone or in combination with psychological treatment, reported a 20% rate of reoffending amongst those in the combined treatment arm (n = 15) and 50% of those in the psychological treatment only group (n = 12). Notably, all those in the 'oral MPA only' arm (n = 5) dropped out immediately, despite treatment being court mandated. Two studies did not report reoffending rates as they both took place in a secure psychiatric facility from which none were discharged. Three community studies did not formally report reoffending at all, focusing largely on 'abnormal sexual activity'. Secondary outcomes: Studies reported a variety of secondary outcomes. Results suggested that the frequency of self reported deviant sexual fantasies may be reduced by testosterone-suppressing drugs, but not the deviancy itself. Where measured, hormonal levels, particularly levels of testosterone, tended to correlate with measures of sexual activity and anxiety. One study measured anxiety formally; one study measured anger/aggression. Adverse events: Six studies provided information on adverse events and none tested the effects of testosterone-suppressing drugs beyond six to eight months. The most severe were reported in a trial of antipsychotic medication. Reported side effects in two trials of oral MPA and CPA included considerable weight gain. Side effects of intramuscular MPA led to discontinuation in some participants. Important increases in depression and excess salivation were reported in one trial of oral MPA. No deaths and no suicide attempts were reported in any study. We conclude that these seven trials (published more than 20 years ago), examining only a limited number of drugs, provide a poor evidence base to guide practice. Not only were the trials small, they were of short duration, included varied participants, and none trialled the newer drugs currently in use, particularly SSRIs or GnRH analogues. The results of this review, therefore, do not allow firm conclusions to be drawn regarding pharmacological interventions as an effective intervention for reducing sexual offending. New studies are needed that address these deficits. Data should also be collected on the characteristics of those who refuse, drop out, and complete treatment. Overall, the quality of the evidence was poor. We had concerns about: number of participants leaving studies, blinding of those who measured outcomes, ways in which investigators concealed allocation of treatment to those delivering it, and reporting of our primary outcome: reoffending.
We found two randomized controlled trials (95 adult participants) and one non-randomized controlled study (17 children aged at least four weeks) conducted in Portugal, Canada, and the United States. We rated the two randomized trials as being of unclear quality and the non-randomized study as being low quality. The largest randomized trial (75 participants) found a 83% success rate for extubation with mechanically- and manually-assisted cough used in combination, compared with 53% in the control group (extubation success over 1½ times more likely) (very low-quality evidence). The time spent on a ventilator was six days less in people using mechanically- and manually-assisted cough (very low-quality evidence). No participants died in this trial. Complications were reported by the two randomized trials. One person receiving mechanically-assisted cough experienced a prolonged drop in blood pressure; another person receiving breathstacking and suctioning in addition to manually-assisted cough experienced a prolonged rise in blood pressure. In one trial, following removal of the breathing tube, more people in the group not receiving mechanically-assisted cough experienced secretion retention, a drop in oxygen levels, and needed the breathing tube to be reinserted (nine people compared with two, very low-quality evidence). The non-randomized study reported that the breathing tube could be removed in all of the six children in the group receiving interventions to assist with coughing. In this non-randomized study, death was only reported for children receiving a cough-promoting technique. One child died, but this was not thought to be related to the cough technique. This study did not report adverse events associated with assisted coughing. No included study evaluated a single cough-promoting technique in isolation. The two randomized trials combined manually-assisted cough with either mechanical assistance (MI-E) or breathstacking, and the non-randomized study used all three methods. Very low-quality evidence from single trial findings suggests that cough-promoting techniques might increase successful removal of the breathing tube and decrease the time spent on mechanical ventilation, while not causing harm. The limited participant numbers made it difficult to determine the likelihood of harms.
The review authors searched the medical literature for randomised controlled trials to inform the most appropriate surgical techniques to use. Twenty-seven trials involving 17,808 women from a number of different countries contributed to the review. None of these trials assessed the type of uterine incision (side to side (transverse) lower uterine segment incision versus other types of uterine incision). Results from 18 randomised trials contributed to reports that single layer closure of the uterine incision was associated with a reduction in blood loss, and duration of the procedure. In these studies the surgical procedure for entering the abdominal cavity also differed and could have contributed to blood loss and duration of surgery. Five trials compared blunt with sharp dissection at the time of the uterine incision (2141 women) and a further two trials auto-suture devices with standard hysterotomy (300 women). Blunt surgery was associated with a reduction in mean blood loss at the time of the procedure. The use of an auto-suture instrument did not clearly reduce procedural blood loss but increased the duration of the procedure. Overall, trials focused on blood loss and duration of the operative procedure rather than clinical outcomes for the women. The methodological quality of the trials was variable.
Anticoagulants are more effective than antiplatelet drugs to prevent a second stroke in people with atrial fibrillation. Nonrheumatic atrial fibrillation (NRAF) is a heart rhythm disorder commonly found in patients who have had a stroke. Patients with NRAF have an irregular heart beat. This can cause the formation of a blood clot in the left atrium of the heart. This clot may break away and block a cerebral artery, thus causing a stroke. Patients who have had a stroke in the presence of NRAF have a high risk of another stroke. Anticoagulant drugs, such as warfarin, make the blood 'thinner' and prevent the formation of blood clots and hence could prevent stroke. However, anticoagulant drugs may also cause bleeding in the brain and this complication could offset any benefits. Aspirin may be a safer alternative. This review identified two trials in which patients with NRAF who had a stroke were treated with anticoagulants or antiplatelet therapy. These studies show that anticoagulants are superior to antiplatelet agents to reduce the risk of recurrent stroke.
Although this research reports that  positive gains have been reported from a case-based study of a child with dysarthria following ABI (specifically with traumatic brain injury), there are currently too few studies performed in this area to draw any conclusions about the efficacy of treatment for dysarthria in children and teenagers. This review therefore calls for Speech Language Pathologists/Speech Language Therapists (SLPs/SLTs) working in this area to perform studies of the natural history and treatment efficacy of this group.
We found three trials that studied two different TCAs - clomipramine and tianeptine. One of the clomipramine studies involved children and young adults; the other two studies enrolled only children. All three trials were small, with between 12 and 32 participants. There is only limited evidence to support the use of clomipramine or tianeptine in the treatment of individuals with ASD, and some evidence of side effects that would limit their usefulness. Clinicians considering the use of TCAs in ASD need to be aware of the limited and conflicting evidence of effect and the side effect profile of TCAs when discussing this treatment option with patients with ASD and their carers. More research is required before TCAs can be recommended for use in ASD.
The review authors searched the medical literature and found six controlled studies in which patients were randomized to primary repair or fecal diversion. Results were reported for a total of 705 patients. The two groups sustained significant injuries with the primary repair patients at least as ill as the diverted patients. The studies were reported from 1979 to 2002 and involved increasingly 'high risk' patients. Five were conducted in the United States and one in South Africa. Primary closure was at least as safe as fecal diversion. The number of deaths was similar in both the primary repair (1.94%) and the diverted groups (1.74%). Total complications, total infectious complications, abdominal infections and wound complications all favored primary repair. The studies did not adequately report colostomy closure for trauma-related colostomies, which can itself result in complications and significant illness.
We included three studies with a total of 112 participants. Participants were randomly assigned to singing training or to a non-singing control group. The control groups were either a film workshop, handcraft work, or nothing at all. The singing was performed in groups, once to twice a week for one hour, for a minimum of six weeks. There was diversity in the results of the studies and we were unable to combine many results in 'meta-analyses'. A meta-analysis is a statistical analysis which combines the results of two or more separate studies to give a pooled result. Some studies showed improvements in some aspects of quality of life, while others showed no improvement. Breathlessness was only measured in one study and no improvement was found. The studies did not report whether any effects lasted for a long time after the singing training was completed. No studies reported any side effects from singing, so singing appears to be safe for people with COPD. The studies were of low quality due to the small number of participants and missing information about the methods and some of the outcomes. We were unable to find enough evidence to sufficiently determine the effect of singing in people with COPD. More studies are required and they should concentrate on enrolling larger numbers of people.
We found one trial (238 people took part) comparing ataluren to placebo (a dummy treatment with no active medication). The trial lasted 48 weeks and included both males and females aged six years and older. Everyone taking part had at least one copy of a nonsense mutation (a type of class I mutation that causes cystic fibrosis). In those people who took ataluren, there was no improvement in clinical outcomes such as quality of life, lung function, exacerbations (flare up of disease), sweat chloride (salt) levels or weight. The trial found that kidney damage was more common in people who took ataluren. The trial investigators then analysed the results in a way that they hadn't planned originally and looked at how ataluren or placebo affected people depending on whether they were using inhaled tobramycin on a long-term basis or not. They found that amongst those not taking inhaled tobramycin, lung function declined at a slower rate and there were fewer exacerbations in the ataluren group compared to the placebo group. We have not found enough high-quality evidence currently to determine the effect of ataluren for treating people with cystic fibrosis. We recommend that future trials are designed and reported clearly so that their results can be included in a systematic review. We judged the quality of the evidence was moderate with uncertainty due to how widely the results varied between participants. We are satisfied that everyone taking part had an equal chance of being in either group (ataluren or placebo) and that no one could work out which group the next person would be put into, so that healthier people did not receive the treatment and make the results seem better. We believe that the clinicians running the trial and those taking part in the trial did not know which treatment each person was receiving. We have some concerns on the emphasis the investigators have placed on the results of a comparison they had not planned (use of long-term inhaled tobramycin). Unfortunately, the trial did not report all their results clearly; sometimes they did not report them in a way that we could use in the review and sometimes they did not report the data at all. This affected the certainty with which we judged the overall results. The trial was sponsored by PTC Therapeutics Incorporated. The Cystic Fibrosis Foundation, the Food and Drug Administration's Office of Orphan Products Development and the National Institutes of Health (NIH) also supported the trial.
We searched for studies up to March 2014. We found 10 studies, including four randomised controlled trials and 6 cohort studies collecting data from HIV care programmes. All the studies were conducted in Africa in adults who were followed up for up to one year. We describe three types of care: - Doctor versus nurse or clinical officer care for initiation and maintenance of antiretrovirals - Doctor versus nurse or clinical officer care for maintenance of antiretroviral therapy - Doctor versus community health workers for maintenance of antiretroviral therapy. We found high quality evidence from trial data that when nurses initiated and provided follow-up HIV therapy, there was no difference in death and lower rates of losses to follow up at one year, (n = 2770). However, lower quality data from two cohort studies suggests that there may be an increased risk of death in the task shifting group, (n = 39 160) but no difference in patients lost to follow-up between groups, We found moderate quality evidence from two trials that when doctors initiated therapy and nurses provided follow-up, that there was probably no difference in death or number of patients lost to follow up at one year (n = 4332). Lower quality evidence from the cohort study showed that death as well as the number of patients lost to follow-up at one year may be lower in the group treated by nurses. Compared to doctor led care, we found moderate quality evidence from a single trial that when antiretroviral therapy was provided in the community, by trained field workers, there was probably no difference in death or losses to follow-up (n= 559).
Of the three prospective observational studies, one reported no survival differences between menstrual cycle groups after stratification by lymph node status at a mean follow-up of 48 months. The results showed a lack of prognostic value (recurrence-free survival and overall survival) of timing of surgery in relation to the menstrual period or to oestrogen and progesterone levels in premenopausal breast carcinoma patients. One study gave no data on mean survival time or recurrence-free survival and the third study reported no significant difference in the overall survival of patients when surgery was done in either the follicular or luteal phase of the menstrual cycle. A large randomised controlled trial would be ideal to establish the influence of timing of surgery in relation to the menstrual cycle (follicular phase or luteal phase) on the prognosis of breast cancer. However, in the absence of this, the information available from the prospective observational studies shows that there is no difference in disease-free survival and overall survival in non-metastatic breast cancer patients irrespective of whether the surgery was done during the follicular or the luteal phase.
The four RCTs were conducted in Australia, Canada, the Netherlands and USA, and involved 192 parents. Each studied a different intervention and considered different outcomes. All but seven of the participating parents were mothers. Children's ages ranged from one month to six years and five months. Three interventions were delivered at home, and one in a community venue (e.g. a church). Interventions varied in duration from seven weeks to 12 months. They included a range of practical childcare skills, home safety and developing parents' ability to respond sensitively to their children. Parents in the control groups all received treatment as usual. Each study was sponsored by different funders. One study was funded by the Ontario Mental Health Foundation and the Ontario Ministry of Community and Social Services Research Grants Program. Another was funded by the Alabama Development Disabilities Council. A third was funded by the Best Practice Parenting Education Initiative of the Commonwealth Department of Family and Community Services and the New South Wales Aging and Disability Department. The fourth study was funded by ZonMw, The Netherlands Organisation for Health Research and Development. Compared to those parents without parent training, the studies reported some improvements in parents in the intervention group. One study reported improvement in safe home practices, recognition of child illness and safe use of medicines, in favour of the intervention group. Another study reported improvements in childcare and safety, also in favour of the intervention group; and a third study found that parents who had attended parent training reported less child-related parenting stress compared to the control group. A fourth study reported improvement in mother-child interaction in the intervention group compared with the control group. No study reported that interventions caused harm. The quality of the evidence ranged from very low to moderate. There is some low-quality evidence that parent training interventions for parents with intellectual disabilities may support their parenting. It may also help to establish good parent-child relations. However, given the low quality of the evidence, the results should be interpreted with caution. Better-quality research is needed to evaluate the effectiveness of parent training interventions for parents with intellectual disabilities. These studies should include fathers and follow-up participants over a longer time period.
We conducted a search to identify evidence published before September 2017. Studies were eligible for inclusion if they compared automated sepsis monitoring to standard care (such as paper-based systems) in people admitted to intensive or critical care units for critical illness. We did not include non-randomized studies (studies where participants were not allocated to treatment groups by chance), quasi-randomized studies (studies where participants were allocated to treatment groups by a method that is not truly down to chance, such as date of birth or medical number), and cross-over studies (where participants first receive one treatment and then cross over to receive the other treatment). Studies including people already diagnosed with sepsis were also excluded. We included three randomized controlled trials (studies where participants were allocated to treatment groups by chance), involving 1199 participants in this review. Overall there were no significant differences in time to start of antimicrobial therapy (such as antimicrobial and antifungal treatments, very low-quality evidence), length of stay in the intensive care setting (very low-quality evidence), or in mortality at 14 days, 28 days or discharge (very low-quality evidence) when automated monitoring systems were compared to standard care. Very low-quality evidence was available on failed detection of sepsis but data reporting was too unclear to enable us to analyse this in a meaningful way. Other outcomes that we wished to assess like time to initiation of fluid resuscitation (the process of increasing the amount of fluids in the body), mortality at 30 days, and quality of life were not reported in any of the studies. Results of this review show limited, very low-quality evidence, which has prevented us from drawing meaningful conclusions. It is unclear what effect automated systems for monitoring sepsis have on any outcomes included in this review, and therefore we are uncertain if automated sepsis monitoring is beneficial or not. Additional, high-quality evidence is needed to help address our review question.
We found five studies involving 168 participants with painful diabetic neuropathy or polyneuropathy. Studies were randomised and double-blind, but all had one or more sources of potential major bias that could lead to overestimation of efficacy. It was not possible to combine information from the different studies, but individually they indicated some benefit from imipramine (usually at a dose between 100 mg and 150 mg daily) compared with placebo, at the expense of increased adverse events. There was too little information, which was of inadequate quality, to be sure that imipramine works as a pain medicine in neuropathic pain due to diabetes or due to damage to multiple nerves. There was no information about other types of neuropathic pain. Other medicines have been shown to be effective.
We included randomised controlled trials that compared antibiotics with a placebo (pretend treatment) or control group. The children included in the trials had wet cough lasting more than 10 days. The evidence is current to September 2017. We found three studies that varied in a number of ways including different antibiotics (two studies used amoxicillin/clavulanate acid and one used erythromycin) and length of treatment was seven or 14 days. The mean ages of the children ranged from 21 months to six years. This review, involving 190 children with persistent wet cough, found that antibiotics were beneficial in curing the cough. The cure rate was one child cured for every three children treated. Antibiotics also prevented the illness from getting worse, thus avoiding a further course of antibiotics, for one in every four children treated. We found no clear evidence about whether antibiotics were associated with more side effects. We could not assess long-term results. The reliability of the evidence was moderate when using antibiotics to cure cough and for illness progression, while it was only low for side effects of medicines. Antibiotics are effective in treating children with chronic (greater than four weeks) wet cough and could be considered when they present to doctors.
We found 15 randomised controlled studies involving over 2000 pregnant women with urinary infections, but no symptoms. Antibiotics may be effective in reducing the incidence of kidney infection in the mother (12 studies, 2017 women) and clearing the infection from the urine (four studies, 596 women). They may also reduce the incidence of preterm births (three studies, 327 women) and low birthweight babies (six studies, 1437 babies). None of the studies adequately assessed any adverse effects of antibiotic treatment for the mother or her baby, and often the way the study was done was not well described. We assessed the three main outcomes with the GRADE approach, and found low-certainty evidence that antibiotic treatment may prevent pyelonephritis, preterm birth, and birthweight less than 2500 g. Antibiotic treatment may reduce the risk of kidney infections in pregnant women who have a urine infection but show no symptoms of infection. Antibiotics may also reduce the chance a baby will be born too early or have a low birthweight. However, because of the low certainty of the evidence, it is difficult to draw conclusions; more research is needed.
We included studies that looked at hormonal birth control use and fracture risk. We examined the quality of research methods using a tool for observational studies. With these types of studies, investigators need to control for differences in the study groups. We used the results from adjusted analyses as reported. Where we did not have adjusted analysis, we used the odds ratio to look at differences between groups. We found 14 studies. Six of them had good quality results and looked at use of birth control pills. We did not find an overall difference in fracture risk for users and nonusers of birth control pills. One study found pill users were more likely to have fractures overall. Another had later data for a subset of those women. Pill use was not related to fracture risk except for 10 or more years since use. Still another study showed more risk when the woman had 10 or more prescriptions. When a study of postmenopausal women removed the women with prior fracture, pill users did not have higher fracture risk. Two more studies saw more fractures in pill users but only for certain subgroups. Two studies looked at birth control methods that contain only the hormone progestin. They found that users of the injected ‘depo’ (depot medroxyprogesterone acetate) had more fractures as did women with longer current use. One showed more fractures for women with any past 'depo' use. Another study showed that women who had used the hormonal intrauterine device (IUD) were less likely to have a fracture. These studies did not show that birth control pills are generally related to more fractures. Some studies reported greater risk for subgroups. Users of ‘depo’ may have more fracture risk. Observational studies need to examine differences between study groups. Investigators should be clear about the factors studied in the analysis.
Endometrial cancer is cancer arising from the lining of the womb. Most women with endometrial cancer are diagnosed when their tumour is still confined to the body of the womb. However, about 10% of women with endometrial cancer are diagnosed when the disease is already at an advanced stage. The latter group of patients tend to have much poorer survival. Treatment of women with advanced or recurrent endometrial cancer is challenging because often they suffer from other diseases and aggressive chemotherapy with or without surgery may not be beneficial or may even be harmful. Hormonal therapy in these cases is thought to be easily administered and to cause fewer side effects than systemic chemotherapy (standard treatment). The purpose of this review was to assess the available literature on the effect of hormonal treatment on the survival of patients with advanced or recurrent endometrial cancer. We found six randomised controlled trials (RCTs) that assessed hormonal treatment in various forms and combinations in 542 eligible patients. We found insufficient evidence to suggest that hormonal therapy improves survival in these patients. The main limitations of the review were the small number of patients included in the RCTs, the diversity of both the patient population and the hormonal agents used and the fact that quality of life was not reported in any of the trials. The quality of life with treatment is especially important for a condition that has a poor survival rate.
This review compared the efficacy, withdrawal rates and side effects of different antidepressant classes in the treatment of depression in older people. Thirty-two studies provided data for the review. Our main findings indicate that tricyclic antidepressants (classical and tricyclic related) and selective serotonin reuptake inhibitors (SSRIs) are equally efficacious. However, when comparing the two tricyclic groups with SSRIs we found that tricyclic related antidepressants were similar to SSRIs in terms of overall withdrawal rate, and classical tricyclic antidepressants were associated with a higher withdrawal rate due to side effects. These findings are reflected in the differing side effect profiles when comparing both tricyclic groups with SSRIs. The findings of the review must be interpreted with some caution in view of the relatively low patient numbers and lack of side effect data.
We included three small randomised trials involving 149 women in preterm labour in the review. These trials were conducted in the 1950s and had a high risk of bias overall. We found no convincing evidence that relaxin (given by intravenous and intramuscular injection) can prevent preterm birth for women in preterm labour. Only one of the studies, involving 30 women (and at a high risk of bias), reported on birth within seven days of treatment and found that women who received relaxin were less likely to give birth preterm within seven days of treatment, and were more likely to have a longer pregnancy than women who did not receive relaxin. The risk of babies dying was not significantly different between the women who received relaxin and those who did not. Neither of the other two trials found clear differences in preterm birth, and no trial reported on longer-term outcomes for the babies. There is therefore insufficient evidence from this review to recommend relaxin as an intervention to prevent preterm birth for women in preterm labour.
This review included 38 randomised controlled studies, involving 3679 women. Vaginal misoprostol was as effective as other agents in inducing labour and achieving vaginal birth within 24 hours, with a reduction in the occurrence of maternal side effects. Side effects include gastrointestinal disturbance (nausea, vomiting, diarrhoea). The information on rare adverse events (including uterine rupture) is limited.
We included two studies comparing supine midline head position versus supine head rotated 90°. This review of trials found too little evidence to show positive or negative effects of supine (lying on the back) midline head position for prevention of intraventricular hemorrhage (i.e., bleeding within the brain), mortality, or any other relevant outcomes in very preterm neonates. More research is needed. We found no trials that compared supine (lying on the back) versus prone (lying on the stomach) midline head position, and no trials that compared effects of head tilting (elevating the head of the incubator upward). Results of this systematic review are consistent with beneficial or detrimental effects of a supine head midline position and do not provide a definitive answer to the review question.
The results of this review demonstrate that low dose oral cyclosporine is not effective for treatment of active Crohn's disease. Studies indicate that Crohn's patients treated with low dose (5 mg/kg/day) oral cyclosporine could experience side effects including kidney problems. Therefore the use of this medication for the treatment of chronic active Crohn's disease is not advisable. Higher oral doses and injections of cyclosporine have not been sufficiently evaluated. Larger doses of cyclosporine are not likely to be useful for the long-term management of Crohn's disease due to the risk of kidney damage and the availability of other proven medications.
The review included nine randomised controlled trials with 425 participants, comparing omega-3 fatty acid supplementation with other fatty acids. On the basis of these studies, omega-3 fatty acid supplementation did not improve walking distance, blood pressure in the leg or any other measure of clinical benefit. There was some limited evidence to suggest that omega-3 fatty acid supplementation may reduce blood viscosity (the resistance of blood to flow), which when high could potentially contribute to intermittent claudication. There was no evidence to suggest that omega-3 fatty acid supplementation reduced plasma (the liquid component of blood) viscosity or improved the levels of different types of cholesterol or any other components of blood tested. Side effects such as nausea, diarrhoea and flatulence were observed in two studies.
Researchers conducted a review of the effects of corticosteroids given in addition to antibiotics to children with septic arthritis. Evidence was sought until April 2018. After searching for all relevant studies, reviewers found two studies with 149 children. These studies were conducted in hospitalised children with a normal immune system between the ages of three months and 18 years living in Costa Rica and Israel. The longest follow-up was one year. Reviewer findings are summarised below. What is septic arthritis and what are corticosteroids?  Septic arthritis, which is more frequent in children, is a serious disease caused by bacteria that infect the joints. Patients are usually treated with antibiotics, but secondary inflammation can destroy the joint and can reduce the ability of the joint to function normally. Corticosteroids are a group of medications with anti-inflammatory properties. Corticosteroids may reduce the consequences of inflammation in the joints. For children with septic arthritis who are taking antibiotics compared to placebo (fake medication) 1. Corticosteroids may reduce pain in affected joints at one year of follow-up 2. Corticosteroids may improve normal function of affected joints at one year of follow-up 3. Corticosteroids may reduce days of intravenous antibiotic treatment needed 4. Corticosteroids may have little or no effect on total or serious adverse effects We do not have information about the effects of corticosteroids on activities of daily living. What happens to children with septic arthritis who take corticosteroids in addition to antibiotics? Absence of pain 1. 24 more of 100 children experienced absence of pain after 12 months with corticosteroids (24% absolute improvement) 2. 96 of 100 children experienced absence of pain compared to 72 of 100 children who took a placebo Activities of daily living Included studies did not report this outcome. Normal physical joint function 1. 24 more of 100 children who received corticosteroids had normal function of the joint after 12 months (24% absolute improvement) 2. 98 of 100 children experienced absence of pain compared to 74 of 100 children who received a placebo Number of days of intravenous antibiotic treatment 1. Children who received corticosteroids compared with placebo had 2.77 fewer days of intravenous antibiotic treatment 2. Children who received corticosteroids had 8.09 days of intravenous antibiotic treatment 3. Children who received placebo had 10.86 days of intravenous antibiotic treatment Length of hospital stay 1. We are uncertain whether corticosteroids had an effect on the length of hospital stay because the evidence was of very low quality Total or serious adverse events 1. None of the patients treated with corticosteroids reported adverse effects at 12 months Quality of the evidence Overall, these studies provided low-quality evidence due to small numbers of study participants and concerns about study design. Evidence on length of hospital stay was of very low quality, as this was not clearly reported.
This review systematically examines the evidence supporting this practice. From the evidence available, we were unable to draw any firm conclusion about using these medicines to treat aggression. Four antiepileptic drugs (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) helped to reduce aggression in at least one study. However, for three of these drugs (valproate, carbamazepine and phenytoin) we found at least one other study where there was no significant improvement. Further research is needed to clarify which antiepileptic drugs are effective for whom. Such research is best carried out using carefully designed clinical trials. Such trials need to take account of the type of aggression displayed, the severity of the aggression, and any other disorders experienced by the participants.
In this review, the authors looked for studies that compared death rates in patients with an abdominal injury where ultrasound was used to aid diagnosis with death rates where no ultrasound was used. They also looked for evidence that ultrasound use could reduce the need to carry out other more complex and more expensive diagnostic tests. However, very few trials have been done and the authors concluded that there is insufficient evidence to justify the use of ultrasound as part of the diagnosis of patients with abdominal injury. Given this degree of uncertainty, it is probably justified to ask doctors on duty for a confirmatory CT scan in patients who have sustained an injury with a high chance of major trauma (that is, head and brain injury, cervical spine fracture, thoraco-abdominal pelvic trauma, and other injuries).
This review of 20 studies involving 1898 subjects found laser techniques to be useful and relatively safe alternatives to TURP. The small number of enrolled subjects and differences in study design limit any definitive conclusions regarding which type of laser technique is the most effective. Improvements in LUTS and urine flow slightly favored TURP, though laser procedures had fewer side effects and shorter hospitalization times. The follow-up durations of these studies ranged from 6 to 36 months and men with extremely large prostates were generally excluded from the trials. The risk of needing a reoperation for recurrent LUTS was higher following laser procedures. Study results were insufficient to adequately compare laser techniques with other minimally invasive procedures. More studies, using randomized treatment assignment, enrolling larger numbers of subjects, and comprehensive measures of treatment effectiveness and side events, are needed to better define the long-term safety and durability of laser techniques for treating LUTS associated BPO.
Our search identified one trial involving 425 women and their babies. In this trial, 214 women had an induction of their labour at term, the other 211 women waited for a spontaneous onset of their labour. The findings of this trial highlighted no clear difference between the babies of women in either group in relation to the number of large babies, baby's shoulder getting stuck during birth or babies with breathing problems, low blood sugar and admission to a neonatal intensive care unit. No baby in the trial experienced birth trauma. In the group of women whose labour was induced, there were more incidences of jaundice in the babies. There was no clear difference between women in either group in relation to serious health problems for women, caesarean section, instrumental vaginal birth, postpartum haemorrhage, admission to an intensive care unit and intact perineum. There were no reports in either group of maternal deaths. It should be noted that most of the evidence was found to be of very low quality. The following outcomes were not reported: postnatal depression, maternal satisfaction, length of postnatal stay (mother), babies with high blood acid, bleeding in the baby's brain, other brain problems for the babies, babies small-for-gestational age and length of baby's postnatal stay. There is insufficient evidence to clearly identify if there are differences in health outcomes for women with gestational diabetes and their babies when elective birth is undertaken compared to waiting for labour to start spontaneously or until 41 weeks' gestation if all is well. More research is needed to answer this question.
We found 19 randomised trials that together included 2286 participants. The dose of oxygen per treatment session in the HBO arm was remarkably uniform, with all trials except one administering external beam radiation therapy at 3 atmospheres absolute (ATA). However, the number of treatments given ranged widely, from two sessions only, separated by three weeks, up to 40 sessions over eight weeks.The total dose of radiation was generally reduced in the HBO participants in order to reduce side effects. The follow-up period varied between trials, from six months to 10 years, although most studies followed participants for between two and five years. Adding HBO to the treatment of head and neck cancers reduced mortality at both one year and five years after therapy. Local tumour recurrence was also less likely with HBO at one year and five years in head and neck cancer. However, these advantages are achieved at the cost of some adverse effects. There was a significant increase in the rate of severe radiation tissue injury and the chance of seizures during HBO therapy. The quality of evidence was generally high with close agreement between several different trials. Similarly, there was high-quality evidence of an increased risk of having a severe reaction to the radiation while breathing HBO. The evidence for an increased risk of seizures during treatment when using HBO was of moderate quality, mainly because of the small numbers of seizures seen in the included studies. There is some evidence that breathing oxygen while at raised pressure may improve mortality and reduce tumour regrowth in cancers of the head and neck, but at the cost of increased side effects.
For this review, we searched for additional trials on the effect of music interventions on stress and anxiety in people with coronary heart disease. We searched for studies published up until November 2012 as well as ongoing studies until November 2012. We considered all studies in which any form of participation in music (e.g. listening to music, singing, playing music) was compared with any form of standard treatment and included persons with confirmed coronary heart disease. We identified four new trials for this update. This review includes 26 trials with a total of 1369 participants. The trials were small in size. The findings suggest that listening to music may have a beneficial effect on systolic blood pressure and heart rate in people with coronary heart disease. Listening to music also appears to be effective in reducing anxiety in people with myocardial infarction, especially when they are given a choice of which music to listen to. Listening to music may also reduce pain and respiratory rate. However the size of the effects on pain and respiratory rate is small. Therefore, its clinical importance is unclear. Finally, listening to music appears to improve patients' quality of sleep following a cardiac procedure or surgery. We found no evidence of effect for depression or heart rate variability, and inconsistent results for mood. No adverse effects of music interventions were reported. The majority of the studies examined the effects of listening to pre-recorded music. More research is needed on the effects of music interventions offered by a trained music therapist. Overall, the quality of the evidence is not strong thus the results should be interpreted with caution. We did not identify any conflicts of interests in the included studies.
We found five randomised trials, which together included 336 participants; half received pentoxifylline, and the other half received placebo or no intervention. We performed this systematic review and statistical analyses but could not show firm evidence of beneficial effects of pentoxifylline on mortality or on complications of liver diseases in patients with alcoholic hepatitis. Pentoxifylline did appear to cause more serious and non-serious side effects. In order to help decide whether pentoxifylline should be used to treat alcoholic hepatitis or not, we need well-designed, well-conducted, large randomised clinical trials, with short-term (less than one month) and long-term (more than one month) data on benefits and harms.
Non-epileptic attacks look like epileptic seizures but they are not caused by epilepsy. There have been many investigations of the causes, but evidence about successful treatment is less available. We reviewed the existing studies treating people having non-epileptic attacks. We found 12 studies looking at different types of treatment such as psychotherapy, cognitive behavioural therapy and hypnosis. Three hundred and forty three participants were recruited to these 12 studies. Four studies were randomised controlled trials, and 8 were non-randomised studies. Most of the controlled trials included patients with other diagnoses as well as non-epileptic attacks. Most of the non-randomised studies included patients with mainly non-epileptic attacks. Most included studies reported improved outcomes for the treatment they were investigating. One randomised trial investigating Cognitive Behavioural Therapy found that seizures were significantly reduced. Due to the variety of treatments and designs of the included studies, it was not possible to combine the results to produce an overall outcome for our review. Many of the studies did not use satisfactory methods which meant that the evidence was rated as high risk of bias. The overall evidence for the main outcome of reducing seizures as a result of treatment is not considered reliable except in one study. Our conclusion is there is little reliable evidence to support the use of any treatment for people with non-epileptic attacks. The evidence in this review is up to date as from 4 February 2013.
We searched for studies up to March 2013. We found 16 studies, including two high quality randomised controlled trials and 14 studies collecting data from HIV care programmes. All but one study was conducted in Africa. The study participants included both adults and children who were followed-up for up to two years. We describe three types of care: - Partial decentralisation: starting antiretroviral therapy at the hospital, then moving to a health centre to continue treatment - Full decentralisation: starting and continuing treatment at a health centre - Providing antiretroviral therapy in the community: antiretroviral therapy is started at a health centre or hospital and thereafter provided in the community We found that if antiretroviral therapy was started at a hospital and continued in a health centre (partial decentralisation), there was probably less attrition and fewer patients were lost to care after one year (four studies, 39 090 patients). Where antiretroviral therapy was started and continued at a health centre (full decentralisation), there was probably no difference in the number of deaths and patients lost to follow-up (attrition), but overall, there were probably fewer patients lost to care after one year (four studies, 56 360 patients). If antiretroviral therapy was provided in the community, by trained volunteers, there was probably no difference detected in death or losses to care when compared to care provided at a health centre after one year (two studies, 1 453 patients). Overall, none of the models of decentralisation led to worse health outcomes. The research indicates that fewer patients are lost to care when they are continued on antiretroviral therapy at health centres rather than in hospitals. The research also did not detect a difference in the numbers of patients lost to care when they are treated in the community rather than in a health facility.
We searched for trials up to June 2014 and included 21 randomised controlled trials, involving 1746 participants, of mailuoning for people with acute ischaemic stroke. Two trials followed up participants for three months after treatment ended, but the duration of the other trials was shorter, from 14 to 38 days. A government agency funded one of the 21 included trials. We assessed 20 trials to be of a low quality. When we analysed these trials together, there was no significant difference for adverse events between the mailuoning-treatment group and the control group; mailuoning improved neurological impairment and cognitive function significantly. One trial, assessed to be of a higher quality, failed to show any significant improvement made by mailuoning on neurological deficit, activities of daily life, or quality of life. There was no convincing evidence from trials with sufficient methodological quality to support the routine use of mailuoning to promote recovery after stroke. High-quality large-scale randomised controlled trials are needed to confirm its effect. We assessed 20 of the 21 included trials to be of a poor quality for their study design; we assessed one trial to be of a higher quality, but there were fewer participants in this trial. Overall, the quality of evidence was poor.
The review found 34 trials including more than 19,000 women of whom over 9000 received oestrogen. The review found that significantly more women who received local (vaginal) oestrogen for incontinence reported that their symptoms improved compared to placebo. There was no evidence about whether the benefits of local oestrogen continue after stopping treatment but this seems unlikely as women would revert to having naturally low oestrogen levels. Trials investigating systemic (oral) administration, on the other hand, found that women reported worsening of their urinary symptoms. The evidence comes mainly from two very large trials including 17,642 incontinent women. These trials were investigating other effects of hormone replacement therapy as well as incontinence, such as prevention of heart attacks in women with coronary heart disease, bone fractures, breast and colorectal cancer. In addition, in one large trial women who did not have incontinence at first were more likely to develop incontinence. There may be risks from long-term use of systemic oestrogen, such as heart disease, stroke and cancer of the breast and uterus.
The review identified one trial, involving 147 women. This trial was conducted to explore the benefit of routine prophylactic antibiotics (intervention group) versus placebo (control group) for women with severe perineal tears. The result showed fewer perineal wound complications in the intervention group at two weeks postpartum. There was no statistically significant difference in perineal wound complications before discharge and at six weeks' postpartum. The one included study was terminated before it reached the pre-planned sample size and had a high rate of loss to follow-up The included study was of high methodological quality except for incomplete follow-up. We assessed reduction of perineal wound infection in third- or fourth-degree tear by antibiotic prophylaxis as low to moderate quality of the evidence. However, the results are based on one small trial and there was a high loss to follow-up. More research is needed.
We searched Cochrane Central Register of Controlled Trials, MEDLINE, online registries of ongoing trials, and conference proceedings. The evidence is current to September 2017. We found six trials eligible for inclusion, of which two are still ongoing, and one awaiting classification study. We included 268 adult and elder participants (no children were included). Two studies compared eltrombopag with placebo for patients with normal platelet counts before chemotherapy (to prevent CIT). One study compared romiplostim with placebo for patients with low platelet counts during chemotherapy (to prevent recurrence of CIT). All of the studies were funded by the drug manufacturers. To prevent CIT, the review shows that when patients (206 participants) with normal platelet count before chemotherapy are given eltrombopag (multiple-dose oral administration with chemotherapy), compared to placebo: - the use of TPO-RAs may make little or no difference to the all-cause mortality (low quality of evidence); - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (very low quality of evidence); - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (very low quality of evidence); - no studies were found that looked at overall survival, the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. To prevent recurrence of CIT, the review shows that when patients (62 participants) with low platelet counts during a chemotherapy cycle are given romiplostim (single-dose subcutaneous administration with chemotherapy), compared to placebo: - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one bleeding episode of any severity (very low quality of evidence); - there is not enough evidence to determine whether TPO-RAs reduce the number of patients with at least one severe/life-threatening bleeding episode (very low quality of evidence); - no studies were found that looked at overall survival, the number of treatment cycles with at least one bleeding episode, the number of days on which bleeding occurred, the amount of bleeding, or quality of life. We found one ongoing study (expected recruitment 74 participants), planning to give romiplostim (subcutaneous administration with chemotherapy) to participants. As yet, there are no reported outcomes. To treat CIT, one ongoing study (expected recruitment 83 participants) planned to give eltrombopag (seven days orally) to participants when their platelet counts are less than 75×109/L during chemotherapy. Its completion date (March 2017) has passed and no results have been reported. One study awaiting classification included patients with normal platelet counts before chemotherapy (to prevent CIT), patients with low platelet counts during chemotherapy (to prevent recurrence of CIT), and others (uncertain whether CIT had happened). There was no evidence for a difference in the number and severity of bleeding episodes. This study did not address overall survival or quality of life. There is low and very low quality evidence for the use of TPO-RAs to prevent CIT or prevent recurrence of CIT in patients with solid tumours. No certain conclusions can be drawn due to the lack of strong evidence in the review. The available weak evidence did not support the use of TPO-RAs for preventing CIT or preventing recurrence of CIT in patients with solid tumours. No completed studies looked at the use of TPO-RAs for treating CIT in patients with solid tumours.
The review identified four randomised controlled studies involving 3956 women and 3893 babies, which compared corticosteroids with usual care or placebo. Giving the mother intramuscular antenatal corticosteroids may reduce the chances of a baby needing special care for respiratory problems, and may reduce the chances of the baby being admitted to a neonatal intensive care unit. Much larger numbers of women would be needed to confirm differences in the rates of the respiratory problems themselves and any possible harms of giving the corticosteroids, for the mother and the baby. The quality of evidence from the included randomised trials was low. This means that we can not be completely confident that future trials will come to the same conclusions about the treatment benefits for the babies of mothers receiving a course of antenatal corticosteroids prior to caesarean section. Evidence suggest that there might be a beneficial effect of intramuscular corticosteroids in respiratory outcomes of the neonate in the immediate period after birth. Given that only one study has examined the long-term effects, we cannot be certain about whether there are risks and what is their magnitude. Larger randomised trials should be conducted in order to confirm the short- and long-term effects of this intervention in the general population of women undergoing elective caesarean section.
This review of 16 trials in 34,369 non-surgical patients who suffered an acute medical illness found that heparin reduced the number of patients suffering DVTs but also increased the risk of bleeding complications when compared to participants that received a placebo or no medication. We had some concerns over how reliable the results were from the unblinded studies, which made up just under half of the studies. Also, most of the studies were lacking explanations of how the allocation of the treatments was performed. The lower risk of PEs (when combining those that caused death and those that did not) with heparin could have been a chance effect. There was no clear evidence of a difference in the rate of death or thrombocytopaenia. The review also found that patients who were given LMWH developed fewer DVTs and fewer bleeding complications compared with those given UFH, leading to the conclusion that LMWH is more effective and carries a lower risk of adverse events in preventing blood clots than with UFH. There was no clear evidence of differences between LMWH and UFH for PE, death or thrombocytopaenia.
We found three studies that recruited a total of 59 cancer patients (37 men and 22 women) aged between 54 and 78 years. Forty-seven cancer patients completed the treatment. Studies differed in study design and included people with a variety of cancers. Studies also differed in dosage, route of injection, frequency and duration of treatment. One study compared ghrelin with a placebo while two studies compared different doses of ghrelin (higher dose with lower dose). Outcomes of interest to cancer patients with loss of appetite and weight loss, such as improvement in food intake and improvement in body weight, were not adequately reported. All three included studies were funded by government agencies. One study received an additional grant from a pharmaceutical company. We found insufficient evidence that using ghrelin demonstrated differences in food intake. We found no evidence that using ghrelin alone or in combination made any difference to body weight. We could not reach any conclusions about its side effects. The limited amount of information means that we could not draw any conclusions. We rated the quality of evidence from studies using four levels: high, moderate, low, or very low. High-quality evidence means that we are very confident in the results. Very low-quality evidence means that we are very uncertain about the results. The evidence in this review was of very low quality.
The evidence is current up to 22 February 2019. There were eight studies conducted including 500 people in hospital. There were seven different ways in which nutrition was given. 1. Feeding into a vein versus oral nutrition: based on one study that included 157 people, we found that feeding into a vein may increase complications after surgery. However, there may be little or no difference in length of hospital stay. 2. Immuno‐enhancing nutrition versus standard supplements: immuno‐enhancing nutrition has high levels of nutrients that are thought to improve the immune function and was given in one study that included 29 people. We found that this form of nutrition may decrease complications 90 days after surgery, but may have little effect on length of hospital stay. 3. Preoperative oral nutrition support versus diet: based on one study that included 28 people, we are uncertain if oral supplements before surgery improve complications after surgery. Length of hospital stay was not reported. 4. Early postoperative feeding versus standard care: based on one study that included 102 people, early postoperative feeding may increase postoperative complications after surgery, but we are very uncertain of this finding. Length of hospital stay may be similar. 5. Amino acids versus dextrose: amino acids are the building blocks of proteins and dextrose is sugary water. From two studies that included 104 people, we are uncertain whether complications may be reduced. Length of hospital stay may be similar. 6. Branch chain versus dextrose: branch chain are a type of amino acid. From one study that included 19 people, we are very uncertain whether complication rates are similar. Length of hospital stay was not reported. 7. Perioperative oral nutritional supplements versus multivitamin and mineral supplement: from one study that included 61 people, oral supplements compared to a multivitamin and mineral supplement may slightly decrease postoperative complications. Length of hospital stay may be similar. The certainty of the evidence for all outcomes in this review was low or very low, meaning that the true effect may be very different or is likely very different from what we found.
The review authors searched scientific databases and Internet resources to identify randomised controlled trials (where participants are allocated at random to one of two or more treatment groups) of interventions to reduce, eliminate, or prevent relapse of drug use or criminal activity of drug-using offenders. We included males and female of any age or ethnicity. We identified 14 trials of pharmacological interventions for drug-using offenders. The interventions included: (1) naltrexone in comparison with routine parole, social psychological treatment or both; (2) methadone maintenance in comparison with different counselling options; and (3) naltrexone, diamorphine and buprenorphine in comparison with a non-pharmacological alternative and in combination with another pharmacological treatment. Studies could not be combined all together because the comparisons were too different. When compared to non-pharmacological, we found low quality evidence that agonist treatments are not effective in reducing drug use or criminal activity . We found low quality of evidence that antagonist treatment was not effective in reducing drug use but we found moderate quality of evidence that they significantly reduced criminal activity. When comparing the drugs to one another we found no significant differences between the drug comparisons (methadone versus buprenorphine, diamorphine and naltrexone) on any of the outcome measures suggesting that one pharmacological drug does not preside over another. One study provided some cost comparisons between buprenorphine and methadone, but data were not sufficient to generate a cost-effectiveness analysis. In conclusion, we found that pharmacological interventions do reduce subsequent drug use and criminal activity (to a lesser extent). Additionally, we found individual differences and variation between the degree to which successful interventions were implemented and were able to sustain reduction of drug use and criminal activity. This review was limited by the lack of information reported in this group of trials and the quality of the evidence was low. The evidence is current to May 2014.
The reviewers found 17 studies of programs that reported whether working with problem drinkers reduced injuries. Several different approaches were evaluated, the most common being brief counseling by health workers. The evidence from these studies suggests that action with problem drinkers is effective in reducing both injuries and events that lead to injury (such as falls, motor vehicle crashes, and suicide attempts). However, more research is needed to calculate the level of effectiveness accurately and to determine which type of program works best.
Ten studies examined the effects of working wrist splints, resting hand and wrist splints, and wearing special shoes/ insoles in people with rheumatoid arthritis. Although there is no evidence that wearing resting wrist and hand splints changed pain, grip strength, or number of swollen joints, participants who wore these splints for two months preferred to wear them, and also preferred padded splints. One study provided evidence that wearing extra-depth shoes for two months resulted in significant benefits of less pain on walking and stair climbing. Extra-depth shoes with semi-rigid insoles provided better pain relief than extra-depth shoes alone.
This review included data from 31 clinical trials involving 8019 participants. In the short-term (less than six weeks) treatment of eczema, we found pimecrolimus was more effective and well-tolerated when compared against vehicle (cream base not containing any pimecrolimus). Likewise, pimecrolimus was better than vehicle cream in preventing deterioration in eczema based on data from 9 trials involving 3091 participants. However, we found that 3 weeks treatment with pimecrolimus was less effective than a moderate (triamcinolone acetonide, data from 1 trial with 658 participants) and a potent topical corticosteroid (betamethasone valerate, data from 1 trial with 87 participants). Furthermore, 6-weeks treatment with pimecrolimus was less effective and caused more participants to drop out of treatment due to lack of efficacy than tacrolimus based on 2 trials involving 639 participants. Pimecrolimus caused a similar rate of adverse events to vehicle cream but had a lower overall dropout rate. In contrast, pimecrolimus had higher dropout rates and caused more skin burning than topical corticosteroids. None of the trials reported on key adverse effects, such as thinning of skin. Pimecrolimus caused a similar rate of adverse events to tacrolimus. There were no cancer-related events reported in any of the 31 clinical trials. This review did not find evidence to support the notion that pimecrolimus was better than moderate or potent corticosteroids or tacrolimus in treating eczema. However, there is a distinct lack of trials comparing pimecrolimus against mild-potency corticosteroids.
The evidence is current to February 2013. We included 28 studies that randomised 6871 women. Women were assigned to receive either a taxane-containing chemotherapy regimen (single taxane or in combination with other chemotherapy drugs) or a non-taxane chemotherapy regimen. There were variations in the taxane-containing chemotherapy regimen and the non-taxane treatments. Approximately half of the studies used paclitaxel and the other half used docetaxel, and in the majority of cases, taxanes were administered every three weeks. Of the 28 studies, 20 studies included women who received taxanes as their first treatment after their diagnosis of metastatic breast cancer, and 21 studies involved women who had not been previously treated with anthracyclines in the metastatic setting. From those studies reporting median follow-up, this ranged from 9 months to 69 months. This review showed that chemotherapy regimens including taxanes improved survival and decreased the progression of metastatic breast cancer. If the analyses were restricted to those studies where women received taxanes as their first treatment after their diagnosis of metastatic breast cancer, the survival benefit persisted. Taxanes also appeared to cause tumours to shrink more than chemotherapy regimens without taxanes. However, there were differences in side effects. The risk of experiencing neurotoxicity (tingling of hands and feet) with taxanes increased compared to non-taxane chemotherapy. Hair loss also seemed to be more likely with taxane than with non-taxane-containing regimens. However, less nausea/vomiting was observed with taxanes. There was no difference in the rates of leukopaenia (low white blood cells) or treatment-related deaths between taxane and non-taxane chemotherapy. Of the studies that reported quality of life measures, there did not appear to be any differences (overall or on subscales) in quality of life between the two groups. We considered 19 out of the 28 studies to be at low risk of bias overall. However, some studies failed to report details on concealing drug treatments and methods of outcome assessment for those outcomes more likely to be at risk of bias (for example tumour response rate). The degree of variability seen across the included studies probably reflects the varying efficacy of the non-taxane chemotherapy regimens used in these studies and indicates that taxane-containing chemotherapies are more effective than some, but not all, non-taxane-containing regimens.
We included 32 studies; 21 randomised controlled trials (in which children were randomly assigned to receive either supplementary feeding (intervention group) or not (a control group), and 11 controlled before-and-after studies (in which outcomes were observed before and after treatment in a group of children who were not randomly assigned to an intervention and a control group). The number of children in them ranged from 30 to 3166. Most studies were from low- and middle-income countries; three were from high-income countries. We found that, in low- and middle-income countries, providing additional food to children aged three months to five years led to small gains in weight (0.24 kg a year in both RCTs and CBAs) and height (0.54 cm a year in RCTs only; no evidence of an effect in other study designs),and moderate increases in haemoglobin. We also found positive impacts on psychomotor development (skills that involve mental and muscular activity). We found mixed evidence on effects of supplementary feeding on mental development. In high-income countries, two studies found no benefits for growth. The one effective study involved Aboriginal children. We found that food was often redistributed ('leakage') within the family; when feeding was home-delivered, children benefited from only 36% of the energy given in the supplement. However, when the supplementary food was given in day care centres or feeding centres, there was much less leakage; children took in 85% of the energy provided in the supplement. When we looked at different groups supplementary food was more effective for younger children (under two years old) and for those who were poorer or less well-nourished. Results for sex were mixed. Feeding programmes that were well-supervised and those that provided a greater proportion of required daily food for energy were generally more effective. We judged evidence from the RCTs to be of moderate quality and evidence from the CBAs to be of low quality.
We included 32 trials (2281 participants), published up to November 2019. Twelve trials compared shock wave therapy to placebo. Eleven trials compared high- and low-dose shock wave therapy, although dosages varied across trials. Single trials compared shock wave therapy to other treatments including ultrasound-guided glucocorticoid needling, transcutaneous electric nerve stimulation (TENS), exercise, or no treatment; or different regimens of shock wave therapy. Overall, 61% of participants were women, the average age was 52 years, and the average duration of the condition was 33 months. Two trials were funded by manufacturers of shock wave machines. Participant-reported pain relief of 50% or greater (one trial): • four more people out of 100 reported pain relief of 50% or more (ranging from 19 fewer to 26 more). 42 out of 100 people reported pain relief of 50% or greater with shock wave therapy compared with 38 out of 100 with placebo. Pain (higher scores mean more pain) (nine trials): • Improved pain by 8% (ranging from 2% better to 14% better) or 0.78 points better (ranging from 0.17 better to 1.4 better) on a 0- to 10-point scale. People who had shock wave therapy rated their pain as 2.2 points and people who had placebo rated their pain as 3 points. Function (ability to use the shoulder; higher scores meanbetter function) (nine trials): • Improved by 8% (ranging from 1.6% to 14%) or 8 points better (ranging from 1.6 better to 14 better) on a 0- to 100-point scale. People who had shock wave therapy rated their function as 74 points and people who had placebo rated their function as 66 points. Participant-reported success (six trials): • 15% (ranging from 3% fewer to 49% more) more people reported their treatment a success. 41 out of 100 people reported treatment success with shock wave therapy and 26 out of 100 people reported treatment success with placebo. Withdrawals due to side effects (seven trials): • 3% fewer (ranging from 6% fewer to 3% more) people withdrew from treatment due to side effects. 8 out of 100 people withdrew from treatment with shock wave therapy and 10 out of 100 people withdrew from the placebo group. Side effects (five trials): • 19% more people reported side effects (ranging from 7% more to 40% more): 26 out of 100 people had a side effect with shock wave therapy and seven out of 100 people had a side effect with placebo. In people with rotator cuff disease, moderate-certainty evidence (downgraded due to bias) shows that shock wave therapy probably does not improve pain and function compared with placebo, and low-certainty evidence (downgraded due to bias and lack of accuracy) shows there may be no improvement in those with a pain reduction of 50% or more and participant-reported success. We are uncertain if withdrawals or side effects differed between groups due to small number of events. It did not appear to matter if participants had calcific deposits or not. We are uncertain if higher doses of shock wave therapy have benefits with more side effects compared with lower doses, as there was only low- or very low-certainty evidence available, and we cannot recommend a particular treatment dose. Side effects included treatment-related pain, bruising and bleeding although these were generally minor and short-lived. Rare and serious side effects, including loss of blood supply and bone death, while possible, were not reported.
The review includes one study with 39 people with mucopolysaccharidosis type VI aged between five and 20 years old. The study compared galsulfase to placebo (a substance which contains no medication) and people were selected for one treatment or the other randomly. The study lasted for 24 weeks (with an open-label extension period of an additional 24 weeks). Given that there is only one small study included, the evidence for this treatment is limited. The included study showed that motor function improved in people who had received galsulfase, especially in their ability to walk. There was also an improvement in the results of urine tests, which showed lower levels of the chemicals associated with MPS VI (glycosaminoglycan levels). These results were seen in a short study and may reflect only short-term effects. There were no significant differences between treatment with galsulfase and placebo in relation to adverse effects. More research is required to study the long-term effects on heart and lung function, quality of life and survival. The methods of the study design were not clearly described and the impact of this on possible bias is unclear.
Five retrospective studies (including 535 women with a diagnosis of GCT) met our inclusion criteria. Two studies, which attempted to identify factors associated with better outcomes (in terms of overall survival), suggested that no apparent evidence could be found of differences in overall survival between surgical approaches (including whether the surgery was keyhole or open) whether a patient underwent lymphadenectomy (removal of lymph nodes) or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all women combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent only surgery. In three studies, no apparent evidence to suggest that disease recurrence was associated with type of adjuvant chemotherapy or type of surgery, although surgical staging may be important. In one study, disease recurrence was not noted to be different between patients who underwent fertility-sparing surgery, where only the affected fallopian tube and ovary were removed, and those treated with conventional surgery, in which both tubes and ovaries were removed. Given the high overall survival rate, fertility-sparing surgery may be an important treatment option for young patients wishing to have children in the future. Recurrence-free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life. All studies were at very high risk of bias (low quality). All five studies were retrospective (looked at past findings) and were at very high risk of bias (low quality); therefore future studies should look at current evidence in randomised studies on adult GCT of the ovary. Three randomised studies comparing chemotherapy are ongoing. The study that may be able to answer the question regarding best choice of chemotherapy in sex cord stromal tumours is an ongoing randomised study comparing the efficacy of two drugs (carboplatin and paclitaxel) versus standard chemotherapy (BEP - bleomycin, etoposide, cisplatin). Overall, the evidence in this review is of low quality, which may seriously weaken confidence in the results. Further research is very likely to have an important impact on evidence provided in the future. The effectiveness and safety of different ways of treating patients with adult-onset granulosa cell tumour of the ovary have not yet been assessed by high-quality studies. Such trials are required to assess toxicity and quality of life associated with different treatments and to assess the safety of the types of surgery used. Generally, current evidence is not robust enough to allow recommendations for changes in clinical practice.
This review examined seven randomised trials which included 296 participants. Although overall all the trials were classed as being at low or unclear risk of bias, the sample size of the included trials was small and there was unclear reporting of outcomes. Two different calcium channel blockers were included: nifedipine and nicardipine. Comparisons in six trials were with placebo and in one trial with both placebo and another type of drug (although only data relating to the calcium channel blocker and placebo were used in this case). Treatment with oral calcium channel blockers was found to be minimally effective in primary Raynaud's phenomenon, reducing the frequency of attacks by around 1.7 attacks per person per week. One trial provided information on duration of attacks reporting no difference between the calcium channel blocker and placebo groups . Oral calcium channel blockers had no effect on severity scores in the two trials in which these were assessed. Only two trials reported preference scores (whereby participants are asked which treatment they prefer) specifically in those with primary Raynaud's phenomenon, and in only one of these was there a between-treatment group difference (participants preferred nifedipine to placebo). Physiological measurements (for example measurement of finger blood flow) were performed in five trials, data could not be combined as the methods were too different, no differences found between calcium channel blocker and placebo treatment were seen in any trial. Treatment with calcium channel blockers was associated with a number of adverse events including headaches, flushing and ankle swelling. Quality of the evidence The results of this review were limited by the low number of participants recruited to the studies and by the limitations of currently used outcome measures. This review shows moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon, as measured by the frequency of attacks, and high quality evidence that they have little effect on severity. We are unable to comment on duration of attacks and patient preference due to the very low and low quality of evidence provided by the trials in relation to these outcomes.
We found six studies, with a total of 334 adult participants. We found no studies that included people younger than 18 years of age. Four studies investigated psychological interventions. One study investigated an exercise intervention, and another investigated repetitive transcranial magnetic stimulation (rTMS). Three studies compared a psychological therapy (cognitive behaviour therapy or mindfulness-based cognitive therapy) with a no-treatment control intervention. When the data for these studies were combined, there was no reliable effect in support of psychological therapy. One study compared cognitive behavioural therapy with another psychological intervention (supportive psychotherapy), and did not find an effect in favour of either intervention. One study compared a supervised exercise programme with exercise as usual, but did not find a effect in favour of either intervention. One study compared rTMS plus an antidepressant medication with the antidepressant medication alone. Because the quality of the evidence was very low, it was not possible to draw the conclusion that the addition of rTMS improved outcomes. Only one study, of rTMS, reported any harmful effects and these were relatively minor and resolved quickly. The quality of the evidence was rated very low. All studies were at high risk of bias in some ways, and therefore it was not possible to draw conclusions in support of any intervention. There was a high degree of variability in the main results, which meant we could have little confidence in the findings. Some studies had major methodological flaws. It is not possible to recommend any particular treatment based on the current evidence. The review authors have made some recommendations to improve the quality of the evidence in future studies.
Two trials were included this review. One trial (considered to be at a high risk of bias) evaluated the impact of Hib vaccination during pregnancy and the other trial (judged to be at a low risk of bias) evaluated the impact of viral influenza vaccination during pregnancy. In one small study (involving 213 women, mainly Hispanic and with low income, and 213 neonates, conducted in the US), women were given either Hib vaccination or a placebo control at between 34 to 36 weeks gestation. This trial did not report on any of this review's primary outcomes, including: mortality, respiratory tract infection or sepsis among the women or their babies. Nor did the study report on any of this review's other secondary outcomes apart from preterm birth and there were no clear differences between the vaccination and placebo groups. In one large trial (involving 2116 women and 2049 infants, conducted in Soweto, South Africa) pregnant women received either inactivated viral influenza vaccination or a placebo control. Viral influenza vaccination was associated with a reduction in confirmed influenza among women and their babies. However, there was no clear difference between groups in terms of pregnancy outcomes (miscarriage, preterm labour and stillbirth), influenza-like illness in women or their babies (high quality evidence), any respiratory illness, hospitalisation for respiratory infections and deaths among women (moderate quality evidence) and their babies (moderate quality evidence), neonatal hospitalisation for sepsis (moderate quality evidence), or maternal hospitalisation for any infection (moderate quality evidence). Similarly, there was no clear difference in any adverse systemic reactions between the vaccine and placebo groups. Evidence from one large high quality trial on the effectiveness of viral influenza vaccine during pregnancy suggests reduced reverse-transcriptase–polymerase-chain-reaction (RT-PCR) ) confirmed influenza among women and their babies, suggesting the potential of this strategy for scale up but further evidence from varying contexts is required. Further trials for both Hib and viral influenza vaccines with appropriate study designs and suitable comparison groups are required. There are currently two ongoing studies - these will be incorporated into this review in future updates.
A systematic overview of randomised trials does not provide sufficient evidence to determine whether thyroid hormone treatment of preterm infants with transiently low thyroid hormone levels results in changes in neonatal outcomes or reductions in developmental impairments. Extremely premature infants frequently have transiently low thyroid hormone levels in the first weeks after birth. These low thyroid hormone levels are associated with an increased incidence of complications and death in the newborn period and longer term developmental impairments. Thyroid hormone therapy might prevent these problems. One small trial comparing thyroid hormone treatment to no treatment of infants with transiently low thyroid hormone levels reported no benefit from treatment of these infants. However, this is insufficient evidence to determine if thyroid hormone treatment is effective. Further research is needed.
The aim of the review was to compare reduction or withdrawal of tacrolimus or cyclosporine without substitution with another immunosuppressive agent with continuation of tacrolimus or cyclosporine. Through systematic searches of medical databases we found one ongoing randomised clinical trial investigating total withdrawal of immunosuppressive drugs but, at the time of conducting this review, no trial results on the outcome measures of interest to this review were published. Thus, we cannot reach any conclusion on beneficial or harmful effects of calcineurin inhibitor minimisation for liver transplant recipient patients.
In this review article we have included 18 trials on the efficacy and safety of sugammadex. The trials included a total of 1321 patients. Sugammadex was shown to be more effective than placebo (no medication) or neostigmine in reversing muscle relaxation caused by neuromuscular blockade during surgery and is relatively safe. Serious complications occurred in less than 1% of the patients who received sugammadex. The results of this review article (specially the safety results) need to be confirmed by future trials on larger patient populations.
We identified 21 randomised controlled trials (clinical studies where people are allocated at random to one of two or more treatment groups) involving 909 participants treated with active medicines, and 846 who received placebo (a pretend treatment). Key features of dependent drug use are compulsive use, loss of control over use and withdrawal symptoms on cessation of drug use. This review included studies where participants were described as dependent or were likely to be dependent based on cannabis use occurring several days a week, or daily. The mean age of participants in individual studies ranged from 22 to 41 years, excluding three studies that targeted young people. Most (75%) study participants were male. Most (16) of the studies were undertaken in the USA, with three occurring in Australia, one in Canada and one in Israel. The studies tested a wide range of medicines to reduce the symptoms of cannabis withdrawal and to promote cessation or reduction of cannabis use. Four studies received study medicines from the manufacturing pharmaceutical company but none were funded by pharmaceutical companies. One study did not report funding or medicine source. For the outcome of abstinence at the end of treatment, Δ9-tetrahydrocannabinol (THC, the major constituent in cannabis) preparations were probably ineffective; antidepressants called selective serotonin reuptake inhibitors, mixed action antidepressants, a medicine called buspirone and a medicine called N-acetylcysteine may also have been ineffective; and we are uncertain about the effect of anticonvulsants and mood stabilisers. For the outcome of completion of the scheduled period of treatment, THC preparations, mixed action antidepressants, anticonvulsants and mood stabilisers may not have been effective, we were uncertain about the effect of SSRI antidepressants, and N-acetylcysteine probably did not support treatment completion. The use of anticonvulsants and mood stabilisers may have increased the likelihood that people left treatment early. THC preparations and N-acetylcysteine were probably no more likely to cause side effects than placebo, mixed action antidepressants and buspirone may have been no more likely to cause side effects than placebo, and we were uncertain about SSRI antidepressants. Based on current research, all medicines should be considered still experimental. The quality of the evidence for many of the outcomes in this review was low or very low because each medicine was investigated by a small number of studies (ranging from one to four), each study involved small numbers of participants, there was some inconsistency in the findings and there was a risk of bias due to study participants dropping out of treatment.
We found 11 studies up to November 2013, examining 1172 people, with studies ranging from 22 to 325 participants, and people aged from 12 to 70 years. All had tried non-surgical treatments and all had leg pain that was worse than their back pain. The follow-up period after surgery ranged from five days to 56 months. People who had a MD/OD had less pain in their legs, and less low back pain, but the difference was small. They were less likely to need a second operation because the first had been unsuccessful. They felt slightly better in some physical aspects of their quality of life, but again the difference was too small to be meaningful. In terms of complications, the two operations were similar, though people who had a MD/OD were more likely to have wound infections. Many of the studies were carried out on a small number of people and had a high risk of bias, so the overall quality of the evidence for leg and low back pain was low.
We included all studies that assessed fertility and early pregnancy outcomes in women who had local treatment of CIN versus untreated women. We identified fifteen suitable studies.Fertility outcomesThe results suggest that local treatment of the cervix does not adversely affect the ability to conceive; in fact the overall pregnancy rate was higher for treated women when compared to untreated women (43% versus 38%). There was no difference in the pregnancy rates in women that intended to conceive (88% treated versus 95% untreated) or in the number of women requiring more than 12 months to conceive (15% treated versus 9% untreated). Early pregnancy outcomes  The rates of total (less than 24 weeks of gestation) and first trimester (less than 12 weeks of gestation) miscarriage were no different. However, women after treatment had a significantly higher second trimester miscarriage rate (between 12 and 24 weeks of gestation) compared to untreated controls (1.6% versus 0.4%). The rates of ectopic pregnancies and terminations of pregnancy were higher for treated versus untreated women. The results should be interpreted with caution as the included studies were small and of mixed design. Most of the studies were of low quality and retrospective (looking at information recorded previously). Investigation of the effect of different treatments techniques and of the size of the tissue removed (i.e. cone length) was not possible. The results suggest that treatment for CIN does not adversely affect the chances of a successful conception, although treatment is associated with an increased risk of miscarriage in the second trimester. These conclusions should be interpreted with caution as the quality of the included studies was low or very low. Future research should investigate the impact related to the extent of the treatment and the treatment method used.
We reviewed the evidence in February 2018. We included 25 randomised controlled trials (a type of experiment in which participants are randomly assigned to one or more treatment groups) involving 10,996 women. We included studies examining the administration of intermittent iron supplements versus no intervention, a placebo (dummy pill) or the same supplements given on a daily basis. Most studies were implemented in school settings and were mainly funded by international organisations, universities, and ministries of health within the countries. Approximately one-third of the included studies did not provide a funding source. The findings show that women receiving intermittent supplementation with iron alone, or in combination with folic acid or other nutrients, were less likely to be anaemic than those women who received no iron supplements or a placebo. They also had higher concentrations of haemoglobin and ferritin (a protein that carries iron). Intermittent supplementation also reduced the risk of having iron deficiency. The findings indicate that intermittent supplementation was as effective as daily supplementation in reducing the prevalence of anaemia and increasing haemoglobin concentrations, with fewer side effects. It had no effect on raising ferritin concentrations. We found scarce evidence on the effect of intermittent supplementation compared to placebo or daily supplementation on iron deficiency anaemia, all-cause morbidity, disease outcomes, adherence, economic productivity, and work performance. Intermittent iron supplementation in menstruating women may be an effective intervention for reducing anaemia and improving haemoglobin concentrations compared to no treatment, placebo or daily supplementation. Intermittent supplementation may be associated with fewer side effects compared to daily supplementation. The findings were not affected by whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or given to populations with different degrees of anaemia at baseline (starting point for comparisons). The evidence base was of overall low quality.
The review of studies including 15 trials and 1422 children found that there were some encouraging results in short term studies when nedocromil was compared on its own with placebo, particularly with regard to lung function tests. However, these results were not confirmed in one large, longer term study of four to six years duration, which did not show significant difference in the primary outcome of symptom free days. This study was conducted in children who had mild asthma. There may be a role for nedocromil in the management of moderate asthma, but it should be assessed in relation to inhaled steroids, whose efficacy is well-established. This particularly important in symptomatic asthma.
This review aimed to determine if increased fluids and diuretics or both could hasten the passage of stones and improve symptoms. Neither our initial review nor this subsequent update identified sufficient evidence to enable conclusions to be determined about the safety and effectiveness of increasing fluids or diuretics or both to treat people with acute ureteric colic. More and larger randomised controlled studies are required.
After searching for relevant trials up to 18 April 2018, we identified four studies conducted between 1972 and 2000. Across the four studies, a range of insecticide delivery methods were used, including handheld, vehicle-mounted, and aircraft-mounted spraying equipment. A variety of different insecticides, doses, and spraying times were also used to suit the local environment and the behaviour of the targeted mosquito species. In three studies, the evidence was considered to be unsuitable for reliably assessing the impact of space spraying on the number of cases of malaria. The remaining study, which took place in a single state in India and covered a combined population of 18,460 people, reported the number of malaria cases in the years preceding and following the introduction of space spraying. The evidence suggested that space spraying led to a decrease in the number of cases of malaria, but as the trial was conducted over 30 years ago and within one state in India, we cannot be certain that these findings are applicable in other areas where malaria occurs. Reliable research in a variety of settings will help to establish whether and when this intervention may be worthwhile.
This review has collected information from randomised controlled trials comparing continuous to intermittent nebulised delivery methods in acute asthma attacks. Overall, differences were found between the two methods, with continuous nebulisers producing a modest reduction in admissions compared to intermittent beta-agonist therapy. This finding was especially pronounced in severe acute asthma. Continuous nebuliser therapy may be more effective than intermittent nebulisers for delivering beta-agonist drugs to relieve airway spasm in selected asthma populations.
We identified 17 clinical trials recruiting 2422 stroke patients (searching completed to January 2017). Patients who were recruited tended to have a moderate degree of disability (able to walk with assistance) and be sufficiently well to consider returning home. We categorised services as those based on a multidisciplinary ESD team (with different levels of co-ordination and delivery) and those with no multidisciplinary team co-ordination (no ESD team). The length of initial stay in hospital was reduced by approximately five days for the ESD group. At an average of six months after their stroke ESD patients were more likely to be living at home (an extra five patients living at home for every 100 receiving ESD services; moderate-quality evidence). They were also more likely to be independent in daily activities (an extra six patients independent for every 100 receiving ESD services; moderate-quality evidence). We identified no apparent hazards in terms of patient mood or quality of life, carer mood or quality of life, or the risk of readmission to hospital. The greatest reductions in disability seemed to be present in trials based around a co-ordinated ESD team. When compared with usual care, costs of ESD services ranged from a reduction to a modest increase. The quality of the evidence was downgraded to 'moderate' for the main outcomes of death, discharge home or disability. This was because it was impossible to hide the treating service from participants or healthcare workers. These conclusions were not dependent on trials judged to be lower quality because of poor design or missing data. More information was missing for some of the other outcome measures, which we have downgraded to low-quality evidence. Appropriately resourced ESD services with co-ordinated multidisciplinary team input can reduce disability and the length of time in hospital at least for a selected group of people with stroke. Results are unclear for services that are not based on a co-ordinated multidisciplinary team input. We did not identify any substantial harmful effects.
We looked for studies lasting over one week. We included fifteen studies in the review. These studies did not show any difference between chest physiotherapy and other therapies in terms of lung function. Studies of acute infections showed improved lung function irrespective of type of treatment. Longer-term studies showed smaller improvements or decline. In ten studies participants preferred techniques they administered on themselves. The review was limited by the lack of well-designed long-term trials. We did not find evidence that conventional chest physiotherapy techniques were any better than other treatments for lung function. We can not recommend any single treatment over another at this time.
We found five trials, with 105 people. They all studied the immediate effects of a single treatment with MI-E. The studies compared MI-E to other ways of helping people cough, or normal cough without help. One trial studied MI-E when added to other treatment. Based on three trials, MI-E may improve the outwards flow of air during coughing compared to a normal cough without help. MI-E was not clearly better than other methods of improving cough. None of the studies measured the outcomes that we thought were important for making decisions about the usefulness of MI-E. For example, the studies did not report on survival, length of hospital stay, quality of life, or serious side effects. One study reported extreme tiredness as a side effect of MI-E. There was often not enough information in the reports to tell whether the studies were well run; in some we found design problems that could have affected the results. The findings of this review do not give enough evidence on which to make decisions. We were unable to find any information from trials on important short- and long-term effects, including side effects of MI-E in NMDs. There is currently insufficient evidence for or against the use of MI-E to help people with NMDs clear mucus from their lungs. Further studies are needed to better understand the benefits and risks of MI-E in relation to other methods of cough assistance. The evidence in the review is up to date as of 7 October 2013.
This review included 21 trials involving over 21,000 women. Four trials did not contribute data to the analyses. The trials were generally of variable quality. There were just three studies on vitamin E supplementation alone, but none of these studies contributed data. All other studies included vitamin C, and additional supplements or drugs. The findings indicate that routine supplementation with vitamin E in combination with other supplements during pregnancy did not improve outcomes for babies or women. There was a reduction in the number of placentas coming away early (placental abruption) in women given vitamin E supplements in combination with other agents, which was rated as high-quality evidence. However, it is unclear whether this finding was due to vitamin E or the other agents used in the supplement. This should be explored in further research examining the mechanisms leading to placental abruption. The review found there may be harms associated with vitamin E supplements in pregnancy, as there was an increased risk of abdominal pain and term prelabour rupture of fetal membranes in women supplemented with vitamin E in combination with other supplements. There was no increase in preterm prelabour rupture of membranes in women supplemented with vitamin E and other agents. The large body of evidence does not support taking vitamin E supplements, alone or in combination, during pregnancy. This is because taking vitamin E in combination with other supplements during pregnancy does not help to prevent problems in pregnancy including stillbirth, baby death, preterm birth, pre-eclampsia or low birthweight babies. In fact, it may increase abdominal pain for women and also increase the number of women having early rupture of membranes at term.
This systematic review of four studies (total of 40 participants) found insufficient evidence of benefit for any of the three classes of medications included in this review. There is a considerable lack of evidence to address pharmacological interventions for anxiety disorders in patients with COPD. We recommend that new research be conducted to ascertain the best mode of treatment for anxiety within this population. This new research needs to be of good methodological design, investigate an adequate number of patients and have a meaningful length of follow-up.
We included 17 studies, with a total of 1025 participants. Sixteen studies including 953 people compared betahistine with placebo; the studies were at high to unclear risk of bias. All studies with analysable data lasted three months or less. One study, at high risk of bias, included 72 people with benign paroxysmal positional vertigo (BPPV) and compared betahistine with placebo; all patients also had particle repositioning manoeuvres. We judged the quality of evidence overall to be low. The studies varied considerably in terms of types of participants, their diagnoses, the dose of betahistine and the length of time the drug was taken for, the study methods and the way any improvement in vertigo symptoms was measured. When all studies are taken together, the proportion of patients reporting a reduction of their vertigo symptoms was significantly higher in the betahistine group than in the placebo group. However, there was significant variability in the results of the studies so this result should be treated with caution. The proportion of patients reporting side effects of the medication was similar in both groups: 16% in the betahistine groups and 15% in the placebo groups. Overall, 16% of patients of both groups withdrew from the studies. There was insufficient information about the effect of betahistine on objective tests of inner ear balance organ function. There was no information on the effect of betahistine on overall quality of life or falls. We judged the quality of evidence from the included studies to be low, meaning our estimates of the effects of betahistine could turn out to be inaccurate. The evidence is up to date to September 2015. Low quality evidence suggests that patients suffering from vertigo from different causes may have some benefit from betahistine in terms of reduction in vertigo symptoms. Betahistine is generally well tolerated. Future research into the management of vertigo symptoms needs to use more rigorous methodology and include outcomes that matter to patients and their families.
Through searches of databases and web sites, we found 22 randomised and non-randomised studies that evaluated the effects of parenting programmes on childhood injuries or home safety. Fifteen of these were home visiting programmes that provided a range of support services, as well as parent education or training. These programmes were usually provided to families who were disadvantaged, whose children were considered to be at risk of poor health, or who may benefit from extra support. We pooled the results from 10 randomised controlled trials, which included a total of 5074 children, and found that children from families who had completed the parenting programmes had sustained fewer injuries than those from families who had not attended the programmes. We pooled the results from three randomized controlled trials that measured home safety using the Home Observation for Measurement of the Environment (HOME) tool. The results from these three studies, which included a total of 368 children, showed no difference in HOME scores between families receiving parenting programmes and those not receiving these programmes. Overall, the quality of the studies was reasonable. We conclude that parenting programmes are effective in reducing unintentional injury in children and can improve home safety, particularly in families who may be considered 'at risk,' such as some teenage or single mothers. It would be worthwhile for health and social care providers to make parenting programmes available to families.
Three randomised controlled trials (RCTs) involving 779 participants measured disease progression on special clinical rating scales of disease severity in ALS. The review authors collected data about adverse events from the included trials. The combined results from the two included studies that used the rating scale (AALSRS) showed a small significant benefit in favour of rhIGF-I. Significant flaws in the trial designs make the statistically significant benefits in some outcomes of questionable relevance. There was an increased risk of injection site reactions with rhIGF-I. A third study using a different outcome measure showed no difference between treatment and placebo. Taken together, the available RCTs do not provide information supporting the hypothesis that rhIGF-I is an effective disease modifying treatment for ALS. All three included studies showed a high risk of bias. These issues very seriously detracted from the ability of this review to fulfil its objectives.
Eighteen randomised controlled trials were included in the review, involving a total of 10,049 participants (78% were men) from seven different countries. The trials compared lipid-lowering therapy with placebo or usual treatment for at least 90 days. They differed considerably in the inclusion criteria, outcomes measured, and type of lipid-lowering therapy used. Lipid-lowering therapies improved walking distance. The effect of lipid-lowering therapy on death from any cause in people with peripheral artery disease was inconclusive. Using drugs to lower blood lipids had a beneficial effect on the incidence of total cardiovascular events, due primarily to an overall reduction in coronary events (OR 0.8; 95% Confidence Interval 0.7 to 0.9). The only type of drug for which consistent, clear evidence of a beneficial effect on total cardiovascular events, total coronary events and stroke was available, was the statins. The greatest evidence was with simvastatin in people with a blood cholesterol level of at least 3.5 mmol/litre. The evidence on side effects was inconclusive in these trials.
Cochrane authors searched for clinical studies on 19 October 2017. We found five trials, including 612 women, that met the inclusion criteria. The studies took place in Egypt, the US, Japan and Italy. Only three of the included studies provided data in a format that could be analysed in this review. Combined oral contraceptive pill versus placebo We found two trials including 354 women that compared the COCP with a placebo (pretend treatment). The evidence was at high risk of bias. There was very low quality evidence that treatment with the COCP was associated with an improvement in self-reported dysmenorrhoea (period pain) at the end of treatment measure on a verbal rating scale (where the woman rates her pain as (for example) "no pain," "slight pain," "moderate pain," "severe pain" and "unbearable pain") and low quality evidence for an improvement in self-reported dysmenorrhoea pain at the end of treatment using a visual rating scale (where the woman marks her pain visually on a line) compared with placebo. There was very low quality evidence that there was a reduction in menstrual pain from the beginning to the end of treatment in the COCP group compared with women having a placebo. Combined oral contraceptive pill versus other medical treatment We found one trial of 50 women that compared the COCP with another medical treatment (goserelin). The study was at high risk of bias. At the end of treatment, the women in the goserelin group were not having a period and therefore we could not compare the groups. Six months after the end of treatment, there was very low quality evidence that there was no clear difference between women treated with the COCP and women treated with goserelin for self-reported dysmenorrhoea, using a visual rating scale or a verbal rating scale. Six months after the end of treatment, there was very low quality evidence that there was no clear evidence of a difference between the COCP and goserelin groups for reporting complete absence of pain, as measured by a visual rating scale and low quality evidence using a verbal rating scale. The quality of the evidence was very low quality. The main reasons for downgrading the evidence were because the data were based on a single small trial with wide variation in results and lack of details about how the study had been designed. There were some concerns with two of the studies that were funded by a pharmaceutical company that also had input into the design of the trial, data collection and the analysis of data. This means that we cannot be confident about the results.
This review found that sclerotherapy was better than surgery in terms of treatment success, complication rate and cost at one year, but surgery was better after five years. However, the evidence was not of very good quality and more research is needed.
We systematically searched and evaluated randomised controlled trials investigating the effectiveness of drug treatment for polydipsia. We found two short trials (n=17, duration 3-6 weeks) that were too small and short to be informative. Data reporting was also poor with no pre crossover data available for analysis. The only data available were for adverse effects and neither the active treatments nor placebo produced any serious side effects. The studies did not report any useful data on measures of polydipsia, physical symptoms secondary to increased fluid intake, mental state, general functioning or economic outcomes. Clinicians hoping to treat people with psychosis-related polydipsia are unable to gain any useful information from these trials and treatment of any sort might only be informative within a well-designed study. More research is needed and these two trials, although unable to provide much data, do show this type of research is possible.
This review is an update of all relevant randomised trials that have evaluated an intervention that aimed to reduce more than one risk factor (multiple risk factor intervention) in people without evidence of cardiovascular disease. The findings are from 55 trials of between six months and 12 years duration conducted in several countries over the course of four decades. The median duration of follow up was 12 months (with a range of six months to 12 years). Multiple risk factor intervention does result in small reductions in risk factors including blood pressure, cholesterol and smoking. Contrary to expectations, multiple risk factor interventions had little or no impact on the risk of coronary heart disease mortality or morbidity. This could be because these small risk factor changes were not maintained in the long term. Alternatively, the small reductions in risk factors may be caused by biases in some of the studies. The methods of attempting behaviour change in the general population are limited and do not appear to be effective. Different approaches to behaviour change are needed and should be tested empirically before being widely promoted, particularly in developing countries where cardiovascular disease rates are rising. Further trials may be warranted.
Only randomised controlled trials were included in this review. These are studies in which two groups of patients were compared, each group receiving a different form of SLT, with patients assigned to the groups in a random fashion to reduce potential for bias. Six trials were found with a total of 159 patients. Methods varied so much that meta-analysis of the results was not possible. Considering the small number of patients and the methodological flaws in these studies, there is insufficient evidence to support the use of one form of SLT over another for the treatment of speech problems in individuals with Parkinson's disease.
This review found that in the short term PPIs relieve heartburn better than H2RAs in patients who are treated without specific diagnostic testing. Although the difference is smaller, this is also true for patients with gastro-oesophageal reflux disease (GORD), who have a normal upper endoscopy . In summary, proton pump inhibitor drugs appear to be more effective than H2-receptor antagonists for relieving heartburn.
The evidence was updated until January 2013. We found five studies of children with asthma; of them, four studies, representing 559 children (aged six to 18 years) with mild to moderate asthma, contributed data to the review. No study enrolled pre-school children (i.e. aged under six years). Three studies compared the combination of anti-leukotrienes and ICS with the same dose of ICS alone; one study compared the combination of anti-leukotrienes and ICS to a higher dose of ICS; and no study tested whether the addition of anti-leukotriene to ICS could allow the tapering of the dose of ICS while maintaining asthma control. All studies used montelukast as the anti-leukotriene agent, which was administered for four to 16 weeks. Included studies enrolled both girls and boys and between 65% and 69% were boys. All trials enrolled children with mild to moderate airway obstruction. Whether comparing the addition of anti-leukotrienes to ICS to the same dose or an increased dose of ICS, there was no difference in the number of participants experiencing one or more moderate exacerbations (that is, requiring oral corticosteroids) or severe exacerbations (i.e. requiring a hospital admission). A single study comparing the same ICS dose reported lung function tests and showed no or small group differences depending on the test used. There is no firm evidence to support that adding montelukast to ICS is safe and effective to reduce the occurrence of moderate or severe asthma attacks in children taking low-dose ICS and whose symptoms remain uncontrolled. After being on the market for more than 10 years, the limited number of available studies testing antileukotrienes in children, the absence of data on preschoolers, and the inconsistency of available trials in reporting of efficacy and safety clinical outcomes is disappointing and limit the conclusions. This review is based on a small number of identified trials conducted in children with asthma; none were conducted in preschoolers. As a single study of moderate duration reported all measures of efficacy and most measures of safety, our confidence in the quality of evidence is low. Other important measures of asthma control were either not measured or reported in different formats, so they could not be pooled. In other words, there are too few paediatric trials to conclude firmly whether either treatment is superior to the other.
We searched for studies up to 19 October 2015, and we included 26 studies with 526 people. These people had breathlessness from different types of lung disease. Some were given opioid drugs and some were given other drugs or a placebo, and studies compared the reporting of breathlessness to see if there was any difference. Some studies also looked at the amount of time people could exercise to see if there were any differences. Some people came from home, and some came from the hospital setting. There was some low quality evidence that showed a benefit of using oral or injectable opioid drugs for the treatment of the symptoms of breathlessness. There was no evidence for opioids by nebuliser. Some people experienced drowsiness, nausea, and vomiting. More research is needed using more people, and looking at effects on quality of life. We rated the quality of the evidence using one of the following grades: very low, low, moderate, or high. Very low quality evidence means we are uncertain about the results. High quality evidence means we are very certain about the results. For this Cochrane review, we found that the evidence was of low to very low quality. We included randomised controlled trials which were blinded, which means that participants and those people that assessed the results did not know whether the participants had received the opioid drug or a placebo. However, the trials were of small size, and some studies did not give enough information to allow us to assess whether they were of good quality.
Through comprehensive search and screening of medical databases, we found two clinical studies that tested different treatments. One study, with 130 participants included, compared hyperfractionated radiotherapy (six-week course with treatment twice a day ) with conventional radiotherapy (six-week course with treatment once a day ). The second study, with 71 participants included, compared hypofractionated radiotherapy (three-week course with treatment once a day ) with conventional radiotherapy. For the comparison of hyperfractionated radiotherapy and conventional radiotherapy, there was no clear evidence of effect on OS, event-free survival (EFS; time from diagnosis, study entry, or treatment to disease progression, disease relapse, a second tumour, or death), radiological response (a reduction in tumour size of more than 50%), and toxicities (damage to the body due to radiotherapy). For the comparison of hypofractionated radiotherapy and conventional radiotherapy, there was no clear evidence of effect on OS, progression-free survival (PFS; time from diagnosis, study entry, or treatment to disease progression), and side effects. For the hyperfractionated radiotherapy, when compared with conventional therapy, the quality of evidence was low for OS and EFS, and very low for radiological response and toxicities. For the hypofractionated radiotherapy, when compared with conventional therapy, the quality of evidence was moderate for OS, and low for PFS and toxicities.
This review included four trials that involved 163 participants who were mainly active young adult males. All had had a primary (first time) anterior shoulder dislocation as a result of injury. Methodological quality of the trials was variable. Three trials found similar numbers returning to previous activities such as active military duties and sports. The other trial found significantly fewer people in the surgical group failing to attain previous levels of sports activity. Pooled results from the three trials that were reported in full (124 participants) showed that subsequent instability, either redislocation or subluxation (partial dislocation), was significantly less frequent in the surgical group. Half (17/33) of the conservatively treated patients with shoulder instability in these three trials opted for subsequent surgery. Function, measured in different ways in the four trials, was usually better in those treated surgically. The only complication of treatment reported was an infected joint in a surgically treated patient. This review found that highly active young people were less likely to have an unstable shoulder when treated surgically after an acute anterior shoulder dislocation.
Three clinical trials involving/completed by 113 babies were identified that compared double-lumen catheters to single-lumen catheters. None of the studies used triple-lumen catheters. All three trials found that use of a double-lumen catheter lowered the number of additional venous placements needed during the first week of life. The double-lumen catheters, however, clogged, leaked, and broke more often. In these studies, no significant difference was found in catheter placement difficulty and misplacement, catheter-related infections or blood clots, other serious complications, or rate of infant mortality. But the quality of studies was poor, and sample sizes were too small to draw valid conclusions about many complication rates. Available clinical trials at present do not provide a basis for recommending one catheter type over another in this setting.
The evidence was current to June 2014. We included randomised controlled trials (RCTs) looking at the effect flushing of the fallopian tubes (with either oil-soluble or water-soluble contrast media) has on live birth and pregnancy rates in women with subfertility. Such women were those who had not been able to conceive after at least six months of unprotected sexual intercourse. We also looked at the rates of adverse events, including miscarriage and ectopic pregnancy (a pregnancy growing outside the womb) after flushing the tubes. We included 13 RCTs (2914 women). The trials compared oil-soluble and water-soluble media with no intervention and with each other. We found evidence that tubal flushing with oil-soluble media may increase the chances of live birth and ongoing pregnancy, compared to no intervention. Our findings suggest that among subfertile women with a 17% chance of ongoing pregnancy if they have no intervention, the rate will increase to between 29% and 55% if they have tubal flushing with oil-based contrast media. We found no evidence of a difference between water-soluble contrast media and no intervention and the contrast media compared one against the other with respect to live birth and pregnancy, though there were few data for most comparisons. There was no evidence of a difference between any of the groups with respect to adverse events, but such events were poorly reported in most studies. The overall quality of the evidence was low or very low for all comparisons. The main limitations were imprecision, risk of bias and inconsistency. There were too few studies to evaluate the risk of publication bias.
Nine trials involving 1752 women were included in the review. The trials with low risk of bias found that phenobarbital given to women immediately prior to a very preterm birth did not decrease the risk of bleeding in the brains of the babies. No differences in child development were found on follow up at 18 to 24 months or at seven years. Maternal sedation was more likely in women receiving phenobarbital. The use of prenatal corticosteroids, known to reduce rates of periventricular haemorrhage, varied between trials and may have influenced findings.
The search for studies was done on 23 October 2014. One study (a randomized controlled trial) was found. There were 258 participants in the trial. These 258 people were randomly divided into two groups. One group received the optic nerve decompression surgery along with careful follow-up. The other group received careful follow-up alone. Careful follow-up included an ophthalmologic examination at each study visit and visual field testing at 12 months and as needed. The technician performing the follow-up tests did not know to which group the participants belonged (surgery or no surgery). Funding for this trial was provided by National Eye Institute, USA. The trial was stopped early because the surgery was not helping the participants more than careful follow-up alone. The trial found no evidence of benefit from the surgery, but there were several harms caused by the surgery, such as further vision loss. Pain and double vision were harms experienced by some participants in the surgery group at one week after the surgery. The trial investigators reported that continued enrollment would be unlikely to produce results in favor of surgery. The quality of evidence in this one trial is considered high.
We searched the scientific literature up to September 2014 and found seven relevant studies with 444 participants with these fractures. One study compared surgery with non-surgical treatment and the other six studies compared the use of different surgical implants. Each of the studies was small and was designed in a way that may affect the reliability of their findings. Most studies did not report on patient-reported outcomes measures of function. We judged the quality of the reported evidence was very low and thus we are not certain that these results are true. The study comparing surgical fixation with non-surgical intervention (traction and wearing a brace) did not confirm there was any difference between the two treatments in terms of re-operations or repeat traction and bone healing. However, there were more complications such as pressure sores associated with prolonged immobilisation in the traction group, who stayed on average one month longer in hospital. Five studies compared one type of nail versus one of three different types of plate fixation. One study compared locked with non-locked plate fixation. The evidence available for the four comparisons did not confirm that any of the surgical implants were superior to any other surgical implant for any outcomes, including re-operation for complications such as lack of bone healing and infection. The review found that the available evidence was very limited and insufficient to inform current clinical practice. Further research comparing commonly used surgical treatments is needed.
We included a total of 48 studies that involved 4937 participants and covered three types of programme: behavioural, cognitive-behavioural and multimodal. Overall, the results suggested statistically significant improvements in the short-term for parental depression, anxiety, stress, anger, guilt, confidence and satisfaction with the partner relationship. However, only stress and confidence continued to be statistically significant at six month follow-up, and none were significant at one year. There was no evidence of effectiveness for self-esteem at any time point. None of the studies reported aggression or adverse outcomes. Only four studies reported the outcomes for fathers separately. These limited data showed a statistically significant short-term improvement in paternal stress but did not show whether the parenting programmes were helpful in terms of improving depressive symptoms, confidence or partner satisfaction. This review shows evidence of the short-term benefits of parenting programmes on depression, anxiety, stress, anger, guilt, confidence and satisfaction with the partner relationship. The findings suggest that further input may be needed to support parents to maintain these benefits. However, more research is needed that explicitly addresses the benefits for fathers, and that provides evidence of the comparative effectiveness of different types of programme and identifies the mechanisms involved in bringing about change.
So far, virtual reality has been used in the assessment and treatment of a range of psychiatric disorders and social anxieties, some of which include, fear of flying, public speaking anxiety, spider phobia, and post-traumatic stress disorder. There are also a few studies that examine the emotional responses of people with schizophrenia during a computer simulation with characters displaying happy, neutral, and angry emotions. Virtual reality has also been used for people with schizophrenia in social skills training and to improve processes of thinking and understanding. This review investigates the effects of virtual reality in helping support the treatment and taking of medication for people with serious mental illness. The most recent search for randomised trials was run in September 2013, only three short studies with a total of 156 people could be included. People with schizophrenia were randomised to a) skills training sessions that used virtual reality to deliver the training or b) sessions of skills training using other methods to deliver the training or c) standard care. All evidence from the trials was low quality and no real effects were found. At present, there is no clear evidence for or against using virtual reality for encouraging people with mental illness to take their medication. If virtual reality is used for people with serious mental illness, it will be of an experimental nature.There is a need to gather more good quality information on the effects of virtual reality for people with mental illness and high quality studies need to be undertaken. At this stage, the effects of virtual reality are experimental, novel and innovative but largely untested. This summary has been written by a consumer, Ben Gray of RETHINK.
The search identified one study that tried to answer this question and was eligible for inclusion in the review. The study enrolled 132 people with cystic fibrosis, most of whom (82 people) had acute lung infections with Pseudomonas aeruginosa, and randomly put them into two treatment groups. In the first group two antibiotics were selected following the testing of combinations of antibiotics and in the second group the two antibiotics were chosen after testing individual antibiotics to see how effective the drugs were against the bacterium. The study was run across several centres and assessed the clinical outcomes in the participants after a 14-day course of treatment. The study investigators were only able to provide us with data for those who were infected with Pseudomonas aeruginosa for their main outcome (the time until the next acute lung infection). Choosing antibiotics based on the results of combination antibiotic testing did not lead to a longer time until the next lung infection compared to choosing antibiotics based on results of separate testing. They could not provide us with any results people infected with Pseudomonas aeruginosa for other outcomes in our review. We are satisfied that the people taking part were divided into the different treatment groups completely at random and no one could have foreseen which group any individual would be in. We are also satisfied that during the study, neither the individuals or clinic personnel knew which treatment group each individual was in. There were no missing data from the study. The quality of the evidence for the only outcome for which we have data (time to the next lung infection) is moderate, but we could not judge the quality of the evidence for other outcomes as there were no separate results available for people infected with Pseudomonas aeruginosa.
We included randomised clinical trials (where people are randomly put into one of two treatment groups) looking at the effects of paracetamol for people with hip or knee pain due to osteoarthritis against a placebo (a 'sugar tablet' that contains nothing that could act as a medicine). We found 10 trials with 3541 participants. On average, participants in the study were aged between 55 and 70 years, and most presented with knee osteoarthritis. The treatment dose ranged from 1.95 g/day to 4 g/day of paracetamol and participants were followed up between one and 12 weeks in all but one study, which followed people up for 24 weeks. Six trials were funded by companies that produced paracetamol. Compared with placebo tablets, paracetamol resulted in little benefit at 12 weeks. Pain (lower scores mean less pain) Improved by 3% (1% better to 5% better), or 3.2 points (1 better to 5.4 better) on a 0- to 100-point scale. • People who took paracetamol reported that their pain improved by 26 points. • People who took placebo reported that their pain improved by 23 points. Physical function (lower scores mean better function) Improved by 3% (1% better to 5% better), or 2.9 points (1.0 better to 4.9 better) on a 0- to 100-point scale. • People who took paracetamol reported that their function improved by 15 points. • People who had placebo reported that their function improved by 12 points. Side effects (up to 12 to 24 weeks) No more people had side effects with paracetamol (3% less to 3% more), or 0 more people out of 100. • 33 out of 100 people reported a side effect with paracetamol. • 33 out of 100 people reported a side effect with placebo. Serious side effects (up to 12 to 24 weeks) 1% more people had serious side effects with paracetamol (0% less to 1% more), or one more person out of 100. • Two out of 100 people reported a serious side effect with paracetamol. • One out of 100 people reported a serious side effect with placebo. Withdrawals due to adverse events (up to 12 to 24 weeks) 1% more people withdrew from treatment with paracetamol (1% less to 3% more), or one more person out of 100. • Eight out of 100 people withdrew from paracetamol treatment. • Seven out of 100 people withdrew from placebo treatment. Abnormal liver function tests (up to 12 to 24 weeks): 5% more people had abnormal liver function tests (meaning there was some inflammation or damage to the liver) with paracetamol (1% more to 10% more), or five more people out of 100. • Seven out of 100 people had an abnormal liver function test with paracetamol. • Two out of 100 people had an abnormal liver function test with placebo. High-quality evidence indicated that paracetamol provided only minimal improvements in pain and function for people with hip or knee osteoarthritis, with no increased risk of adverse events overall. None of the studies measured quality of life. Due to the small number of events, we were less certain if paracetamol use increased the risk of serious side effects, increased withdrawals due to side effects, and changed the rate of abnormal liver function tests. However, although there may be more abnormal liver function tests with paracetamol, the clinical implications are unknown.
We identified 25 randomised controlled trials. No two trials investigated the same antibiotics, and there was no standard treatment regime used as a comparison. We are not able to define the best treatment for cellulitis and our limited conclusions are mostly based on single trials. No single treatment was clearly superior. Surprisingly, oral antibiotics appeared to be more effective than antibiotics given into a vein for moderate and severe cellulitis. This merits further study. Antibiotics given by injection into a muscle were as effective as when given into a vein, with a lower incidence of adverse events. In one study the addition of corticosteroids to an antibiotic appeared to shorten the length of hospital stay, however further trials are needed. A single small study indicated vibration therapy may increase the rate of recovery but the results of single trials should be viewed with caution. We had insufficient data to give meaningful results for adverse events.
We included 128 trials with 8754 participants of both sexes aged between 33 and 76 years in the review and 94 trials with 5846 participants in the analysis. Three trials reported that their trial was officially registered. Trials included in the review were funded as follows: charity (n = 19), departmental resources (n = 8), governmental sources (n = 15) and industry (in part or in total) (n = 15). The source of funding was not specified for the other trials. We found that an epidural containing a local anaesthetic reduces the time required for return of gut function compared with an opioid-based regimen (equivalent to 17 hours). An epidural providing a local anaesthetic and an opioid also reduce pain (equivalent to a reduction of 2.5 on a scale from 0 to 10 for pain on movement at 24 hours after surgery) and time spent in hospital for open surgery (equivalent to one day). We found no evidence that an epidural with a local anaesthetic would affect the incidence of vomiting or poor healing of the gut. We rated the quality of the evidence as high for return of gastrointestinal function, moderate for pain treatment, low for no effect on vomiting or healing of the gut and very low for reduced time spent in the hospital after open surgery.
We collected and analysed all relevant studies to answer the review question and found 10 studies enrolling 1467 infants. In all studies, babies were born before the due date (from 23 to 36 weeks of gestational age). The sustained inflation lasted between 15 and 20 seconds at pressure between 20 and 30 cmH₂O. Most studies provided one or more additional sustained inflations in cases of poor clinical response, for example persistent low heart rate. We analysed one study (which included only nine babies) separately because researchers combined use of sustained or standard inflations with chest compressions, an additional intervention that might help babies begin normal breathing. The included studies showed no important differences among babies who received sustained versus standard inflations in terms of mortality, rate of intubation during the first three days of life, or chronic lung disease. Babies receiving sustained inflation at birth may spend fewer days on mechanical ventilation. The results of several ongoing studies might help us to determine whether sustained inflations are beneficial or harmful. At present we cannot exclude small to moderate differences between the two treatments. The quality of evidence is low to moderate because only a small number of studies have looked at this intervention, few babies were included in these studies and some studies could have been better designed. We searched for studies that had been published up to April 2019.
We included 77 randomised clinical trials in this review, which tested 75 herbal medicines. All trials had high risk of systematic errors (ie, bias or risk of overestimation of benefits and overestimation of harms) as well as high risks of random errors (ie, play of chance) due to the small number of people in the trials. Herbal medicines tested in the randomised clinical trials included single-herb products (Gynostemma pentaphyllum,Panax notoginseng, andPrunus armeniaca), commercially available branded herbal medicines, and combination formulas prescribed by practitioners. Herbs most commonly included as an ingredient in different products wereCrataegus pinnatifida,Salvia miltiorrhiza,Alisma orientalis,Bupleurum chinense,Cassia obtusifolia,Astragalus membranaceous, andRheum palmatum. We could not combine the results of the trials due to the range of different herbs used. We could not reach any conclusions about the use of herbal medicines for people with fatty liver disease as none of the trials reported results on death, liver-related illnesses, quality of life, or costs. A number of trials showed positive effects of herbal medicines compared with control interventions on enzyme activity (enzymes are proteins that cause chemical reactions in the body; eg, serum aspartate aminotransferase, alanine aminotransferase, glutamyltransferase, alkaline phosphatases), ultrasound scan findings, and computed tomography scan findings. No serious adverse effects were reported for herbal medicines. However, the methodology of the trials had high risk of systematic errors (bias). Furthermore, the individual herbs were seldomly retested, and all trials had relatively low numbers of people, which increases the risk of random errors (play of chance). Therefore, the findings are inconclusive, and rigorously conducted randomised clinical trials are required to establish the benefits and harms of herbal medicines for fatty liver disease.
The authors found two small heterogeneous randomised trials that investigated the effect of inspiratory muscle training. These studies do not provide enough evidence to draw any conclusions about the effect of inspiratory muscle training for patients with stroke. There is also no evidence relating to the safety of inspiratory muscle training. Future well-designed studies are needed.
We found six clinical trials with 1214 people. A single 120 mg dose of etoricoxib produced useful pain relief in 7 in 10 (66%) people with moderate or severe pain, compared with just over 1 in 10 (12%) with placebo. A single 90 mg dose produced similar results in one large trial. Pain relief lasted for 20 hours in half of people treated. Adverse events occurred at similar rates with etoricoxib and placebo in these single-dose studies. No serious adverse events or withdrawals due to adverse events occurred with etoricoxib.
We performed a systematic review looking at all randomized clinical trials evaluating stage II colon cancer patients and adjuvant therapy versus surgery alone. Our review found that adjuvant therapy -either systemic or regional chemotherapy or immunotherapy- can improve the outcomes of stage II patients. In counselling individual patients, the advice given should be conditioned by the patient's age and comorbidities. In addition, the high risk features of the tumour should also be considered when contemplating the benefits of systemic therapy in patients with stage II colon cancer. Further investigation is needed to elucidate which patient and tumour factors can be used to select stage II colon cancer patients for adjuvant therapy. There also exists a need to continue to search for other adjuvant therapies which might be more effective, shorter in duration and less toxic than those available today.
We searched all relevant studies that involved financial interventions directed at smokers and healthcare providers. For smokers, the aim of the healthcare financing interventions had to be to encourage the use of smoking cessation treatment or making successful quit attempts. For interventions directed at healthcare providers, the intervention had to stimulate the healthcare provider to assist people with quitting smoking, for example by prescribing smoking cessation treatment. For the update of this review, we searched studies on the effect of financial interventions on smoking cessation treatment and success in September 2016. We found six new relevant studies, resulting in a total of 17 studies. We found 15 studies directed at smokers. Covering all the costs of smoking cessation treatment for smokers (free treatment) when compared to providing no financial benefits increased the number of smokers who attempted to quit (4 studies, 9065 participants), used smoking cessation treatments (7 studies, 9455 participants), and succeeded in quitting (6 studies, 9333 participants). We found three studies directed at healthcare providers. The two studies that investigated the effect of a financial intervention on quit success (2311 participants) did not clearly show an increase in quit rates. Financial interventions directed at healthcare providers also did not have an effect on the use of smoking cessation medication (2 studies, 2311 participants). However, financial interventions did increase the number of smokers who used smoking cessation counselling (3 studies, 25,820 participants). Information on the costs of the intervention was available for eight studies (33,488 participants). The economic evaluation of the individual studies showed that although the absolute differences in quitting were small, the costs per person successfully quitting were low or moderate. We concluded that financial interventions directed at smokers increase the proportion of smokers who attempt to quit, use smoking cessation treatments, and succeed in quitting. We did not detect a clear effect on smoking cessation from financial incentives directed at healthcare providers. This review has some limitations that affect how confident we can be in the conclusions. The included studies varied substantially in quality and in methods and design, which makes it difficult to compare results.
We searched for trials involving participants of any age or sex, who underwent an emergency operation to treat penetrating abdominal trauma. The evidence is current to 23 July 2019. We included 29 studies that included 4458 participants. There were problems with the design and conduct of all of these studies, which means that we were uncertain about the results. Most of these studies were carried out over 20 years ago, using antibiotics that are not often used today. Surgical techniques and practice have also evolved substantially during this time. Seven out of the 29 studies received funding from pharmaceutical companies, whilst the other studies did not state their funding sources. Because of the very low-quality of the evidence, we are uncertain whether giving longer courses of antibiotics after penetrating injury reduces the rate of infections after an operation. We are also uncertain if one antibiotic treatment is better than any other that was tested in the trials. The quality of evidence for all outcomes was very low, mainly due to problems with the way the studies were run. These problems were not using placebos (medications that look identical to the study drug but do not contain the active ingredient), a lack of blinding of both participants or the investigators or inadequate methods of randomly allocating treatments to the participants. There were also key differences in the methods used between the studies. New, better quality studies are required in order to answer questions about the use of antibiotics to reduce infections following penetrating abdominal injury.
Nine studies were included; however only five studies provided sufficient information for the analysis (86 participants receiving pulmonary rehabilitation and 82 participants not receiving pulmonary rehabilitation). Three studies included only people with IPF, and the other six studies included people with a variety of ILDs. The average age of participants ranged from 36 to 71 years. No reports described unwelcome effects of pulmonary rehabilitation. Immediately following pulmonary rehabilitation, participants could walk farther than those who had not undertaken pulmonary rehabilitation (on average, 44 metres farther in six minutes). Participants also improved their maximum exercise capacity and reported less shortness of breath and improved quality of life. People with IPF also experienced improvements in exercise capacity, dyspnoea and quality of life following pulmonary rehabilitation. Information was insufficient to establish whether ongoing effects were noted once pulmonary rehabilitation had stopped. Because of inadequate reporting of methods and small numbers of participants, the quality of evidence was low to moderate. This Cochrane plain language summary is current to June 2014.
We identified 67 studies, which included 3632 women with ovarian cancer and were published between 1966 and 2017. The most frequently described strategy was administration of antibodies targeting the tumour antigen CA-125 (2347 participants in 17 studies). Most of these studies primarily evaluated safety and immunological responses. Severe flu-like and gastrointestinal symptoms occurred in 7% to 30% of participants. Researchers frequently detected antibodies and immune cells recognising the tumour antigen CA-125, albeit response rates varied between studies. Despite these promising immunological responses, four large studies reported no survival advantage for participants treated with CA-125-directed antibody over those given placebo. For strategies not relying on antibody administration, similar conclusions cannot yet be drawn. Overall, study authors report that treatment was well tolerated and inflammatory side effects at the injection site were most frequently observed. Researchers observed responses of the immune system for most strategies studied, but the clinical benefit of these strategies remains to be evaluated in large trials. Because no high-certainty evidence of clinical benefit is currently available, antibody therapy targeting CA-125 should not be incorporated into standard treatment in its current form. Based on lack of uniformity in included studies, we strongly advocate universal adoption of response definitions, guidelines for adverse events reporting, and directives for trial conduct and reporting. Furthermore, results from ongoing randomised controlled trials (RCTs) are awaited, and further RCTs should be conducted.
In this review we assessed the effect of these agents on erectile dysfunction in diabetic people. Eight studies with 976 men randomised to PDE-5 inhibitor therapy and a duration of mainly 12 weeks were evaluated. Compared to placebo treatment, these agents showed favourable effects in scores estimating sexual life, with an increased rate of adverse effects like headache and flushing after PDE-inhibitor therapy. Mortality was not reported in any of the included trials. Quality of life, with the exception of scores for sexual life, was not relevantly affected. If taken as prescribed, PDE-5 inhibitors comprise a valuable treatment option for erectile dysfunction in men with diabetes.
Six multicentre, well designed pre-market studies including 5640 participants were eligible for this review. Pooling analysis did not performed in four trials due to the data not similar enough, but conducted for two trials. Topotecan appears to have a similar level of effectiveness as paclitaxel, topotecan plus thalidomide, and superior than treosulfan, but shorter overall survival than pegylated liposomal doxorubicin. Topotecan delays progression of disease than paclitaxel, treosulfan; topotecan plus thalidomide superior than topotecan alone on PFS, but topotecan alone significantly shorter than topotecan plus thalidomide. Further consolidation treatment with topotecan does not improve PFS for participants with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel. Evidence from three studies were high quality, remain four studies were low or moderate due to poor reporting of the methodology. For gaining the better representativeness, more large, well-designed randomised controlled trials of post-market drug are required in the future.
We identified two studies that evaluated beta-blockers giving during surgery (perioperatively) in people undergoing major non-cardiac vascular surgery, with follow-up data on cardiovascular outcomes. A total of 599 participants were randomised to receive beta-blockers (301 participants) or placebo (298 participants). Both studies were double-blind (neither participants nor surgeon were aware of the treatment), randomised controlled trials evaluating the beta-blocker, metoprolol. The results of the analysis offered no clear evidence that perioperative beta-blockers reduced death from any cause (all-cause mortality), cardiovascular death, non-fatal heart attack, irregular heartbeat (arrhythmia), heart failure, stroke, combined cardiovascular events or re-hospitalisation at 30 days. There was evidence to support that beta-blockers increased the risk of intra-operative low heart rate (bradycardia) and low blood pressure (hypotension). These complications should be weighed with any benefit when considering the use of beta-blockers in this population. Study quality was good for both trials. One trial did not adequately describe their randomisation techniques and the other trial did not report whether the outcome assessors were blinded to the treatment group, and was possibly underpowered. With only two studies included, several of the outcomes only had data from a single study, and neither of the studies reported on blockage or obstruction of blood vessels (vascular patency/graft occlusion), reducing the quality of evidence to moderate.
Five trials were identified from a systematic search of the literature which were of high enough quality to be included in the review. These trials involved 787 participants in total. We were able to combine the results from two trials (114 participants) and there was no significant difference between the corticosteroid and control groups in the presence of postherpetic neuralgia six months after the onset of the acute herpetic rash. Two of the three other included trials reported results at less than one month, so these participants did not fulfil the current criteria for a diagnosis of postherpetic neuralgia. The last trial reported results in a format unsuitable for meta-analysis. There were no significant differences in serious or non-serious adverse events between the corticosteroids and placebo groups. There was also no significant difference between the treatment groups and placebo groups in other secondary outcome analyses and subgroup analyses. It can be concluded that, based on moderate quality evidence, corticosteroids are not effective in preventing postherpetic neuralgia.
The reviewers evaluated the safety and effectiveness of a drug called terlipressin: they reported that terlipressin appears to be as safe as other treatments and that terlipressin may reduce the mortality from variceal bleeding as compared to placebo. The reviewers did not have sufficient data to decide whether terlipressin was better or worse than other available treatments such as other drugs (somatostatin, octreotide) or endoscopic treatment.
This review did not find robust evidence that oral calcium supplementation reduces high blood pressure in adults. It reviewed 13 trials enrolling 485 people, which compared calcium supplementation with placebo or no treatment, and measured blood pressure 8 to 15 weeks later. On average, people receiving extra calcium achieved slightly lower systolic blood pressure at the end of trials. However, most trials were of poor quality, so their results may not be reliable. Trials were too small and short to measure whether extra calcium reduces the risk of death, heart attack or stroke. Calcium usually had no more adverse effects than placebo. Larger, longer duration, better quality trials are needed to clarify whether calcium supplementation can lower high blood pressure.
Eleven scientific studies were analysed to derive the best available evidence. The majority of the studies included newborn babies born after 32 weeks' gestation. The main outcomes assessed were drug levels in the blood and kidney functions. The search was updated to 29 April 2016. Safer and potentially more effective levels of the drug were maintained using a 'one dose per day' treatment schedule. No differences in the risk of adverse effects on the kidney function or hearing were noted between two regimens. The quality was evidence was considered as moderate because the sample size was relatively small and two of the studies were scientifically less robust.
We performed a rigorous search of the medical literature in October 2016 and found three studies that compared a single treatment session of BtA with BtB. These studies included a total of 270 participants, with on average a moderate disease impairment. The participants remained in the studies for a short period of time - between 16 and 20 weeks after the treatment. The average age of people in the studies was 53.3 years, and they had had cervical dystonia for an average of 6.6 to 7.9 years before taking part in the trials. Most, 63.3%, of the people in the studies were women. All three of the studies were funded by drug manufacturers with possible interests in the results of the studies. The results show little or no difference between BtA and BtB in the main measures of overall improvement and safety, including the total number of adverse (unwanted or harmful) events. There was also little or no difference between BtA and BtB in the self-evaluations reported by the study participants. Based on the results we would expect that, out of 1000 people with cervical dystonia treated with BtB, there would be 362 more people who experience dry mouth/sore throat compared to 1000 people treated with BtA. The studies which looked at the duration of effect showed little or no difference between BtA and BtB. None of the studies examined the impact of either Bt on quality of life. All of the studies included participants that were different to the average person who suffers from cervical dystonia. To be included participants had to have a history of successful treatment with Bt. People with certain types of cervical dystonia, in particular the forms that make the head turn backward or forward, were not allowed to participate in the studies. Not enough participants were included across the studies for us to be completely confident in the results for the total number of adverse events, the self-reported evaluations by participants or the pain assessment. The quality of the evidence for overall improvement and total number of adverse events was low. The quality of the evidence for more sore throat/dry mouth in people receiving BtB is moderate. The quality of the evidence where participants gave their self-assessments is low. No definite conclusions can be drawn regarding overall safety and long-term utility of BtA compared to BtB in cervical dystonia.
The evidence is current to August 2017. We searched the literature and found a total of 2554 citations that were potentially relevant. After reviewing each of these, we found 11 articles describing clinical trials that could help us answer our question. Taken together, these trials included 12,944 adult participants who suffered cardiac arrest either in-hospital or out-of-hospital. The newest studies identified in this update are larger and of higher quality than those that had been identified in prior versions of this review. Several studies were sponsored by device manufacturers. We found that available studies have important differences from one another. The most important differences were the type of mechanical device studied and the type of CPR protocol provided for patients assigned to the manual chest compression group. These differences make comparisons across studies challenging. Some studies reported improvements in rate of survival for patients treated with mechanical chest compressions compared to patients treated with manual chest compressions, while others reported no difference or even suggested harm associated with mechanical chest compressions. When considering all of the identified studies together, it seems like mechanical chest compression devices probably have a very similar effect on survival when compared with high-quality manual chest compressions. With the inclusion of several large studies, the overall quality of evidence has improved considerably, and now may be considered to be of low to moderate quality.
We searched medical databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) of adults or children with epilepsy, where a ketogenic diet was compared with other treatments. We found 11 randomised controlled trials, with 778 participants. The trials were between two and 16 months long. The short-term side effects of ketogenic diets included diarrhoea, constipation and vomiting. Long-term effects are unknown from these studies. All studies reported participants dropping out, due to lack of improvement in seizures and poor tolerance of the diet. One study reported upon the effect of ketogenic diets on quality of life, cognition and behaviour. No difference was found in the quality of life of those following a ketogenic diet and the group receiving care as usual, but participants following the ketogenic diet were found to be more active, more productive and less anxious. More research is needed in these areas. Recently, other, better tolerated, ketogenic diets, such as the modified Atkins diet, found similar effects on seizure control as those more restrictive ketogenic diets. However, more research is required. The studies included in this review were limited by small numbers of participants and only children were included in 10 of the 11 studies, therefore, we judged the quality of the evidence to be low to very low. There is little research at present into the use of these diets in adults, therefore, more research is required in this area. This evidence is current to April 2017.
This review found one good quality study of cidofovir (an antiviral agent) injected into the warts at the time of surgical removal. After one year of treatment, however, this study found no benefit of the injected cidofovir when compared to injected salt water solution (placebo). There is still a need for a larger randomised study which includes more patients, and higher doses of cidofovir.
We included two studies involving 252 children with AOM, aged from three months to six years, receiving hospital ambulatory care. Children were treated with an antibiotic injection and either oral corticosteroid or a placebo (treatment with no effect). In one study, fluid from the middle ear was collected by inserting a needle through the eardrum to measure the level of inflammation. The National Institutes of Health (NIH) and the National Center for Research Resources, NIH, US Public Health Service funded both studies. Pharmaceutical companies provided the drug but did not contribute any other scientific or financial support. Corticosteroids did not make a significant difference in improving the symptoms and inflammation of the eardrum(s) at Day 5 and Day 14, but we are unsure of this effect due to the small numbers of children in the studies. There were no significant differences between the corticosteroid and placebo groups in terms of resolving fluid in children's middle ears (at 1, 2, and 3 months) and experiencing new episodes of AOM (at 1, 2, 3 months, and 4 and 6 months). Neither study reported a reduction in the duration of overall or specific symptoms, rupture of eardrum(s), the occurrence of middle ear inflammation in the other ear following the current ear infection, or serious complications. Only one study reported the overall side effects identified during the trial (e.g. drowsiness, dry mouth, diaper rash, nervousness). We could not draw any conclusions regarding the effects of corticosteroids for AOM in children. The quality of evidence included in this review was low to very low due to few children included in two small studies. We are uncertain about whether or not corticosteroids are useful in relieving pain from AOM.
This review found results from one arm of a trial only involving a very small number of patients. The results suggest that endovascular treatment can be carried out with a high degree of technical success at the time of treatment but there is insufficient evidence to determine whether the risk benefit ratio favours endovascular intervention over conservative management. Randomised trials need to be designed to determine whether the endovascular treatment is more successful than conservative treatment at reducing the long term risk of stroke or death.
In January 2012, we did a computer search for studies of birth control pills and acne treatment. Outcomes could be the amount of acne, how severe the acne was, and how many women dropped out early due to problems. We wrote to researchers to find other trials. We included randomized trials in any language that compared two types of birth control pills, a pill and a placebo or 'dummy,' or a pill and another acne treatment. The review now includes 31 trials with a total of 12,579 women. Ten studies used dummies. Overall, 24 pairs of treatments or placebos were compared: 6 compared a birth control pill and a placebo, 17 compared different types of birth control pills, and 1 compared a pill and an antibiotic. The six pills studied in trials with placebos worked well to reduce facial acne. When we compared pills with different hormones, we did not see any important and consistent differences. The conclusions did not change when we added trials in this update. Most trials compared two types of pills for acne treatment. Better quality studies are needed to compare one birth control pill with another. Studies should use standard methods for reporting how severe the acne is. How birth control pills compare to other acne treatments like antibiotics is not clear. Since birth control pills improve acne, they can be used to treat women with acne who also want birth control.
We included three studies with 124 participants in this review, but the quality of these studies was not ideal. All of the participants in the studies had tumours of the parotid glands and were undergoing surgery to part of the glands. The studies assessed two types of grafts, tissue obtained from the sternocleidomastoid muscle and a biomaterial (a collagen framework without cells). Two studies compared a tissue graft obtained from the sternocleidomastoid muscle to no graft. It is not known whether this type of tissue graft can prevent Frey's syndrome because the available evidence is very uncertain. One study compared a biomaterial graft to no graft. This type of graft may result in little or no difference to the incidence rate of Frey's syndrome, but the evidence is very uncertain. It may make the patient's wound slightly more likely to become infected. The evidence in this review is mostly of low or very low certainty, because of the small number of studies on this question and the risk of bias in these studies. The findings must therefore be treated with caution and further studies are needed to draw reliable conclusions. The evidence in this review is up to date to 5 February 2019.
We found 59 relevant studies, conducted between 1986 and 2015, involving 7667 participants undergoing elective surgery. Seven of the trials were conducted in 727 children. The PC6 acupoint stimulation varied from invasive techniques, such as traditional acupuncture needles, to noninvasive techniques, such as acupressure wristbands. PC6 acupoint stimulation was compared with six different types of antiemetic drugs (metoclopramide, cyclizine, prochlorperazine, droperidol. ondansetron and dexamethasone). Effects of PC6 acupoint stimulation versus sham on PONV We found a moderate-size effect in children and adults, although there were concerns about study limitations and unexplained variation in the effects. Further studies with sham comparisons are not necessary to confirm this beneficial effect. Effects of PC6 acupoint stimulation versus antiemetic on PONV We found no difference in the incidence of PONV. We rated the quality of this evidence as moderate, due to study limitations. Further studies are unlikely to show a difference. Effects of combining PC6 acupoint stimulation and antiemetic versus antiemetic on PONV We found a moderate-size effect on postoperative vomiting but not on postoperative nausea. However, there were concerns about study limitations, unexplained variation in effects between studies, and an insufficient number of studies. Further high-quality research on combinations of PC6 acupoint stimulation and antiemetics are needed to reduce uncertainties about this effect on PONV. Overall, the side effects related to PC6 acupoint stimulation were minor, transient and self-limiting (e.g. skin irritation, blistering, redness and pain) in 14 studies. To prevent PONV, the effect of PC6 acupoint stimulation is comparable to antiemetics.
This review identified 14 randomised controlled trials involving 5,500 women addressing this question. The analyses revealed no difference in overall survival and disease-free survival for women who received either preoperative or postoperative chemotherapy. Preoperative treatment makes more breast-conserving surgery possible because of shrinkage of the tumour before surgical intervention (relative risk, 0.82; 95% confidence interval, 0.76 to 0.89). However, this also results in a increase of loco-regional recurrence (recurrence in the same area) rate (hazard ratio, 1.12; 95% confidence interval, 0.92 to 1.37). Preoperative chemotherapy provides the possibility of monitoring tumour response and making appropriate regimen changes once the tumour appears to be resistant to the primary therapy. Adverse effects, which were reported in only half of the studies, were fewer in women receiving preoperative chemotherapy. Although, postoperative complications, nausea and vomiting, and alopecia were equally distributed, events of cardiotoxicity were less likely (relative risk, 0.74; 95% confidence interval, 0.53 to 1.04) in women receiving preoperative chemotherapy. Also, serious infection (analysed in 2799 women) was less likely to occur in women receiving preoperative chemotherapy (relative risk, 0.69; 95% confidence interval, 0.56 to 0.84).
We identified 12 studies which were suitable for use in the review. However, each study had some problems in the way that it was carried out. These problems make it difficult to be certain about the usefulness of MDRPs. Overall, the reviewed articles suggest that MDRPs are more likely to help patients cope with their physical needs than their emotional needs. MDRPs which looked at one specific behaviour area, such as diet, physical activity or stress, appeared to be more helpful for patients than programmes which attempted to address several different behaviours. Successful MDRPs usually involved face-to-face contact between a patient and a health professional (usually a nurse or physical therapist) and included at least one follow-up phone call. Programmes which took place over longer time periods (more than six months), or which were delivered by a specific type of health professional, or were delivered to a single cancer site were not more successful than brief, focused MDRPs delivered to mixed groups of cancer patients.
Six studies were identified for inclusion (four cluster RCTs, one CBA and one ITS). Four of these studies were conducted in sub-Saharan Africa, one in India and one in Pakistan. IRS reduced malaria transmission in young children by half compared to no IRS in Tanzania (an area where people are regularly exposed to malaria), and protected all age groups in India and Pakistan (where malaria transmission is more unstable and where more than one type of malaria is found). When compared with ITNs, IRS appeared more protective (according to the outcome chosen) in one trial conducted in an area of stable malaria transmission, but ITN seemed to be more protective than IRS in unstable areas. Unfortunately, the level of evidence is very limited and no firm conclusions should be drawn on the basis of this review. In conclusion, although IRS programmes have shown impressive success in malaria reduction throughout the world, there are too few well-run trials to be able to quantify the effects of IRS in areas with different malaria transmission, or to properly compare IRS and ITN.  High-quality and long-duration trials on a large scale, done in areas where there has been little or no mosquito control are still urgently required. New trials should include an IRS arm and an ITN arm, and should also assess the combined effect of ITN and IRS, a very important question in view of malaria elimination.
Several eating disorder prevention programs have been developed and trialled with children and adolescents. There is currently limited evidence in the published literature to suggest that any particular type of program is effective in preventing eating disorders and there has been concern that some interventions have the potential to cause harm. The aim of this systematic review is to determine whether these interventions are effective in the prevention of eating disorders in children and adolescents. Only one statistically significant result was found in the present meta-analysis - a slight effect of media literacy and advocacy programs in reducing acceptance of societal body image ideals. There is not sufficient evidence to suggest that harm was caused by any of the 12 randomised controlled trials included in the review at short-term follow-up. The meta-analysis is in the process of being revised to account for the impact of cluster randomised trials.
After extensive searching up to May 2015 to find all relevant medical studies that might provide evidence about whether NPWT is an effective treatment for leg ulcers, we found only one randomized controlled trial (RCT) that was eligible for this review. (RCTs provide more robust results than most other trial types.) The study was small with 60 participants who had hard-to-heal ulcers. The average age of these participants was 73 years, and 77% of them were women. The study was funded by the manufacturer of the NPWT machine. The study explored the use of NPWT in preparing leg ulcers for a skin graft. In the study, the ulcers were treated with NPWT or with normal (standard) care until the wounds were considered ready to have a skin graft applied. The study's results are not relevant for leg ulcers that are not being prepared for skin grafts. Participants remained in hospitals during treatment and until their wounds healed. There was low evidence from this study that ulcers treated with NPWT healed more quickly than those treated with standard care (dressings and compression). There was also evidence that ulcers treated with NPWT became ready for skin grafting more quickly than those treated with standard care. There were very limited results for other outcomes such as adverse events (harms) and it was not clear how information about adverse effects was collected. Twelve ulcers recurred (broke out again) in the NPWT group and 10 recurred in the standard care group. The evidence for the effectiveness of NPWT in treating leg ulcers is very limited, and at present consists of only one study with 60 participants. This study provided evidence that NPWT may reduce time to healing as part of a treatment that includes a skin graft. At present, no RCTs have investigated the effectiveness of NPWT as a main treatment for leg ulcers. This plain language summary is up-to-date as of May 2015.
The review found that the relevant six studies varied in significant ways: how severe the patients’ symptoms were; the form and intensity of the enhanced care offered. These differences made the studies difficult to compare. Many people left the studies before the outcomes could be measured. Given these problems with comparing existing research, it is only possible to say: enhanced care may help people with functional somatic symptoms; more intensive enhanced care may be more effective than very brief interventions. Further research into this topic is needed to test how much and what type of enhanced care could be effective. Future research should take into account barriers that might prevent such treatments benefitting patients. These include: GPs’ lack of time or skills, and their low expectations that enhanced care might help patients; patients’ reluctance to accept non-physical understandings of somatic symptoms.
We searched for evidence from randomised controlled trials on hyperbaric oxygen therapy in adults with moderate to severe Bell's palsy. Our searches revealed no trials that met the inclusion criteria for the review. We found very low quality evidence from one trial to suggest that hyperbaric oxygen therapy might be beneficial for moderate to severe Bell's palsy. The trial involved 79 participants and compared hyperbaric oxygen therapy to prednisone, a corticosteroid, which is a proven active treatment. The participants did not know which treatment they were being given. Those treated with hyperbaric oxygen recovered more quickly and recovered normal facial movement more often (95% versus 76%). All participants tolerated the treatment well, and there were no major complications. The quality of evidence from this trial was very low because the assessors of facial function were aware of which treatment each participant had been given, which introduces a high risk of bias. There is therefore no high quality evidence on which to base conclusions about the efficacy of hyperbaric oxygen therapy in Bell's palsy.
In this review we present data from meta-analyses that show (among other things) a decrease in glycated haemoglobin, fasting and post-load blood glucose and post-load insulin. But we found no evidence for an effect on mortality or morbidity. We found clues that with higher dosages the effect on glycated haemoglobin, in contrast to post-load blood glucose, remains the same. This might be because a lower compliance due to increasing side-effects.
. The review includes two small randomised studies with a total of 30 people with schizophrenia who had also developed antipsychotic-induced tardive dyskinesia. Participants in one study received either the anticholinergic drug procyclidine or isocarboxacid, an antidepressant drug. One participant group in the other study was withdrawn from the anticholinergic drug biperiden whereas the other group of participants continued taking biperiden. . There were sparse findings from two small and poorly reported trials. It is uncertain whether giving anticholinergic drugs is helpful in the treatment of tardive dyskinesia for people who are taking antipsychotic medication. It is also uncertain whether the withdrawal of anticholinergic medication improves the symptoms of tardive dyskinesia. . Available evidence is very low or low quality, limited, and small scale. It is not possible to recommend these drugs or the withdrawal of these drugs as a treatment for tardive dyskinesia. To fully investigate whether the withdrawal of anticholinergic drugs has any positive effects for people with tardive dyskinesia, we need more high quality research data. This plain language summary was adapted by the review authors from a summary originally written by Ben Gray, Senior Peer Researcher, McPin Foundation (mcpin.org).
We found five published randomised trials, none of which showed a statistically significant difference in overall survival for patients who had either narrow or wide removal of the melanoma and surrounding tissue.  Similarly, our meta-analysis showed there was no statistically significant difference in overall survival between the two groups treated with either narrow or wide excision. The summary estimate for overall survival favoured wide excision by a small degree, but the result was not significantly different. This result is compatible with both a 5% relative reduction in overall mortality favouring narrower excision and a 15% relative reduction in overall mortality favouring wider excision. Current randomised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma.
The evidence reviewed is current to August 2016. We included nine studies with a total of 407 participants in the review. All of the participants had asthma. In three of the nine studies, the participants also had a diagnosis of anxiety or depression, or both. The CBT was given either individually or in a group and ranged from four to 15 sessions. Participants given CBT had improved scores on the Asthma Quality of Life Questionnaire (AQLQ) and on measures of asthma control compared to participants who did not receive CBT. The studies generally did not report whether CBT reduced the likelihood of people needing oral steroids for an asthma attack. The benefit on AQLQ score was sustained up to a year after receiving CBT. Participants given CBT also had better anxiety scores compared to those given usual care. Participants given CBT did not have clearly improved depression scale scores or medication adherence. The overall quality of evidence presented is low due to the small number of studies included in the review, the differences in the design of the studies and in how the CBT was conducted, and because the participants knew to which treatment group (CBT or no CBT) they had been assigned.
We included six trials in this review, with a total number of 3847 participants. In all the trials, one group received IPT and the control group received placebo. Three trials were done in low malaria endemicity areas and the other three in high endemicity areas. In some trials, iron supplements were also given to children, which is also a treatment for anaemia, and we took this into consideration when analysing the data. Our results did not find that the number of children who died or were admitted to hospital was lower in the group receiving IPT, irrespective of whether they received iron (moderate quality evidence); and there was no difference in the number of children with anaemia at the end of follow-up (moderate quality evidence). Average haemoglobin levels were higher in the IPT group compared to the placebo group, but the effect was modest (low quality evidence). Although our results show that there are small benefits in haemoglobin levels when treating anaemic children with IPT, we did not detect an effect on death or hospital admissions. However, three of the six included trials were conducted in low endemicity areas where malaria transmission is low and thus any protective effect is likely to be modest.
This Cochrane review looked at trials comparing antibiotic regimens with atypical coverage to those without, limited to hospitalized adults with CAP. We included 28 trials, involving 5939 patients. For the regimens tested, no advantage was found for regimens covering atypical bacteria in the major outcomes tested - mortality and clinical efficacy. There was no significant difference between the groups in the frequency of total adverse events, or those requiring discontinuation of treatment. However, gastrointestinal events were less common in the atypical arm. There are limitations to this review in that a single study compared the addition of the atypical antibiotic to a typical antibiotic, the major question in clinical practice; most compared a single atypical antibiotic to a single typical antibiotic. Seventeen of the 27 trials were open label, 21 of the 27 studies were sponsored by pharmaceutical companies of which all but one was conducted by the manufacturer of the atypical antibiotic.
Our review included nine small trials, involving a total of 219 participants. Two trials compared HBOT versus sham therapy on ankle sprain and knee sprain respectively. Neither trial provided sufficient evidence to determine if HBOT helped people with these injuries. The other seven trials examined the effect of HBOT on muscle injury following unaccustomed exercise. There was no evidence that HBOT helped people with muscle injury following unaccustomed exercise, but some evidence that people given HBOT had slightly more pain. Further research on HBOT is not a high priority given the variety of other treatment interventions available.
One trial in 696 children assessed the benefits of injecting inactivated influenza vaccine (inactivated virus vaccines are the type currently used in the US and UK and cannot cause flu). There were no significant differences in the number of people experiencing an asthma attack (worsening of symptoms); however, there were better symptom scores (people reporting fewer asthma symptoms) in weeks in which children had a positive test for influenza, in those who had received the jab compared to those who did not. Two trials involved 1526 adults and 712 children who were given inactivated influenza vaccination, examined the harmful effects caused immediately after injection. These studies ruled out the likelihood of any more than four out of 100 people having a resultant asthma attack in the first two weeks after getting their flu jab. There was not enough information to compare different vaccination types.
We found four observational studies that examined this question. Overall, we found that, though data are sparse and not adequately statistically adjusted, ART and chemotherapy together compared to chemotherapy alone and ART and chemotherapy compared to ART alone increases the likelihood of KS remission and reduces the risk of death in HIV-infected children diagnosed with KS. The quality of this evidence is, however, weak. Future clinical trials of KS treatment options in HIV-infected children are needed.
Unfortunately we only found two randomised controlled trials that studied the use of art therapy for people with schizophrenia. Both studies did not include enough participants to make the results meaningful and we were unable to draw clear conclusions regarding the benefits or harms of art therapy from these studies. More research is needed to determine the value of art therapy in this population.
In this review, we analysed data from four small trials of unclear quality. It was not possible to separate data of bulky early stage disease (stage IB2 and IIA lesions greater than 4 cm) from the overall results. We found limited evidence to suggest that the addition of cisplatin chemotherapy to radiotherapy prolongs survival (time to death) and delays progression of the cancer when given after surgery to women with cervical cancer stage IA2 to IIA with risk factors for recurrence. The combined therapy was associated with more severe side effects than radiotherapy alone. This evidence is limited by the small numbers and moderate quality methodological quality of included studies. ?We conclude that it seems appropriate to offer these women chemotherapy plus radiotherapy after surgery, however, more evidence regarding the relative benefits and risks is needed; this will hopefully be provided by the results of three ongoing trials.
The review of 17 trials (some funded by drug companies) found that the trials were not of high quality; however the evidence suggested that there are no clinically important differences between giving fluids orally or intravenously. For every 25 children treated with fluids given orally, one child would fail and require intravenous rehydration. Further, the results for low osmolarity solutions, the currently recommended treatment by the World Health Organization, showed a lower failure rate for oral rehydration that was not significantly different from that of intravenous rehydration. Oral rehydration should be the first line of treatment in children with mild to moderate dehydration with intravenous therapy being used if the oral route fails. The evidence showed that there may be a higher risk of paralytic ileus with oral rehydration while intravenous therapy carries the risk of phlebitis (ie inflammation of the veins).
After a wide search for studies, we identified four trials involving 139 participants in total that met our criteria for inclusion in the review. Three randomised controlled trials compared the three different non-antiepileptic drugs tizanidine, tocainide and pimozide with carbamazepine, which is the standard drug treatment. No new trials were identified for the update of this review in 2013. Tizanidine did not produce significantly more benefit than carbamazepine according to low-quality evidence. The reporting of the tocainide trial did not allow us to assess whether the drug helped the pain of trigeminal neuralgia, but studies that were not part of this review suggest that this treatment can have serious harmful effects on the blood. Side effects of pimozide were very common but there was low-quality evidence that it was more effective than carbamazepine. In a fourth trial there was low-quality evidence that proparacaine hydrochloride eye drops did not show any significant benefit. There is insufficient evidence from randomised controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. Further well-designed randomised controlled trials are needed to establish whether non-antiepileptic drugs are beneficial in trigeminal neuralgia. The searches for the review are up to date to May 2013.
This overview drew together and summarised evidence from 13 systematic reviews that contained 17 relevant randomised controlled trials (the best type of study for this type of question) published up to 2013. Collectively, these trials compared 10 different types of wound dressings against each other, making a total of 37 separate comparisons. The different ways in which dressing types were compared made it difficult to combine and analyse the results. Only four of the comparisons informed by direct data found evidence of a difference in ulcer healing between dressings, but these results were classed as low quality evidence. There was no clear evidence that any of the 'advanced' wound dressings types were any better than basic wound contact dressings for healing foot ulcers. The overview findings were restricted by the small amount of information available (a limited number of trials involving small numbers of participants). Until there is a clear answer about which type of dressing performs best for healing foot ulcers in people with diabetes, other factors, such as clinical management of the wound, cost, and patient preference and comfort, should influence the choice of dressing. This plain language summary is up-to-date as of April 2015.
Syphilis is a potentially fatal, sexually transmitted disease that passes from a pregnant woman to her unborn baby. If the woman is untreated, the fetus might be aborted or her baby may be born with the disease, suffer permanent disability and be disfigured. The effectiveness of penicillin in curing infection with syphilis in pregnant women and preventing the baby being born with congenital syphilis was established soon after its introduction in the 1940s and before the widespread use of randomised controlled trials. Although rare in developed countries, the incidence of syphilis is high and increasing in many developing countries, particularly where HIV/AIDS is common. The review of trials found no trials comparing the effectiveness of different doses of penicillin or comparing penicillin with other antibiotics. More research is needed to find the best dosage and duration of treatment.
Adults over 18 years of age, regardless of gender and ethnicity, with USN after stroke diagnosis measured by clinical examination or radiographically by computed tomography or magnetic resonance imaging, regardless of whether they were evaluated by any paper-and-pencil tests. We considered including people diagnosed with any type of stroke (ie, ischemic or hemorrhagic) from the acute phase (the first 24 to 72 hours) until one year after the stroke. We identified two studies involving 30 participants up to April 2015. We are uncertain as to whether comparison of different pharmacological interventions (rivastigmine, transdermal nicotine)showed an important effect on (1) the ability of people to recognize their paralyzed limb, and (2) independence in daily life functions after stroke, because results were imprecise and included studies did not report most of the predefined outcomes (ie, falls, balance, depression or anxiety, poststroke fatigue, and quality of life). We considered the quality of included studies to be reasonable. Given the small sample size and methodological limitations (participants were assigned in a successive manner in one study), no conclusions can be drawn regarding the effectiveness of pharmacological medications in USN after stroke. The quality of the evidence obtained from available randomized controlled trials was very low. The effectiveness and safety of pharmacological interventions for USN after stroke are therefore uncertain. Additional large randomized controlled trials are needed to evaluate these treatments.
This review of 35 randomised controlled trials found that laparoscopic surgery is feasible and less expensive than open surgery in the treatment of tubal ectopic pregnancy. In selected patients, non-surgical treatment options can be used. Medical treatment with systemic methotrexate is an option for women with tubal ectopic pregnancy with no signs of bleeding whose pregnancy hormone blood levels are relatively low. An evaluation of expectant management of tubal ectopic pregnancy cannot be adequately made yet.
The review authors searched the medical literature to identify studies that compared protein intake as follows: between 3 and 4 g of protein per kg of infant body weight each day versus less than 3.0 g/kg/d or greater than 4.0 g/kg/d by low birth weight infants fed formula during their initial hospital stay. Increased protein intake resulted in greater weight gain of around 2.0 g/kg/d. Based on increased body incorporation of nitrogen, this was associated with increased lean body mass. The present conclusion was based on six studies that changed only the protein content of the formula and was supported by three additional studies that made changes in other nutrients as well. No significant difference in the concentration of plasma phenylalanine was noted between infants fed high or low protein content formula. The review was limited in the conclusions made because differences in protein content among comparison groups in some of the individual trials were small and formulas differed substantially across studies; some studies included healthier and more mature premature infants. Study periods varied from eight days to two years, so information on long-term outcomes was limited. Existing research is not adequate to allow specific recommendations regarding formula with protein content that provides more than 4.0 g/kg/d.
The aim of this study was to investigate the efficacy and safety of valerian for anxiety disorders. Only one study was identified, involving 36 patients and comparing valerian with placebo and diazepam. This study found no significant differences in effectiveness between valerian and placebo, or between valerian and diazepam, for clinician-rated anxiety symptoms, and that both valerian and diazepam were equally well tolerated by patients. However, additional studies with larger numbers of patients are necessary before drawing conclusions about the effectiveness and safety of valerian as a treatment option for anxiety disorders.
The main limitation of our updated review was that bleeding following tonsillectomy is an uncommon event (occurring in 3% to 5% of children). We found all the data from randomized controlled trials that are currently available (15 trials studying approximately 1000 children). Our results were consistent with both an increased and decreased risk of bleeding. There were insufficient data to compare the risk of bleeding with each individual type of NSAID. However, we were able to compare ketorolac, which has been perceived as having a greater risk of bleeding, with the other NSAIDs and found no increased risk of bleeding. There was less nausea and vomiting when NSAIDs were used as part of the pain relief regime than when NSAIDs were not used. There is insufficient evidence to exclude an increased risk of bleeding when NSAIDs are used in paediatric tonsillectomy. They do, however, confer the benefit of a reduction in vomiting.
There are only a few good quality studies comparing the acute treatment of early episode schizophrenia with an antipsychotic medication compared to placebo or psychosocial treatment. It appears that initial medication treatment reduces the study attrition rates while also increasing the risk for medication-induced side effects. Data are too limited to assess the effects of initial antipsychotic medication treatment on outcomes for individuals with an early episode of schizophrenia.
We included randomised studies comparing people receiving flu vaccine with those receiving no vaccine (placebo or no treatment). For this review update, we found eight trials studying 12,029 participants. Four of these studies examined patients with known heart disease (1682 participants), and the other four focused on the general population or elderly people (10,347 participants). The general population studies reported cardiovascular disease outcomes as part of their safety analyses, but the numbers of cases were too few to allow a judgement on whether flu vaccination was protective in these populations, and no differences were seen between groups. Overall, studies in people with heart disease suggest that flu vaccination may reduce death as a result of cardiovascular disease and may reduce combined cardiovascular disease events (such as heart attacks, strokes, necessity for bypass operations, etc.). However, these studies were small and had some risk of bias, so larger studies of better quality are needed to confirm the results.
In this review of 21 relevant randomized controlled trials, most studies examined the effects of albendazole. In patients with viable lesions, there is only evidence available for adult patients; this suggests that albendazole may reduce the number of lesions. In patients with non-viable lesions, there is only evidence available for children; this suggests that seizure recurrence was lower with albendazole, which goes against the opinions of some experts. There is insufficient evidence available to assess praziquantel.
We performed a search which included studies up to 20 December 2017. We identified two randomised clinical trials (where participants are divided by chance into the trial groups) which met the requirements for our review and followed-up the participants for at least two years. We identified 19 further observational studies from which we were able to report some findings on harms in a narrative form. The randomised trials included 107 infants who were given glucocorticosteroids and 104 who were given placebo. Trials were funded by charities, public organisations, and received support from private sector companies, all of which did not seem to have any interest in the outcome of the respective trials. Funding The included trials outlined their sources of funding, and the review authors deemed that there were no conflicts of interest. Review authors did not receive funding to carry out this review. Key results We did not find any differences between the groups of infants treated with glucocorticosteroids compared with placebo in terms of mortality, adverse events, ability to clear jaundice, or need for a liver transplant. Quality of the evidence We assessed the two trials as having low risk of bias (we had no concerns that their design and reporting may deviate from the truth), but they were at high risk of imprecision (inexact evaluations of outcomes). They used different categories for adverse events, and we were unable to combine the data from the trials. We could not include enough infants in our analyses (only two published trials) in order to detect small differences between the two intervention groups. The certainty of the evidence was low for mortality, adverse events, ability to clear jaundice, or need for a liver transplant outcomes. One further ongoing trial was identified, with no currently available results. Future steps We need further randomised clinical trials that compare glucocorticosteroids with placebo in order to find out if glucocorticosteroids are of benefit in the postoperative management of infants with biliary atresia. Such trials need to be conducted at different clinical centres.
We identified six studies involving 7999 people receiving treatment with methadone (7786 people) or buprenorphine–naloxone (213 people ) for opioid dependence. Four of the studies were randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups), while the other two studies followed groups of people over time. Four of the studies were funded by the National Institutes for Health Research and by the Health Research Board, with one study not reporting the funding source. One study was also funded by the drug company of buprenorphine–naloxone. At three or more months follow-up, this review found no evidence on benefit of the supervised dosing with respect to keep people in treatment, or reduce opioid use, mortality reduction and adverse drug events. One study found that supervised dosing led to a reduction of diversion. None of the studies assessed the effect of supervised dosing on pain symptoms, drug craving, days of unsanctioned opioid use, overdose and hospitalisation. We are unable to make any conclusion about the effectiveness of supervised dosing compared to dispensing of medication as take-home doses, in the context of OST. Further research is required to determine the effectiveness of supervised or take-home dosing in OST. Overall, the studies were moderately well-conducted, but there was a small number of studies reporting outcomes of interest, therefore insufficient to evaluate the efficacy of intervention such as diversion, opoid use reduction, retention in treatment and frequency of unsanctioned opioid use, Furthermore, low rates of occurrence of some events between studies resulted in the overall quality of the evidence being assessed as low and very low. This indicates that further evidence would be likely to change the estimates of relative effect made in this review.
The evidence in this review, carried out by authors from Cochrane Oral Health, is up to date as of 12 November 2018. Eight studies, with over 700 participants, were included. Two studies were conducted in the USA, two in Thailand, two in Germany and one each in Saudi Arabia and Turkey. The studies compared the use of liners under tooth-colored resin fillings (RBC) in permanent teeth at the back of the mouth to no liners for Class I and Class II fillings. One of the two studies in the USA took place in dental practices, the others in university-based dental schools. All participants were over 15 years of age. Very little evidence was found to show that a liner under Class I and II RBC fillings in permanent teeth in the back of the mouth reduced sensitivity in adults or children 15 years or older. No evidence was found to show that there was any difference in the length of time fillings lasted when placed with or without a cavity liner. No adverse events were reported in any of the included studies. The body of evidence identified in this review does not allow for robust conclusions about the effects of dental cavity liners. The quality of the evidence identified in this review is low and there is a lack of confidence in the effect estimates. Furthermore, no evidence was found to demonstrate a difference in how long restorations last when placed with or without dental cavity liners.
We searched the scientific literature for studies of anticoagulants in people with cancer. The evidence is current to December 2017. We included seven trials including 1486 participants with cancer. Most trials included participants with various types of cancer especially lung and pancreatic cancer. We found six studies using warfarin and one study using apixaban. When considering people with cancer in general, warfarin had no effect on mortality (death rate) or the risk of blood clots. However, it increased the risk of major bleeding in 107 more people per 1000 population and minor bleeding in 167 more people per 1000 population. Apixaban had no effect on mortality, recurrence of blood clots in blood vessels, major bleeding or minor bleeding; however, these findings were based on only one study. When comparing warfarin to no warfarin, we judged the certainty of the evidence (how sure and confident we are of the findings) to be moderate for mortality at one year and major and minor bleeding, low for symptomatic deep vein thrombosis (blood clot within a deep vein, most commonly the legs) and very low for pulmonary embolism (blood clot in the blood vessels of the lungs). When comparing apixaban to no apixaban, we judged the certainty of evidence to be low for mortality at three months, major and minor bleeding, pulmonary embolism and symptomatic deep vein thrombosis. Editorial note: this is a living systematic review. Living systematic reviews offer a new approach to review updating in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
On average, people taking eszopiclone fell asleep 12 minutes faster than those taking placebo, were 17 minutes less awake during the night and had, in total, about half an hour more sleep than people in the placebo group. As side effects, eszopiclone can cause unpleasant taste, dizziness, dry mouth, and tiredness during the day. Clinical studies did not find evidence that eszopiclone was causing serious harm or withdrawal symptoms or whether it was addictive if it was stopped and not taken after several weeks or months of treatment. Nevertheless, as clinical studies included in the review did not cover certain groups (e.g. elderly people with cognitive or motor problems or certain conditions of medication intake), it is important for patients to consult their doctor who knows their medical history and condition. Future research needs to compare eszopiclone with other sleep medications to help physicians and patients decide which of the available treatment options to prefer. In addition, sleep medications that are also well tolerated by elderly individuals and individuals with alcohol or drug problems need to be identified.
We included seven studies involving a total of 1529 children (780 with pneumonia (4 studies) and 749 with severe or very severe pneumonia (3 studies)) aged under 5 years from low-income countries. In four studies, a single large dose of vitamin D was used either when the child joined the study or within 24 hours of admission to hospital; in two studies, vitamin D was used for five days; and in one study, vitamin D was used for two days. One study excluded children whose vitamin D levels were normal. One study reported the cause of children's pneumonia. One study was funded by the New Zealand Aid Corporation; one was funded by an institutional grant; and five studies were unfunded. We are uncertain as to whether vitamin D has an important effect on outcomes due to the very-low quality of the evidence. Vitamin D may slightly decrease the time taken to get better from acute pneumonia (by 60 minutes) and the risk of death, and Vitamin D may increase the length of time in hospital (by 30 minutes) and the time taken for fever to resolve (by 90 minutes). However, there was no significant difference between groups for these outcomes. No major adverse events were reported. The quality of the evidence was very low, except for time to resolution of acute illness, which we assessed as low quality. We identified problems with the study methods and reporting, resulting in lack of precision in the included studies.
The review looked at trials that compared preterm babies who received steroids by inhalation to those who received steroids systemically (through a vein or orally) while they were receiving mechanical ventilation. We included two trials that involved 294 infants. One study included 278 infants and the other study included 16 infants. No new studies were included for the 2017 update. Both studies received grant support and the industry provided aero chambers and metered dose inhalers of budesonide and placebo for the larger study. No conflict of interest was identified. There was no evidence that inhaling steroids compared to systemic steroids prevented the primary outcome of death or bronchopulmonary dysplasia. The number of days the baby needed mechanical ventilation support or additional oxygen were increased in infants who received inhaled steroids versus infants who received systemic steroids. These outcomes were reported in both the trials. The rate of patent ductus arteriosus (failure for the ductus arteriosus, an arterial shunt in fetal life, to close after birth) was increased in the group receiving inhaled steroids. There was a lower incidence of high blood sugars in the inhaled steroid group compared with the systemic steroid group. These secondary outcomes were reported in only one trial (the larger trial). In a sub-sample of 52 children at age 7 years there were no differences in long-term follow-up outcomes between the inhaled and the systemic steroid groups. in an even smaller sample of 48 infants the outcome of 'ever diagnosed as asthmatic by seven years of age' was significantly lower in the inhaled steroid group compared with the systemic steroid group. According to GRADE the quality of the evidence was moderate to low.
We could not tell whether people taking LAMA were more or less likely to need oral corticosteroids for an asthma attack than people taking LABA because not many people needed them and the studies showed different results; overall three more people in 1000 might have an asthma attack on LAMA, but the real result could be anywhere between 29 fewer and 61 more than if you took a LABA. Similarly, too few people in the studies had serious side effects or asthma attacks that required urgent medical treatment to judge whether one treatment was better than the other. The studies showed that LAMAs might be a bit better than LABA for lung function (how well your lungs work), and LABAs slightly better for quality of life, but the differences were small and we could not tell if one was better than the other for most outcomes. The results were mostly based on four good studies of around 2000 people, which were between 14 and 24 weeks of duration. All of the studies looked at a LAMA drug called tiotropium.
This is an update of our review evaluating creatine treatment in muscle disorders that was first published in 2007. At this update we identified no new studies but we had previously found 14 randomised controlled trials with 364 participants which met our defined selection criteria. The methodological quality of these studies was high, with only one exception. Analysis of pooled results showed a significant increase in muscle strength in muscular dystrophies and an improvement in activities of daily living in muscular dystrophies and inflammatory myopathies during creatine treatment compared to placebo. Significant adverse events occurred only in people with glycogen storage disease type V presenting as an increase in muscle pain episodes and impairment in activities of daily living.
This review found that programmes to promote smoke alarms increased smoke alarm ownership and function modestly, if at all, and have not demonstrated a beneficial effect on fires or fire-related injuries. Counselling by health care workers, as part of child health care, may increase ownership and use of smoke alarms in homes but effects on injuries have not been examined. There is little evidence to support community-wide mass media or educational programmes or programmes to give away free smoke alarms as effective methods to promote smoke alarms or reduce injuries from fire. More research is needed to examine community-wide smoke alarm installation programmes.
We searched for all relevant studies up to 30 June 2017. We identified six clinical studies involving a total of 521 participants. All six studies compared drain use versus no drain use in individuals having an emergency open appendectomy for complicated appendicitis. Studies were conducted in the USA, India, Kenya, Pakistan, and Turkey. The age of the individuals in the trials ranged from 0 years to 82 years. The analyses were unable to show a difference in the number of individuals with intra-peritoneal abscess or wound infection when comparing drain use with no drain use. The death rate was higher in the drainage group than in the no drainage group. The hospital stay was longer (about two days - an 43.5% increase on an 'average' stay) in the drain group than in the no drain group. None of the studies reported the costs, pain, and quality of life. Overall, there is no evidence for any clinical improvement by using abdominal drainage in individuals undergoing open appendectomy for complicated appendicitis. All of the included studies had shortcomings in terms of methodological quality or reporting of outcomes. Overall, the quality of the current evidence is judged to be very low.
Six randomised controlled trials (484 patients) met our inclusion criteria. Five studies compared high volume PD with daily haemodialysis, extended daily haemodialysis, or continuous renal replacement therapy, and one study compared different intensities of PD on AKI patients. Compared to extracorporeal therapy, PD probably made little or no difference to death due to any cause or recovery of kidney function. PD probably slightly reduces the amount of fluid removal compared to extracorporeal therapy, and probably made little or no difference to infectious complications. It is uncertain whether PD compared to extracorporeal therapy has any effects on weekly delivered Kt/V, correction of acidosis, or duration of dialysis. One study (61 participants) reported little or no difference to death due to any cause, kidney function recovery, or infection between low and high and intensity PD. Weekly delivered Kt/V and fluid removal was lower with low compared to high intensity PD. There is currently not enough evidence to determine whether there are significant differences in death due to any cause or recovery of kidney function between patients treated with PD, extracorporeal therapies, or intensity of PD.
This review included one trial (22 participants), which compared the effect of three months' intravenous immunoglobulin (IVIg) therapy with placebo. Three participants were also treated with prednisone during the trial. Some limitations in the design, conduct, and reporting of the study might have affected the results. We were most interested in the degree to which treatment affected weight, in terms of either halting weight loss or producing weight gain. We identified only one randomised controlled trial of intervention for managing dysphagia in one muscle disease, inclusion body myositis. There was not enough evidence for or against any specific intervention for dysphagia. Clinically relevant effects of IVIg for dysphagia in inclusion body myositis can neither be confirmed nor ruled out using the evidence in this review. This trial did not assess weight gain or maintenance or fully report effects of IVIg on swallowing, which the investigators measured using a self report questionnaire and videofluoroscopy (a moving X-ray of swallowing). Any harmful effects were not fully reported. Overall quality of the evidence was low due to limitations in study design and reporting. The evidence is up to date to January 2016.
This review of three trials (1671 participants) found that routine administration of oxytocin with the anterior shoulder compared with use of oxytocin after delivery of the placenta did not have any influence on the amount of bleeding postpartum or retained placenta. The route of administration of oxytocin in two of the three included studies was through intravenous infusion. Cord management at delivery was consistent with double clamping and immediate cutting after delivery of the baby. Application of controlled cord traction was slightly different among the included studies. In two of the studies, the placenta was delivered with controlled cord traction when signs of placental separation were present. Fundal pressure on the uterus was used in one study from the beginning to ensure continued uterine contraction. Oxytocin was the only uterotonic assessed. There were no assessments of any impact on neonatal health. More well designed studies using consistent approaches in this area of the management of the third stage of labour are required.
This review analysed 10 studies (894 participants) and found evidence (combined odds ratio was 1.47 (95% CI 1.05 to 2.05) to suggest an increase in pregnancy rates after varicocele treatment compared to no treatment in subfertile couples, in whom, apart from poor sperm quality, varicocele in the man was the only abnormal finding. This means that 17 men would need to be treated to achieve one additional pregnancy. However, findings were inconclusive as the quality of the available evidence was very low and more research is needed with live birth or pregnancy rate as the primary outcome.
We examined the research published up to 22 November 2016. We found 8 clinical trials recruiting 637 babies up to 6 months of age who presented with symptoms of GOR. The recruited babies were mainly 'healthy' term babies (i.e. babies born within three weeks of the due date) who were bottle feeding. Three of the studies were funded by a pharmaceutical company, hence the quality of the evidence presented must be interpreted with caution. We found that term babies with GOR given feed thickeners had nearly two fewer reflux episodes per day. Babies with GOR were also 2.5 times more likely to have no reflux symptoms if feed thickeners were used. No studies reported information on failure to thrive (i.e. poor growth). We found that babies with GOR given feed thickeners showed an improvement in an important measure of acid reflux obtained from pH study. Reflux index (i.e. percentage of time of acidic reflux of pH < 4) was 5% lower in babies given feed thickeners. No major harms were reported in the eight studies. Due to study design limitations, we are moderately confident in the evidence for the reduction of two reflux episodes per day. Hence, feed thickeners can be useful in term babies who are bottle feeding and have troublesome GOR. We rated the quality of the evidence for the other outcomes as low due to the small number of studies with small numbers of babies recruited. Further research is needed to determine which type of feed thickener is better and whether feed thickeners are useful in babies with GOR who are breastfeeding or preterm.
This review included four studies (602 participants) that have looked at the results of surgery compared with non-surgical treatment for people who have had a heel fracture. The strongest evidence comes from one large multi-centre Canadian trial that recruited 424 participants. The remaining studies were small. All four studies had weaknesses in their design, conduct and reporting. Based mainly on the results from the largest study, the review found no strong evidence of differences between surgical and non-surgical treatment in functional ability, including walking, and quality of life, at three years after treatment. From two small studies, there is some evidence that participants having surgery were more likely to return to work more quickly. However, those having surgery were more likely to have a major complication such as surgical site infection after treatment. Conversely, those having surgery were less likely to have joint fusion surgery because they had developed arthritis later on. The review concluded that there was currently insufficient evidence to say whether surgical or non-surgical treatment of heel fractures is best. Further good quality research is recommended.
The aim of this review was to compare the response to inhaled beta-2 agonists delivered through a metered-dose inhaler (MDI) attached to home-made spacers, compared with beta-2 agonists delivered through a MDI attached to commercially produced spacers in children with acute exacerbations of wheezing or asthma. Six randomized clinical trials (RCTs) with 658 participants met the inclusion criteria of the review. Overall, this review fails to identify a difference between these two delivery methods for delivering bronchodilator therapy to children with acute asthma or lower airways obstruction attacks. However, given the small total sample and wide confidence intervals, equivalence between the treatments cannot be claimed.
• We found low-certainty evidence that multiple session early psychological interventions may be more effective than treatment as usual in preventing PTSD diagnosis three to six months after receiving the intervention. • We found very low-certainty evidence that multiple session early psychological interventions may be neither more nor less effective than treatment as usual in preventing PTSD, either immediately after, or at seven to 12 months after, the intervention. We also found very low-certainty evidence that multiple session early psychological interventions may be neither more nor less effective than treatment as usual in reducing the severity of PTSD symptoms, either immediately or at subsequent points of follow-up. • We found low-certainty evidence that multiple session early psychological interventions may be associated with a higher dropout rate than other psychological interventions. • We found low-certainty evidence that multiple session early psychological interventions may be neither more nor less effective than other psychological interventions in diagnosing PTSD; reducing the severity of PTSD, depression and anxiety; or in maintaining the general functioning of participants receiving the intervention. • We found no studies that measured adverse effects. • We found no studies that measured use of health-related resources. The current evidence base is small. However, new studies are being conducted and future updates of this review will incorporate the results of these.
Cervical dilatation and uterine interventions (such as hysteroscopy, endometrial biopsies, fractional curettage, and suction terminations) can be performed without any analgesia or anaesthesia; with regional anaesthetic injections as with paracervical block; using oral or intravenous analgesics and sedatives; or under general anaesthesia. Many gynaecologists use paracervical block for uterine intervention but it is unclear how effective and safe this method is. We included nine new studies in this updated review with a total of 26 studies involving 2790 women undergoing uterine interventions. The women were randomly allocated to paracervical block or an alternative. We found that, statistically, women had significantly less pain during cervical dilatation and uterine intervention with paracervical block than with placebo injection (saline or water) but clinically this difference may be unimportant. Paracervical block had no effect in five uncontrolled studies. There was no evidence that paracervical block reduced pain compared to alternative regional anaesthetic methods or systemic analgesics and sedatives. There was little information on important side effects. After updating, this review found that no local anaesthetic technique prevented pain as well as one would expect from general anaesthesia.
The evidence in this review is current to April 2015. We included 54 studies involving 2729 participants. All studies evaluated reproductive-aged women who were undertaking diagnostic surgery to investigate symptoms of endometriosis or for other indications. Twenty-six studies evaluated the role of 22 different biomarkers in diagnosing endometriosis, and 31 studies identified 77 additional biomarkers that had no value in differentiating between women with and without the disease. Only two of the assessed biomarkers, a neural fibre marker PGP 9.5 and hormonal marker CYP19, were assessed in sufficient number of studies to obtain meaningful results. PGP 9.5 identified endometriosis with enough accuracy to replace surgical diagnosis. Several additional biomarkers (endometrial proteome, 17βHSD2, IL-1R2, caldesmon and other neural markers) show promise in detecting endometriosis, but there are too few studies to be sure of their diagnostic value. The studies differed in how they were conducted, which groups of women were studied and how the surgery was undertaken. The reports were of low methodological quality, which is why readers cannot consider these results to be reliable unless confirmed in large, high quality studies. Overall, there is not enough evidence to recommend any endometrial test for use in clinical practice for the diagnosis of endometriosis. Further high quality research is necessary to accurately evaluate the diagnostic potential of the endometrial biomarkers for the diagnosis of endometriosis.
A wide variety of surfactant products have been formulated and studied in clinical trials. These include synthetic surfactants and animal derived surfactant extracts. Animal derived surfactant extracts are obtained from animal or human sources. Trials of surfactant replacement have either tried to prevent the development of respiratory distress in high-risk premature infants or treat established respiratory distress in premature infants. Infants with established respiratory distress syndrome who receive animal derived surfactant extract treatment have a decreased risk of lung rupture (pneumothorax), a decreased risk of lung injury (pulmonary interstitial emphysema), a decreased risk of dying, and a decreased risk of chronic lung injury (bronchopulmonary dysplasia) or death.
We searched for studies which compared different vaccines or compared vaccination to placebo. We were able to include four studies with 179 people in the review. Most (143) were under 16 years old. No study compared one vaccine to placebo. There were a high number of drop outs in two of the studies. Vaccination does result in an immune system response to the types of influenza used in the vaccine. However, this response may not result in protection against influenza infection or lung damage. There were a high number of adverse events, but none were serious or persistent. There is no evidence to show if regular influenza vaccine benefits people with cystic fibrosis.
We found that multimedia education programs about medications are superior to no education or education provided as part of usual clinical care in improving patient knowledge. There was wide variability in the results from the six studies that compared multimedia education to usual care or no education. However, all but one of the six studies favoured multimedia education. We also found that multimedia education is superior to usual care or no education in improving skill levels. The review also suggested that multimedia was at least as effective as other forms of education, including written education or brief education from a health provider. However, these findings were based on a small number of studies, many of which were of low quality. Multimedia education did not improve compliance with medications (i.e. the degree to which a patient correctly follows advice about his or her medication) compared with usual care or no education. We could not determine the effect of multimedia education on other outcomes, such as patient satisfaction, self-efficacy (confidence in their ability to perform health-related tasks) and health outcomes. The review findings therefore suggests that multimedia education programs about medications could be used alongside usual care provided by health providers. There is not enough evidence to recommend it as a replacement for written education or education by a health professional. Multimedia education could be used instead of detailed education given by a health provider when it is not possible or practical for health professionals to provide this service. This review found that there were differences between the types of education provided to the control groups and what results were measured. This limited the ability to summarise results across studies, so most of the conclusions of this review were based on results from a small number of studies. More studies of multimedia educational programs are needed to make the results of this review more reliable.
We identified one study that included a limited number of patients comparing eculizumab with placebo. The study was published in 2006, and was conducted in the US, Canada, Europe, and Australia with 26 weeks of follow-up. No patients died during the performance of this single study. The study showed a moderate improvement in the quality of life in patients treated with eculizumab. In addition, eculizumab reduced fatigue and the number of patients that withdrew from the study for any reason. Eculizumab showed a higher proportion of patients with transfusion independence. There was no difference between eculizumab and placebo in terms of adverse events, probably due to the low rate of events observed during the study. The trial did not assess other relevant outcomes such as overall survival, transformation to myelodysplastic syndrome and acute myelogenous leukemia, or development or recurrence of aplastic anemia on treatment. The confidence in the results is moderate to low. The study had limitations in its design and execution, and was sponsored by the manufacturer of the drug that was assessed. Moreover, the limited number of patients included in the study led to imprecise results. Larger studies should provide more information about the effect of eculizumab in patients with paroxsymal nocturnal hemoglobinuria. This plain language summary is current as of May 2014.
The reviewers found three studies addressing this issue. A meta-analysis showed a trend towards a beneficial effect of long-term corticosteroids on accumulation of disability; however only two small studies contributed to this result. It was not possible to reliably comment on the effect of long-term corticosteroids on the frequency of relapses. Side effects were poorly documented. Therefore rigorous randomised controlled trials of this treatment are warranted.
The one study that met the criteria for this review randomised healthcare providers to either psychosocial assessment or routine care and involved a total of 273 women. The providers who assessed psychosocial factors were more likely than those giving routine care to identify psychosocial concerns and to rate the level of concern as high. They were also more likely to detect concerns about family violence. The trial did not look at the development of anxiety or depression in these women. Not all healthcare providers chose to take part in the trial and some dropped out, leaving only 48 of the original 185 approached. This could mean that providers who were less interested in this area of clinical practice did not participate and bias the findings toward better than average detection of psychosocial risk. Two studies are currently in progress looking at the impact of early postnatal psychosocial assessment on the prevalence of antenatal and postnatal anxiety and depression.
We looked at all the published scientific literature and found 18 trials, involving a total of 6407 participants, that were of sufficient quality to include in this review. Eight trials tested the effect of duloxetine on painful diabetic neuropathy and six on the pain of fibromyalgia. Three trials treated painful physical symptoms associated with depression and one small study investigated duloxetine for the pain from strokes or diseases of the spinal cord (central pain). The usual dose of duloxetine is 60 mg. At this dose, there was moderate quality evidence that duloxetine reduced pain in both painful diabetic peripheral neuropathy and fibromyalgia. In diabetic peripheral neuropathic pain, a 50% or better improvement with duloxetine 60 mg per day was just over one and a half times more likely than with placebo. Another way of saying this is that five people with painful diabetic peripheral neuropathy had to receive duloxetine to achieve a 50% or better response in one person. The effect on fibromyalgia was similar but the number needed to treat for one person to improve by 50% or more was eight. On the basis of a single study it is not possible to determine if a dose of 20 mg is effective, and 120 mg was no more effective than 60 mg. We calculated that for diabetic neuropathy there have been enough trials to draw these conclusions and no more trials are needed. In fibromyalgia and the painful symptoms associated with depression, more trials are required to make convincing statements about the effectiveness of duloxetine. Most people taking duloxetine will have at least one side effect. These are mostly minor and the most common are feeling sick, being too awake or too sleepy, headache, dry mouth, constipation or dizziness. About one in six people stop duloxetine because of side effects. Serious problems caused by duloxetine are very rare. Although duloxetine is beneficial in the treatment of neuropathic pain and fibromyalgia there is little evidence from trials comparing duloxetine to other antidepressant drugs as to which is better. We have concluded that duloxetine is useful for treating pain caused by diabetic neuropathy and probably fibromyalgia. The information in this review is up to date to November 2013, the most recent search of the literature.
We found 11 trials (1537 participants in the relevant arms for this review) that met the criteria for our review. People with a poor prognosis generally were not eligible for entry into the randomised trials based on their poor level of health. There was an overall survival benefit for HGG participants receiving postoperative conventional radiotherapy compared to the participants receiving supportive care after surgery. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma. There were no clear differences in side effects (adverse effects) between these different treatment groups. There was insufficient data regarding other outcomes, namely progression-free survival and quality of life between these different treatment groups. There is insufficient data regarding the outcomes of survival, adverse effects, progression free survival and quality of life for hyperfractionation versus conventionally fractionated radiation and for accelerated radiation versus conventionally fractionated radiation. The quality of the evidence ranged from very low to high. Some of the trials were at a higher risk of bias due to missing details regarding how they divided participants into treatment groups, how many patients were lost to follow-up and possible selective reporting of outcomes such as adverse effects. Only 5 out of the 11 included trials were published after the year 2000. The majority of the trials included in the meta-analysis were published before 2000 and are now out of date. These older trials did not distinguish between the various subtypes of HGG, and they used outdated radiotherapy techniques such as whole brain radiotherapy rather than local radiotherapy (targeted only to the tumour and not the whole brain). Postoperative conventional daily radiotherapy improves survival for adults with good functional well-being and HGG compared to no postoperative radiotherapy. Hypofractionated radiation therapy has similar efficacy for survival as compared to conventional radiotherapy, particularly for individuals aged 60 and older with glioblastoma.
Eight randomised controlled trials including 332 participants with CIDP were eligible for this review. These compared IVIg with placebo (dummy treatment), plasma exchange, or steroid drugs. We found five randomised trials which together prove that IVIg improves disability more than placebo (dummy treatment). The results showed that three people would need to be treated for one person to improve. In the three trials that compared IVIg with other treatments, results with IVIg were similar to plasma exchange, oral prednisolone or intravenous methylprednisolone. The evidence was of moderate or high quality. In this review, there were mild and short-term side effects in around half of those who received IVIg. Six per cent of those treated with IVIg had serious side effects, which is a similar rate as with plasma exchange or corticosteroids. Each trial defined improvement in its own way and the trials used different measurement scales, so it is difficult to relate them to changes in the clinical condition of people with CIDP. Only one of the studies that compared IVIg with placebo had a long-term follow-up. It suggested that IVIg improves disability more than placebo over 24 weeks and possibly 48 weeks. Further research is needed to compare the long-term benefits as well as side effects of IVIg with other treatments. The most recent search for studies was in December 2012 and we updated the review with the results of one additional trial.
One of the included studies found that a general examination did not reduce sick leave among light duty workers compared to no intervention. However, another study found that army recruits were more fit for duty 12 months after a health examination. Results were inconsistent in five studies that compared job-focused pre-employment examinations with no health examination or with a general health examination. Pre-employment examinations may also result in the rejection of a job applicant. In six studies the rates of rejecting job applicants because of health examinations increased, on average, from 2% to 35%, but not in one study. Two of the included 11 studies (including 2164 people) compared job applicants that were considered fit during the health examination to those who received particular recommendations to address health-related issues based on the health examination. Both studies reported no difference in musculoskeletal injury rates between groups during follow-up. This means that job applicants were able to take care of the health problems identified during their health examinations. We rated all studied comparisons providing very low quality evidence. Health examinations that focus on health risks of particular jobs may be effective. Adequately dealing with potential health risks by changing work tasks or physical fitness training may also be effective. We need more and better quality evaluation studies. Not allowing people to work in certain jobs may have effects on their health. It also costs them money. Future research should assess both.
Only one study, involving 21 participants, was included in this review. The study compared PRT and bone graft versus bone graft alone (control) in patients with osteoarthritis of the knee who had surgery where a wedge of bone was cut (osteotomy) from their tibia (shin bone) in order to change the pattern of weight bearing on the knee. As in a fracture, the time for the bone to heal is an important factor in determining recovery after an osteotomy. The study found no difference between the PRT and control groups in patient-reported or clinician-assessed functional outcomes at one year. However, based on radiographic (x-ray) measures of bone healing, the study found a higher proportion of bones had healed by one year in those participants who had completed the study. One adverse event was reported in a participant receiving platelet-rich therapy From the limited evidence that is currently available, the review found that PRT had no effect on functional outcomes. PRT may be beneficial in accelerating and improving the incidence of union in osteotomies. The only complication reported was not necessarily related to the PRT treatment. No data were available regarding PRT in the treatment of acute fractures, non-united fractures or large bony defects. One other study involving hip fracture patients is currently underway, and will provide further evidence concerning the use of PRT in the future.
We found 7 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) comparing diet, physical activity, and behavioural (where habits are changed or improved) treatments (interventions) to a variety of control groups (who did not receive treatment) delivered to 923 overweight or obese preschool children up to the age of 6 years. We grouped the studies by the type of intervention. Our systematic review reported on the effects of multicomponent interventions and dietary interventions compared with no intervention, 'usual care', enhanced usual care, or some other therapy if it was also delivered in the intervention arm. The children in the included studies were monitored (called follow-up) for between six months and three years. Most studies reported the body mass index (BMI) z score: BMI is a measure of body fat and is calculated by dividing weight (in kilograms) by the square of the body height measured in metres (kg/m²). In children, BMI is often measured in a way that takes into account sex, weight, and height as children grow older (BMI z score). We summarised the results of 4 trials in 202 children reporting the BMI z score, which on average was 0.4 units lower in the multicomponent intervention groups compared with the control groups. Lower units indicate more weight loss. For example, a 5-year-old girl with a body height of 110 cm and a body weight of 32 kg has a BMI of 26.4 and a BMI z score of 2.99. If this girl loses 2 kg weight within a year (and gained 1 cm in height), she would have reduced her BMI z score by approx. 0.4 units (her BMI would be 24.3 and her BMI z score 2.58). Accordingly, the average change in weight in the multicomponent interventions was 2.8 kg lower than in the control groups. Other effects of the interventions, such as improvements in health-related quality of life or evaluation of the parent-child relationship, were less clear, and most studies did not measure adverse events. No study investigated death from any cause, morbidity, or socioeconomic effects. One study found that BMI z score reduction was greater at the end of both dairy-rich and energy-restricted dietary interventions compared with a healthy lifestyle education only. However, only the dairy-rich diet continued to show benefits two to three years later, whereas the energy-restricted diet group had a greater increase in BMI z score than the control group. This evidence is up to date as of March 2015. The overall quality of the evidence was low or very low, mainly because there were just a few studies per outcome measurement or the number of the included children was small. In addition, many children left the studies before they had finished.
Key results: The results of one of these trials indicate that patching therapy combined with any necessary glasses is more effective than glasses alone in the treatment of this condition. Two of the trials analysed the role of adding near activities to supplement patching therapy. These trials suggest there may be benefit to adding near activities to prescribed occlusion regime. No trial examining the role of optical penalisation (altering glasses strength) or using partial occlusion (frosted lens opposed to a patch) was found. The effectiveness of optical penalisation and partial occlusion for the treatment of strabismic amblyopia is unknown.  Quality of the evidence: The quality of the available evidence is high.
We included nine studies involving 210 ear, nose and throat residents and medical students. Four studies compared virtual reality endoscopic sinus surgery training with conventional training; one study compared virtual reality endoscopic dacryocystorhinostomy training versus textbook reading; two studies compared virtual reality temporal bone dissection training versus cadaveric temporal bone dissection training and two studies compared virtual reality temporal bone dissection training versus a small group tutorial with temporal bone models. None of the studies were funded by an agency with a commercial interest in the results of the studies. None of the studies evaluated whether training in virtual reality influences patient outcomes or non-technical skills. There is evidence to support the introduction of virtual reality into surgical training on the basis that the technical skills acquired by this method are as good as, or better than, those learnt through conventional training. Virtual reality can be added to the extensive range of activities that constitutes a comprehensive surgical training programme. Virtual reality simulation should also be considered as an additional learning tool for medical students. We assessed the quality of the evidence in this review for most outcomes as 'low' (using the GRADE system). The key reasons for this were issues related to study design. The evidence in this review is up to date to 27 July 2015.
This is an updated review, and we searched for new trials in July 2014. We included 13 small randomised clinical trials (RCTs), with a total of 479 participants. The trials assessed eight drugs: caffeine, sumatriptan, gabapentin, hydrocortisone, theophylline, adrenocorticotropic hormone, pregabalin and cosyntropin. Caffeine proved to be effective in decreasing the number of people with PDPH and those requiring extra drugs (2 or 3 in 10 with caffeine compared to 9 in 10 with placebo). Gabapentin, theophylline and hydrocortisone also proved to be effective, relieving pain better than placebo or conventional treatment alone. More people had better pain relief with theophylline (9 in 10 with theophylline compared to 4 in 10 with conventional treatment). No important side effects of these drugs were reported. The quality of the studies was difficult to assess due to the lack of information available. Conclusions should be interpreted with caution.
In medical literature searches complete to March 2016, we identified and included three clinical trials with 140 newborns comparing salbutamol with placebo. Two studies evaluated a single, nebulized (where the medicine is given in a fine mist) dose of salbutamol, and one study evaluated two different dosages. We found one additional trial that is still underway. Salbutamol reduced the duration of treatment with oxygen in newborns with transient tachypnea (reported in one study); whereas it did not affect the need for respiratory support or any other relevant outcomes. The results of this systematic review were consistent with either a benefit or a detrimental effect of salbutamol and did not provide a definitive answer to the review question.
We found 70 randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) comparing diet, physical activity, and behavioural (where habits are changed or improved) treatments to a variety of control groups delivered to 8461 overweight or obese children aged 6 to 11 years. We reported on the effects of 64 multicomponent interventions (different combinations of diet and physical activity and behaviour change), four physical activity interventions and two dietary interventions compared with no intervention, 'usual care’ or some other therapy if it was also delivered in the intervention arm. The children in the included studies were followed up between six months and three years. The average age of the children was 10 years. Most studies reported the body mass index (BMI) z score: BMI is a measure of body fat and is calculated by dividing weight (in kilograms) by the square of the body height measured in metres (kg/m²). In children, BMI is often measured in a way that takes into account sex and age, weight, and height changes as children grow older (BMI z score). We summarised the results of 37 trials in 4019 children reporting the BMI z score, which on average was 0.06 units lower in the intervention groups compared with the control groups. We summarised the results of 24 trials in 2785 children reporting BMI, which on average was 0.53 kg/m2 lower in the intervention groups compared with the control groups. We summarised the results of 17 trials in 1774 children reporting weight, which on average was 1.45 kg lower in the intervention groups compared with the control groups. Other effects of the interventions, such as improvements in health-related quality of life were less clear. No study investigated death from any cause, morbidity or socioeconomic effects. Serious adverse events were rare: only two of 31 trials with data reported any serious adverse events (4/2105 participants in the behaviour-changing intervention groups compared with 7/1991 participants in the comparator groups). This evidence is up to date as of July 2016. The overall quality of the evidence was low or very low, mainly because of limited confidence in how studies were performed, and the results were inconsistent between the studies. Also there were just a few studies for some outcomes, with small numbers of included children.
Twenty eight studies met our inclusion criteria. The majority of studies evaluated interventions designed to change health professional behaviour, for example, the distribution of educational materials, reminders to health professionals and patient education. For improving the use of imaging in osteoporosis, most interventions aimed at health professionals demonstrated benefit, and patient mediated, reminder, and organisational interventions appeared to have most potential for benefit. For low back pain studies, the most common intervention evaluated was distribution of educational materials and this showed varying effects. Other interventions in low back pain studies showed variable effects. For other musculoskeletal conditions, distribution of educational materials, educational meetings and audit and feedback were not shown to be effective for changing imaging ordering behaviour. Across all conditions, increasing the number of intervention components did not result in a larger effect of interventions.
We searched the databases until June 2013, and included 22 studies involving 1732 patients of whom 842 had an infraclavicular block and 930 had brachial plexus blockade with another technique. These other techniques were axillary block (injection in the armpit area; 14 studies), supraclavicular block (injection in the area just above the collarbone; six studies), mid-humeral block (injection in the upper arm; two studies) and parascalene block (injection in the lower neck area; one study). One study compared an infraclavicular block with both an axillary block and a supraclavicular block. The infraclavicular block had a high success rate and was as good as all other blocks in providing anaesthesia of the lower arm. Advantages of the infraclavicular block included a reduced risk of pain from the tourniquet applied to the upper arm during surgery and a faster performance time (four minutes on average) compared to more complex techniques of axillary or mid-humeral block that used three or four separate injections (instead of just one). Side-effects were uncommon, and no difference was seen between the infraclavicular block and all other blocks in this regard. In conclusion, this review showed that the infraclavicular block is an effective and safe choice for producing anaesthesia of the lower arm.
In July 2012 we searched medical databases for controlled trials of participants who had undergone aortic or arterial surgery and were randomly assigned to either statins or placebo (or standard care). Many vascular surgery patients are already taking statins; therefore we also included trials that randomly assigned participants to different doses of statin. Statin treatment should have been started any time between the decision to operate and performance of the operation and continued for at least 48 hours after the operation. We wanted to investigate the effect of this short-term statin therapy on the risk of death and cardiovascular events such as heart attack and stroke within 30 days of surgery. We also considered adverse effects of statins such as muscle pain. We found five studies that compared participants receiving statins with a control treatment or with placebo, but only three of these reported outcomes could be combined in the meta-analyses. These three studies were of high quality but studied only 178 participants in total. This means that evidence was insufficient to allow review authors to determine whether statins improved patient outcomes after surgery. We were also not able to establish whether any adverse effects such as muscle pain were associated with statin use. We found that two studies had compared different doses of atorvastatin, but evidence was insufficient to determine whether any benefits or risks were associated with using a higher dose. Given the limited quantity of data obtained from randomized controlled trials, further studies are required to allow investigators to gather better information about whether prescribing statins around the time of vascular surgery can improve outcomes. However, widespread use of statins in patients before they need surgery may make these studies impracticable.
We searched the available literature for trials in which people were invited either to collect specimens at home or to attend a clinic for collection of specimens. We found 10 relevant trials in total. Three trials (including 1566 people) provided data to assess the proportion of people who completed testing, diagnosis and treatment. All trials gave information about the percentages of people who took self-collected specimens for detection of chlamydia and gonorrhoea infections at home and those who took the test at a clinic. Nine studies reported percentages related to positive test results. Trials in this review were funded by governmental or non-governmental organisations. There was no evidence of a difference between home-based and clinic-based specimen collection in the proportion of people who completed testing, diagnosis and treatment. In the home-based group 45 infections were detected and treated in a total of 778 people invited to collect specimens at home. In the clinic-based group 51 infections were detected and treated in a total of 788 people invited to attend a clinic. We could not combine data from individual studies looking at the number of participants tested because the proportions varied widely. A lower number of participants diagnosed in the home-based compared with the clinic-based group was documented. The potential harms of testing with home-collected specimens were not evaluated in any trial. The GRADE quality for the main outcomes was moderate (index case management, positive test prevalence) or low (proportion of individuals tested). The quality of evidence was downgraded because of methodological limitations in the studies. Home-based specimen collection could result in similar levels of index case management forChlamydia trachomatisorNeisseria gonorrhoeaeinfection when compared with clinic-based specimen collection. The safety of home-based specimen collection compared with clinic-based specimen collection have not been evaluated.
We included all studies which have looked at drug treatment against placebo (sugar pill) or other kinds of mental health support. People included in the studies had an equal chance of receiving either treatment. Unfortunately, even though depression is very common and finding good treatments for depression are highly valued by patients on dialysis, there are only a few small studies to tell us about whether drug treatments are both safe and reduce symptoms. Based on this information, we still don't know whether depression treatment works well for people treated with dialysis and is safe (doesn't cause excess and serious side effects). The question of whether drugs can reduce symptoms of depression and improve quality of life for people on dialysis is still important. We need a big study that involves dialysis patients and assesses a commonly-used antidepressant drug with a placebo and measures the treatment effects based on what patients and their families value most.
We included 244 trials, with 28,619 participants. The included trials assessed the effects of different kinds of nutrition support (i.e. dietary advice, enriching regular food with extra protein and calories, protein shakes, feeding through a catheter directly into a vein or through a tube directly into the stomach or gut). The nutrition support was provided to people in the trial who were ill with many different types of diseases and undergoing different procedures. What they all had in common was that they were at risk by at least one measure, including the trialists' clinical opinion. We found no evidence of a difference between nutrition support and control for risk of death. We found that 8.3% people died at short-term follow-up in the control groups compared with 7.8% in those who had been given nutritional support (low quality of evidence). At the longest point of follow-up 13.2% people in the control groups died compared with 12.2% in those who had been given nutritional support (low quality of evidence). We found no evidence of a difference between nutrition support and control for risk of a serious complications in the short term. People in the control groups had a serious complication rate of 9.9% at short-term follow-up compared with 9.2% with nutrition (low quality of evidence). At long-term follow-up 15.2% of people in the control groups had a serious complication compared with 13.8% in the nutrition groups (low quality of evidence). These results are based on just over 21,000 participants. Nutrition may increase weight by about 1.32 kg compared with people in the control groups. The increase in weight of 1.32 kg on average is of uncertain benefit. We could not reliably assess the effects on quality of life due to the variation in the reporting of this information. When we looked at the different types of nutrition support, a secondary analysis suggested that tube-feeding might be beneficial, reducing serious complications at maximum follow-up, but the strength of this finding is low. The evidence for our conclusions is of low quality for death and serious complications, and very low quality for weight. All trials had a high risk of bias (i.e. the trials were all conducted in a way that may overestimate the benefits and underestimate the harms of nutrition support). The results were consistent for death and serious complications, but there was a high level of variation in the effects on weight across the studies.
This review confirms the greater response rates achievable by using purine antagonists but at the cost of greater toxicity, mainly infections. There is inconclusive evidence whether treatment with purine antagonists improves survival. None of the studies included quality of life data. More research is needed to fully explore the role of purine antagonists in the treatment of B-CLL and their potential impact on survival.
This review of clinical studies found that increasing haemoglobin to high levels lowered the chance of a person having a seizure, but increased blood pressure. Haemoglobin levels above 133 g/L did not reduce the risk of death in people with heart and kidney disease.
The evidence was current to March 2012. We analysed 17 comparisons of physical conditioning as part of a return to work strategy. Some trials examined physical conditioning in addition to care as usual versus care as usual only, and others compared physical conditioning to other types of interventions such as standard exercise therapy. Participants had either acute back pain (duration of symptoms less than six weeks), subacute back pain (duration of symptoms more than six but less than 12 weeks), or chronic back pain (duration of symptoms more than 12 weeks). Participants were followed for anywhere from three weeks to three years. We divided physical conditioning into light or intense, depending on its intensity and duration. Results showed that light physical conditioning has no effect on sickness absence duration for workers with subacute or chronic back pain. We found conflicting results for intense physical conditioning for workers with subacute back pain. Intense physical conditioning probably had a small effect on reducing sick leave at 12 months follow-up compared to usual care for workers with chronic back pain. Involving the workplace, or physical conditioning being part of integrated care management may have had a positive effect on reducing sick leave, but this needs further research. The quality of the evidence ranged from very low to moderate. Although 16 of the included studies were well designed and had no major flaws, some studies were poorly conducted and the small number of participants in most studies lowered the overall quality of the evidence.
Evidence is current to 27 March 2014. We found 23 relevant randomized controlled trials with 1250 participants undergoing cardioversion procedures. These studies compared one anaesthetic drug against one or more other drugs, including propofol, etomidate, thiopentone, sevoflurane, midazolam and diazepam. Study authors considered clinical outcomes such as decreased blood pressure, interrupted breathing and whether cardioversion was successful, as well as patient relevant outcomes such as recall, nausea and vomiting, pain on injection and satisfaction with the procedures. In addition to a variety of drug comparisons between studies, differences in study methods were described, with drugs given in different doses and over different lengths of time. These differences meant that it was inappropriate to combine the results of these studies. We believe that the quality of these studies was not sufficiently high, and that it would be misleading to combine the findings of all studies within this review. Study authors had not taken enough steps to reduce the risk of differences in methods within the studies, for example, by masking doctors and assessors regarding which drug was given to each patient. Most authors of individual studies concluded that all agents studied were adequate for making patients unaware during cardioversion. It is our opinion that at present, there is no evidence to suggest that drugs used by anaesthetists to make patients unaware of cardioversion should change.
The evidence is current to July 2014. We included in our analysis three multicenter randomized trials involving a total of 2303 participants. All three trials recruited participants aged 60 years or younger with a cryptogenic stroke or minor stroke and had a PFO diagnosed by specialist heart scan. 1150 participants were randomized to the TDC group where the procedure was performed with the Amplatzer device in two studies, and with the STARFlex device in one study. The mean follow-up period of all three included trials was less than five years. Two studies were sponsored by St Jude Medical and one study was sponsored by NMT Medical. We found that, when compared with medical therapy, TDC failed to show any significant benefit in reducing the risk of recurrent stroke or similar events. However, there was a possible protective effect on recurrent strokes in those participants for whom an Amplatzer device was used compared with medical therapy. We did not find evidence that TDC increased the rate of serious adverse events overall. However, TDC increased the risk of new-onset atrial fibrillation (where there is a problem with the rate or rhythm of the heartbeat) and may be associated with the type of device used. We performed this systematic review of three randomized trials to compare both the safety and efficacy of TDC with medical therapy on recurrent cerebrovascular events in people with cryptogenic stroke and PFO following theCochrane Handbook for Systematic Reviews of Interventions.The major problem in terms of risk of bias is the high dropout rate compared with event rate in these three trials and different dropout rates between groups. Meanwhile, we lack individual-level data for analysis. Although there is a suggestion of potential benefit with the Amplatzer device closure in preventing recurrent stroke, our findings still need to be confirmed in further studies.
We included 19 randomized controlled trials in the review, with a total of 1756 patients. The review of trials found that a dose of corticosteroid during tonsillectomy or adenotonsillectomy can prevent vomiting for one out of every five children who gets the drug. Children also return to a normal diet more quickly and they have less pain after surgery.
We conducted a search on 13 December 2017 and found just two UK studies that included 84 participants, comparing a self-management approach with normal care for adults with bronchiectasis. One study looked at the impact of an expert patient self-management programme and the other, involving just a small number of participants with bronchiectasis, looked at self-management in combination with exercises to improve lung function. Neither study included children. Health-related quality of life did not improve in either study. Although there were more deaths in the group receiving self-management in one study, the numbers were very small and we do not know whether the difference is meaningful. The number of admissions to hospital, and lung function showed no benefit from self-management. In one of the studies, people receiving self-management felt more empowered to manage their condition. There was no information on the impact of self-management on symptoms of bronchiectasis, adverse events or potential cost savings arising from more effective self-management. There are no studies looking at self-management in children. Overall there is not enough information to assess whether strategies to support self-management may help people with bronchiectasis and further studies are needed. Future studies will need to look at how often flare ups occur, how often antibiotics are prescribed, and how long for, whether people have a better quality of life, and the impact of self-management on costs of care. It is also important to look at self-management for bronchiectasis in children. This review is based on only two small trials and the quality of the studies is very poor. With only two studies looking at very specific approaches to self-management we cannot say with any degree of certainty whether self-management strategies work for people with bronchiectasis, but until further evidence is available we advocate adherence to current international guidelines that recommend self-management for people with bronchiectasis.
Twenty one good quality studies, enrolling 6016 participants, which used different classes of antimicrobials for treating acute cystitis in women for 3 up to 10 days, were included in this review. The classes of antimicrobials included in the review proved equally effective for the symptomatic cure. Fluoroquinolones proved more effective than beta-lactams for the short-term bacteriological cure, but the significance of this finding is doubtful. Fewer rashes developed in patients treated with fluoroquinolones. Nitrofurantoin caused fewer rashes than TMP-SMX while having similar rates of any adverse events. Given the small number of studies included in each comparison and for each outcome it is recommended that further randomised controlled trials be conducted.
In literature searches updated in April 2017, we found one randomised controlled trial (302 intubations) that met the inclusion criteria of this review. Rates of successful intubation at first attempt with or without use of a stylet as an aid were similar, at 57% and 53%, respectively. Success rates with and without use of a stylet did not differ between infants of different weights, or between trainee paediatric doctors with different levels of experience. The length of time it took to intubate and the number of attempts made before successful intubation were comparable between groups. The incidence of a drop in a patient’s oxygen level and in heart rate was equivalent between groups, as was the reported incidence of trauma to the airway associated with the procedure. The quality of evidence was low. We downgraded the level because we included only one unblinded study.
A total of 130 participants (all with low anaesthetic risk) were included in five trials which compared abdominal wall lift combined with very low pressure pneumoperitoneum and standard pneumoperitoneum. All five trials had a high risk of bias (introducing the possibility of overestimating benefits or underestimating the harms of abdominal wall lift). No-one died as a result of surgery. There was no significant difference in the rate of serious complications related to the surgery. None of the trials reported quality of life, the proportion of people discharged as laparoscopic cholecystectomy day-patients, or pain between four and eight hours after the operation. None required conversion of key-hole surgery to an open operation using a larger incision. There was no significant difference in the operating time between the two groups. Abdominal wall lift versus pneumoperitoneum  A total of 774 participants (the majority with low anaesthetic risk) who underwent planned laparoscopic cholecystectomy were included in 18 trials which compared abdominal wall lift and standard pneumoperitoneum. All the trials had a high risk of bias. No-one died as a result of the surgery. There was no significant difference in the rate of serious complications related to surgery. None of the trials reported quality of life or pain between four and eight hours after the operation. There was no significant difference in the rate of serious adverse events, the proportion of people who underwent an open operation using a larger incision, or the proportion discharged on the same day of surgery. The operating time was about seven minutes longer on average if the operation was performed using abdominal wall lift rather than pneumoperitoneum. In summary, abdominal wall lift does not seem to offer an advantage over pneumoperitoneum in any of the patient-oriented outcomes for laparoscopic cholecystectomy in people with low anaesthetic risk. Abdominal wall lift may increase costs by increasing the operating time. Hence it cannot be recommended routinely. The safety of abdominal wall lift is yet to be established. More randomised clinical trials on the topic are needed since the possibility of arriving at erroneous conclusions due to bias and due to the play of chance was high because of the design of the trials. Future trials should include people at high risk during anaesthesia. Furthermore, such trials should employ blinded assessments of outcome measures.
We found 13 studies involving 467 participants that tested different treatments for sensory loss. There is limited evidence that these treatments may be effective. No more than one study examined each particular intervention, frequently the studies were of poor quality and lacked sufficient information. Further research is needed before clear recommendations can be made.
However, our primary research for this review showed that there was no strong evidence concerning the effectiveness of TCMHs in stopping bleeding from haemorrhoids. The included studies were few and of low quality. Limited, weak evidence showed that some formulae, when including Radix Sanguisorbae, Radix Rehmanniae, Fructus Sophorae, etc., may alleviate some symptoms caused by haemorrhoids. These symptoms include hematochezia and congestive haemorrhoidal cushions, in the short term. Additional, standardised trials are needed for meta-analysis to draw a final conclusion.
We found two studies where people were randomly put into one of two or more treatment groups (called randomised controlled trials) which were sufficiently relevant to the review topic. Both studies, which involved 1167 participants altogether, were conducted in men undergoing radiotherapy for prostate cancer and evaluated a bisphosphonate medicine called zoledronic acid. These men also received hormone treatment for their condition as reduced bone mineral density (BMD; how many minerals are in the bones, which determines how solid and strong the bones are) is a known side effect of this treatment. Studies measured and reported outcomes differently and we were unable to pool their results (data); however, limited evidence suggested that zoledronic acid might improve BMD in this specific group (men with prostate cancer) who received both hormone treatment and radiotherapy. There were few fractures or avascular necrosis events in the studies, therefore, it is very uncertain whether zoledronic acid has an impact on these important outcomes. As the studies were not specifically designed to evaluate the effect of zoledronic acid on radiotherapy-related bone outcomes, and participants also received hormone treatment, it is very uncertain whether the evidence applies to people undergoing pelvic radiotherapy for other cancers and people not receiving adjuvant hormone treatment. Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty. There is insufficient evidence that zoledronic acid and other medicines prevent radiotherapy-induced bone complications. This review highlights the need for clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis.
This review looked at the effectiveness of calcitonin for controlling pain from bone metastases. However, only two studies were found with very low quality evidence to support the use of calcitonin for patients suffering from bone pain. We updated the review in 2015 and did not find any more studies. There were slightly more side effects for the patients given calcitonin. Unless new studies provide additional relevant information about this treatment, other therapeutic approaches should be considered.
We found 30 trials, with a total of 1569 participants, and the interventions included changes to ventilator type and settings, earplugs and eye masks, relaxation therapy, sleep-inducing music, massage, foot baths, aromatherapy, valerian acupressure, sound masking, and changing the visiting times of family members. We assessed the effects of these interventions on sleep outcomes (e.g., quality and amount of sleep), length of stay in the ICU, the occurrence of delirium, other adverse events, and death. Overall, the quality of the evidence for an effect of the interventions on any of the outcomes was low or very low. Normally, we would try to pool findings from similar trials of each intervention, but this was difficult because the design of the trials varied greatly. We were able to combine the results from three trials of earplugs and eye masks and found that their use increased the number of hours slept and prevented delirium in adults in the ICU. However, we cannot be certain about these findings because of problems with how the trials were carried out. There was also some low quality evidence from four studies that music may improve subjective sleep quality and quantity, but we could not pool the data. Similarly, a low number of studies found that relaxation techniques, foot massage, acupressure, nursing or social intervention, and sound masking can provide small improvements in participant-reported or nurse-assessed sleep quality and quantity, but the quality of the evidence was low. The effects of the interventions on objective sleep outcomes (e.g., sleep measured by a machine) varied: the majority of studies that looked at the use of earplugs and eye masks found no benefit, and although the results from six trials of ventilator modes suggested that certain ventilator settings might offer benefits over others, the results of the individual trials did not always agree with each other. Only one study measured length of stay in the ICU and found no significant effect of earplugs plus eye masks. None of the included studies looked at economic outcomes, risk of post-traumatic stress disorder, or deaths. The trials did not clearly report adverse effects, although there was very low quality evidence that ventilator mode might influence certain adverse effects that can happen when people are on a ventilator. In summary, further well-designed and conducted research is needed to strengthen the evidence for the use of these interventions for improving sleep in critically ill adults.
Authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 23 January 2014. It includes 56 studies published from 1964 to 2011 in which 5068 participants were randomised to receive either a powered toothbrush or a manual toothbrush. Majority of the studies included adults, and over 50% of the studies used a type of powered toothbrush that had a rotation oscillation mode of action (where the brush head rotates in one direction and then the other). The evidence produced shows benefits in using a powered toothbrush when compared with a manual toothbrush. There was an 11% reduction in plaque at one to three months of use, and a 21% reduction in plaque when assessed after three months of use. For gingivitis, there was a 6% reduction at one to three months of use and an 11% reduction when assessed after three months of use. The benefits of this for long-term dental health are unclear. Few studies reported on side effects; any reported side effects were localised and only temporary. The evidence relating to plaque and gingivitis was considered to be of moderate quality.
The review of trials found that medical methods for abortion in early pregnancy can be safe and effective, with the most evidence of effectiveness for a combination of mifepristone and misoprostol (a prostaglandin). Almost all of the trials were done in well-resourced hospitals where women returned for check-up.
Previous studies indicate that glatiramer acetate, a synthetic drug, is effective in animal models of MS, and shows some benefits in MS patients. The objective of this review was to assess the efficacy of glatiramer acetate in RRMS and PMS patients. Among the pertinent medical literature six studies met the criteria of the methodological quality necessary for their inclusion in this review. 540 RRMS patients and 1049 PMS patients contributed to this analysis. The data showed no beneficial effects on disease progression in both MS forms, a slight beneficial effect  in the reduction of risk of relapses in RRMS patients and no benefits in PMS patients. Adverse events such as flushing, chest tightness, sweating, palpitations, anxiety and  local injection-site reactions occurred quite frequently, but no major adverse effects were observed.
Studies investigating the effect of vitamin B6 in improving the behaviour of children with autism spectrum disorder have been reported for over three decades. The purpose of this review was to summarize those studies and analyse the effectiveness of vitamin B6 as an intervention. Only three studies met the inclusion criteria of this review and of these only one study reported adequate data for analysis. Results were inconclusive and sample sizes were small. Therefore the use of vitamin B6 for improving the behaviour of individuals with autism cannot currently be supported. Further research using larger, well-designed trials is needed.
The review of trials suggests that these interventions may have some benefit to the outcomes of preterm infants; however, there continues to be conflicting evidence among the multiple studies. Before a clear direction for practice can be supported, evidence demonstrating more consistent effects of developmental care interventions on important short- and long-term clinical outcomes is needed. The economic impact of the implementation and maintenance of developmental care practices should be considered by individual institutions.
This review aims to identify whether certain recruitment strategies can help to increase the number of smokers enrolling into quit services. It also aims to determine whether these recruitment strategies have any impact on people successfully quitting smoking at six months or longer. This review covers 19 studies, with almost 15,000 participants, but the significant differences across these studies meant that we were unable to draw conclusive answers to our research questions. Our findings do, however, suggest that the following elements could result more people joining quit smoking programmes: (1) recruitment strategies tailored to the individual; (2) proactive strategies; and (3) increased contact time with potential participants. This review also highlights the areas within this field that need more attention: identifying the elements of a recruitment strategy that are more likely to effectively engage smokers; whether or not elements of recruitment strategies have an impact on quit rates; and identifying those recruitment strategies (or different combinations of particular recruitment strategies with certain smoking cessation programmes) that work better for different population groups.
This review included five trials with 311 eyes (267 participants). These studies included 160 eyes which had trabeculectomy compared to 151 eyes that had non-penetrating glaucoma surgery, of which 101 eyes had deep sclerectomy and 50 eyes had viscocanalostomy. This review showed that trabeculectomy is better in terms of achieving total success (pressure controlled without eyedrops) than non-penetrating filtering procedures. Although when we looked at the outcome of partial success (pressure controlled with additional eyedrops) it was more imprecise and our results could not exclude one surgical approach being better than the other. However, the review noted that these studies had some limitations regarding their design and were too small to give definitive information on differences in complications following surgery. None of the studies measured quality of life.
In May 2012 we searched, in a wide-ranging way, for all the useful studies (randomised controlled trials, or RCTs) we could find which compared fluoxetine with any other antidepressant in treating people with depression. One hundred and seventy-one RCTs were included, with 24,868 people in the analyses. Combining the results from all the trials, fluoxetine was similarly effective, but better tolerated, than older generation (tricyclic) antidepressants. In comparison with other new generation antidepressants, important differences in efficacy and in tolerability were found between fluoxetine and some of the antidepressants, for example, fluoxetine was less effective than sertraline and mirtazapine but better tolerated than reboxetine. These differences might have a clinical impact in everyday practice. However, when interpreting these differences it is important to bear in mind that the studies were short in duration (eight weeks or less) and that the average size of each trial was small (each included around 100 people). Moreover, most of the included studies were sponsored by drug companies, which could potentially have led to an overestimation of treatment effect. As a consequence, it is difficult to draw clear, clinically meaningful conclusions. More reliable information is needed about the respective safety profiles of antidepressants.
This review searched the available evidence that was up to date at 22 February 2017. We found 15 relevant studies including 3760 participants with an average age of 25 years (range 3 to 101) where 48% were male. The follow-up period in the trials ranged from 6 to 36 months. Two of the 15 studies declared financial support from companies that made tooth-filling material. In addition, we found four ongoing studies. There is low-quality evidence to suggest that primary teeth treated with the ART approach using high viscosity glass ionomer cement may be more likely than those receiving conventional treatment with the same material to result in restoration failure. In the treatment of primary teeth, ART may reduce pain experience compared with conventional treatment. The evidence available for evaluating the differences between ART and conventional treatments using other restorative materials or in permanent teeth is very low quality so we cannot draw any conclusions. None of the included studies reported on negative side effects or costs. The available evidence is low- to very low-quality. It is likely that further high-quality research may change our findings. There are four ongoing studies that may provide more information in the future.
We developed a comprehensive search strategy of all relevant scientific databases to identify all clinical trials to answer this question. Participants had to have a baseline systolic blood pressure (the top number of a blood pressure reading) of at least 140 mmHg or a diastolic blood pressure (the bottom number of a blood pressure reading) of at least 90 mmHg, or both of these. We did not restrict participants by age, gender, baseline risk or any other medical conditions. We found 25 clinical trials that compared the blood pressure lowering effect of seven nonselective beta-blockers with placebo in 1264 people with high blood pressure. On average, nonselective beta-blockers lowered blood pressure by about 10 mmHg systolic and 7 mmHg diastolic, and reduced heart rate by 12 beats per minute. This estimate is likely greater than the true effect because of biases in the running and reporting of the trials. We did not find convincing evidence that higher doses of nonselective beta-blockers lowered blood pressure more than lower doses. However, higher doses of nonselective beta-blockers significantly lowered heart rate compared with lower doses, which could lead to more side effects. Since the blood pressure lowering effect for systolic is similar to the blood pressure lowering effect of diastolic, the effect of this subclass on pulse pressure (the difference between systolic and diastolic) was small at about 2 mmHg. The quality of the evidence is low due to the presence of extreme outliers and high risk of biases.
We identified seven clinical trials involving 895 people with one-sided mild, moderate or severe Bell's palsy of unknown cause. All of these trials reported rates of incomplete recovery (the proportion of people left with facial weakness) and we were able to combine the results. People in the studies were aged from 2 to 84 years. They were treated with corticosteroids or placebo (inactive treatment), either alone or in combination with other therapies. One trial only involved children, from 24 months to 74 months old. The duration of the included studies for adults and children ranged from 157 days to 12 months. Incomplete recovery According to moderate quality to high quality evidence, corticosteroids reduced the number of people left with facial weakness after Bell's palsy compared to placebo (a pretend medicine). This finding was based on data from seven studies involving 895 participants with Bell's palsy of varying degrees of severity. We calculated that to stop one person from being left with facial weakness, 10 people need to be treated. Five studies provided data on long-term after-effects of Bell's palsy following treatment. Two of the studies (75 participants) looked at persistent effects on facial appearance after six months or more. The effect was nearly the same for corticosteroids and placebo, showing that participants who had corticosteroids benefited slightly, although this evidence was low quality. Data from three studies (485 participants) showed clearly that people who received corticosteroids developed less motor synkinesis (unwanted facial movements) and crocodile tears (watery eyes when eating or chewing), compared with people who received placebo alone. This finding was based on moderate-quality evidence. Side effects Three studies reported that no side effects could be attributed to corticosteroid treatment. Based on moderate-quality evidence from three studies (715 participants), numbers experiencing side effects were similar with corticosteroids and placebo. The evidence is current to March 2016.
Through June 2015, we searched for trials of education about family planning after having a baby. We also wrote to researchers to find other trials. The trials had to study how much the program affected family planning use. The program must have occurred within a month after the birth. We entered the data into RevMan and used the odds ratio to examine effect. We also looked at the quality of the research methods. We found 12 trials with 4145 women. Eight studies were from the USA and the others were from Australia, Nepal, Pakistan, and Syria. Four trials provided one counseling session before hospital discharge. Of eight studies with more than one contact, five focused on teens. Three of the five had home visiting, one used clinic services, and one had personal and phone contacts. Of three studies with women and teens, two had home visits and one used phone contact. Six trials had results of moderate quality. In a study with adolescents, the group with home-based mentoring had fewer second births within two years compared to the control group. Of trials with lower quality evidence, two showed some effect. In Nepal, more of the women with some counseling right after delivery may use birth control at six months than those with a session later or none. In Australia, more teens in a special home-visiting program used birth control correctly at six months than those with standard home visits. We found moderate to low quality results overall. Most of those with some effect were low quality. Better program design and carrying out could make them stronger. Even still, some programs might cost too much for some settings.
We assessed the effect of cutting down the amount of saturated fat we eat on health outcomes including dying, heart disease, stroke and cancer for at least two years. We only looked at studies of adults (18 years or older). This included men and women with and without cardiovascular disease. We did not include studies of acutely ill people or pregnant or breastfeeding women. We found 15 studies with over 59,000 participants. The evidence is current to March 2014. The review found that cutting down on saturated fat led to a 17% reduction in the risk of cardiovascular disease (including heart disease and strokes), but no effects on the risk of dying. The review found no clear health benefits of replacing saturated fats with starchy foods or protein. Changing the type of fat we eat, replacing saturated fats with polyunsaturated fats, seems to protect us better, reducing our risk of heart and vascular problems. The greater the decrease in saturated fat, and the more serum total cholesterol is reduced, the greater the protection. People who are currently healthy appear to benefit as much as those at increased risk of heart disease or stroke (people with high blood pressure, high serum cholesterol or diabetes, for example), and people who have already had heart disease or stroke. There was no clear difference in effect between men and women. There is a large body of evidence, including almost 60,000 people who have been in studies assessing effects of reducing saturated fat for at least two years each. Together the studies provide moderate-quality evidence that reducing saturated fat and replacing it with polyunsaturated fats reduces our risk of cardiovascular disease.
This review identified eight randomised controlled trials involving 343 participants, evaluating the benefits of behavioural and cognitive-behavioural therapy. The results show that, compared to a wait-list or pill placebo, BT/CBT is an effective treatment for reducing OCD symptoms and lowering the risk of having OCD after treatment. Based on three studies that directly compared BT/CBT with medication, there was no current evidence to suggest that either BT/CBT or medication was superior to the other. When combined with medication, BT/CBT produces better outcomes than medication alone. Although based on a small number of studies, these findings provide support for the value of BT/CBT in the treatment of children and adolescents with OCD.
This review of trials identified just one trial including 234 patients with early glottic cancer, which compared radiotherapy to open surgery. This was a multicentre randomised controlled trial undertaken in the former Soviet Union, Hungary and Czechoslovakia. Patients were followed up for five years and recurrence-free and survival rates were measured. The results of this trial showed that there was no significant difference in survival between patients treated with radiotherapy or open surgery. Further data from trials comparing radiotherapy and endolaryngeal surgery are needed to determine the best way of treating early laryngeal cancer, however a number of studies have been abandoned because of difficulties in recruiting participants. One trial is still ongoing. We found that there is not enough evidence to show which form of treatment might be better for people with early-stage larynx cancer. The included study is of low quality. The evidence in this review is up to date to September 2014.
Ten studies were found, including 366 patients in total. Most of the studies were performed in intensive care departments but involved only small numbers of patients. In most studies it would be possible for the doctors performing the CTA test to already know the results of the clinical test. This might affect the study results, however this situation would also be the case in normal medical practice. Methods used to report the CTA study also varied from study to study and so the published results were re-analysed to take this into account. When compared to clinical testing for brain death, the CTA test had a sensitivity of 0.85. This means that in 100 cases of patients satisfying the clinical tests for death, the CTA test will correctly identify 85 of the cases. The data also showed that this might be as few as 77 cases per 100 and as many as 91 cases per 100. Our review was unable to tell us how many patients the CTA might falsely give a diagnosis of death for, when the patient was not dead. Based on these results, it appears that CTA is not good enough to be a compulsory test.
Authors of the review identified five controlled trials with a total of 1292 participants who needed immediate care for reduced blood flow in the leg(s) (current until 7 May 2018). Participants were randomly assigned to one of two groups for initial treatment: (1) non-surgical thrombolysis, or (2) surgery. The specific agents used to break up clots (thrombolytic agents) were called recombinant tissue plasminogen activator and urokinase. The included studies provided no clear evidence about which treatment - thrombolysis or surgery - was a better option for preventing limb amputation (limb salvage) and no clear evidence about which treatment was better for preventing death or improving amputation rates within one month, six months, or one year after initial treatment. Evidence for these three outcomes at one month was rated between low and very low quality. No conclusion can be made about which treatment was better for keeping vessels unblocked after treatment (vessel patency) because this outcome was not well reported. More major complications, including bleeding (haemorrhage) and continued ischaemia or blockage (distal embolisation), were reported in the group receiving thrombolysis. There was no difference in the occurrence of stroke at one month between the two treatment groups. Although people receiving initial thrombolysis had increased risk of some complications, they showed greater reduction in the level of intervention required compared with that predicted before intervention. The higher risks of complications with thrombolysis have to be weighted against individual risks in surgery. The quality of the evidence was generally low. We downgraded the quality owing to risk of bias. Bias is a way to describe how researchers, clinicians, or participants might influence results unintentionally. Blinding is a method used to prevent people involved in the trial from knowing what treatment group a participant was in and reducing measurement bias. None of the studies included in this review used methods to stop participants or researchers or outcome assessors from knowing what treatment they were assigned to. Also, there was uncertainty about the true effect of each treatment type. Results show wide differences in outcome measures (effects) between studies (heterogeneity). For example, following surgical treatment, one-year mortality ranged from 9.8% to 42%. Such a wide range in percentages may indicate that the studies compared were quite different. In addition, both selection criteria (duration of treatment and severity of ischaemia) and method of thrombolysis (agent, dose, and duration) varied between studies, making comparison more difficult. This review found no evidence of a difference between thrombolysis and surgery for treatment of acute limb ischaemia for our outcomes of interest. Those receiving thrombolysis treatment may be at higher risk of complications such as bleeding. The quality of data generated by the included studies is low.
Five trials (619 participants) met the inclusion criteria; two addressed inpatient rehabilitation (261 participants) and three (358 participants) home-based settings. There were no trials addressing outpatient centre-based programmes. Pooling of data was not possible due to differences in study design and outcomes used. Methodological assessment showed all trials were of low quality. For inpatient settings early commencement of rehabilitation and clinical pathways led to more rapid attainment of functional milestones (disability) (Functional Independence Measure (FIM) transfer WMD 0.5, 95% CI 0.15, 0.85, number needed to treat to benefit (NNTB) = 6, FIM ambulation WMD 1.55 (95%CI 0.96, 2.14), NNTB = 3), shorter hospital stay, fewer post-operative complications and reduced costs in the first three to four months. Home-based multidisciplinary care improved functional gain (Oxford Hip Score (OHS) WMD at 6 months -7.00 (95%CI -10.36, -3.64), NNT = 2 and quality of life (QoL) and reduced hospital stay in the medium term (six months). No trials addressed longer-term outcomes following hip replacement only. Based on the heterogeneity and the low quality of the included trials that precluded pooled meta-analysis, there is silver level evidence that following hip or knee joint replacement, early multidisciplinary rehabilitation can improve outcomes at the level of activity and participation. The optimal intensity, frequency and effects of rehabilitation over a longer period and associated social costs need further study. Future research should focus on improving methodological and scientific rigour of clinical trials, and use of standardised outcome measures, so that results can be pooled for statistical analysis.
The evidence is current to August 2012. The review included 32 studies and 2762 people with LBP. Most studies included a similar population of people with LBP with and without sciatica. The majority of studies included people with acute, subacute and chronic LBP. Most studies reported follow-up of one to 16 weeks, and a limited number of studies reported long-term follow-up of six months to one year. The included studies show that traction as a single treatment or in combination with physiotherapy is no more effective in treating LBP than sham (pretend) treatment, physiotherapy without traction or other treatment methods including exercise, laser, ultrasound and corsets. These conclusions are valid for people with and without sciatica. There was no difference regarding the type of traction (manual or mechanical). Side effects were reported in seven of the 32 studies and included increased pain, aggravation of neurological signs and subsequent surgery. Four studies reported that there were no side effects. The remaining studies did not mention side effects. The quality of the evidence ranged from very low to moderate. There was a scarcity of high-quality studies, especially those that distinguished between people with different symptom patterns (with and without sciatica, with pain of different duration).
A systematic review summarises evidence from multiple studies to answer a specific research question (e.g. what are the benefits and harms of a particular intervention for a particular health condition?). Often, there are many outcomes that systematic review authors could report to address their research question (e.g. pain, disability and quality of life for patients with musculoskeletal conditions) and many different results available for a particular outcome (e.g. a study might measure pain using three different scales at four time points). If the decision about which outcomes to investigate in a systematic review is made based on the results for those outcomes in the eligible studies, this may lead to bias. While, if the decision about which outcomes to report in a systematic review and the ways to report them is based on the results, this may mislead users of the systematic review. This methodology review summarises the findings of studies examining the inclusion of results and reporting of outcomes in systematic reviews. We searched for studies indexed in electronic bibliographic databases up to May 2013. We included seven studies and found that outcomes investigated and reported in systematic reviews were often changed between the protocol and published systematic review. We also found that it was unclear whether the decision to make these changes was related to how statistically convincing the treatment effect for that outcome was. More studies are needed to confirm if this relationship exists. Also, one study found that some systematic reviews did not report all of the most important outcomes in the abstract of the review. Another study found that outcomes with a more statistically convincing result were more likely to be completely reported in the abstract than other outcomes. The studies that we included were limited to systematic reviews published before 2009. New studies are needed to examine the inclusion of results and reporting of outcomes in more recent systematic reviews.
This review tried to find out which nursing handover style works best. In March 2013 the review authors conducted a wide search for suitable relevant studies (randomised controlled studies) that compared different styles of nursing handover. However, they were not able to identify any randomised controlled studies that investigated the question, and so could draw no conclusions. Further research in this area is urgently needed.
We included 31 studies conducted in Africa, Asia, and Latin America. Participants were skilled birth attendants including doctors, midwives, nurses, auxiliary nurses and their managers. Our synthesis pointed to several factors that affected skilled birth attendants’ provision of quality care. The following factors are based on evidence assessed as of moderate to high confidence. Skilled birth attendants reported that they sometimes had insufficient training during their education or after they had begun work. Where facilities lacked staff, skilled birth attendants’ workloads could increase, it could become difficult to provide supervision, and mothers could receive poorer care. In addition, skilled birth attendants did not always believe that their salaries and benefits reflected their tasks and responsibilities and the personal risks they undertook. Together with poor living and working conditions, these issues could lead to stress and affect skilled birth attendants' family life. Some skilled birth attendants felt that managers lacked capacity and skills, and they felt unsupported when their workplace concerns were not addressed. Possible causes of staff shortages included problems with hiring and assigning health workers to health facilities; lack of funding; poor management and bureaucratic systems; and low salaries. Skilled birth attendants and their managers suggested factors that could help recruit, keep, and motivate health workers, and improve the quality of their work; these included good-quality housing, allowances for extra work, paid vacations, continued education, proper assessments of their work, and rewards. Skilled birth attendants’ ability to provide quality care was also limited by a lack of equipment, drugs, and supplies; blood and the infrastructure to manage blood transfusions; electricity and water supplies; and adequate space and amenities on maternity wards. These factors were seen to reduce skilled birth attendants’ morale, increase their workload and infection risk, and make them less efficient in their work. A lack of transport sometimes made it difficult for skilled birth attendants to refer women to higher levels of care. In addition, women’s negative perceptions of the health system could make them reluctant to accept referral. We identified some other factors that also may have affected the quality of care, which were based on findings assessed as of low or very low confidence. Poor teamwork and lack of trust and collaboration between health workers appeared to negatively influence care. In contrast, good collaboration and teamwork appeared to increase skilled birth attendants’ motivation, their decision-making abilities, and the quality of care. Skilled birth attendants’ workloads and staff shortages influenced their interactions with mothers. In addition, poor communication undermined trust between skilled birth attendants and mothers. We searched for studies published before November 2016.
We included 5 randomised trials with 662 participants out of 93 publications identified through the literature searches. The number of deaths was 47 in the wait-and-see group (334 patients) compared with 26 in the prophylactic cholecystectomy group (328 patients). This review of randomised clinical trials suggests that early removal of the gallbladder decreases the risk of death or of complications from gallstones. The number of patients (662) reviewed in this report prevents some of the subgroup analyses from being conclusive. Further clinical trials, particularly of high-risk patients, would solve this problem.
One study reported a statistically significant reduction in the average anxiety during the waiting period for women who had had a rapid test, but the other found no difference between the two groups. There was also no evidence to support the view that issuing amniocentesis results as soon as they are available is more user friendly than informing women on a pre-defined fixed date. The results remain inconclusive and, therefore, for the time being the choice of communication strategies should be influenced by clinical arguments and cost-effectiveness rather than impact on anxiety. Studies evaluating the effect of different strategies for disclosing results on women anxiety for chorionic villous sampling are needed.
We included 10 randomized controlled trials (RCTs) enrolling 1850 participants in this updated review. One large trial was stopped early because of increased deaths among participants who were randomized to HFO. Four trials reported at least some funding from manufacturers of HFO ventilators. HFO did not reduce the risk of death in hospital in eight trials enrolling 1779 participants. The ability of the lungs to oxygenate blood, measured at 24 to 72 hours of ventilation after randomization, was 18% to 26% better in participants receiving HFO. HFO had no effect on the length of time an artificial breathing machine was required. The risk of unwanted side effects, including low blood pressure or further injury to the lung due to high airway pressure, was not increased. We found substantial inconsistency among clinical trials which reported the effect of HFO on the risk of death in participants with ARDS. The quality of evidence is very low for outcomes that would be most important to patients. This is because of a lack of precision and consistency, and because in many cases the methods used by investigators during clinical trials were not of the highest standard. This indicates that there is considerable uncertainty regarding the effect of HFO on death. Additional randomized trials could change these findings.
We searched for randomised controlled trials in patients of any age with nosebleed requiring intervention. Patients were treated with tranexamic acid (in addition to usual care) compared to placebo, no treatment or any other agent used to stop bleeding. We found six studies that met our inclusion criteria, with a total of 692 participants. Two studies used oral administration of tranexamic acid and four used topical administration. All participants in the studies were adults. Three of the six studies were conducted over 20 years ago. Three studies measured re-bleeding within 10 days. When we combined the results we found that fewer patients who were given either oral or topical tranexamic acid had further episodes of re-bleeding following an initial nosebleed compared to those treated with usual care. The time to stop initial bleeding (control of bleeding within 30 minutes) was measured in four studies. In three studies the proportion of patients whose bleeding stopped within 10 minutes was significantly higher in the group receiving topical tranexamic acid compared to the group receiving a different drug (topical epinephrine and lidocaine or phenylephrine). In the other study there was no significant difference at 30 minutes when topical tranexamic acid was compared with placebo. No studies reported the proportion of patients requiring any further intervention (e.g. repacking, surgery). Only one study of oral tranexamic acid reported the proportion of patients requiring a blood transfusion and there was no evidence of a difference between the groups. Length of hospital stay was reported in two studies. One study reported a significantly shorter stay in the oral tranexamic acid group, while the other found no evidence of a difference. Five studies mention recording "adverse effects". None found any difference between the groups in the occurrence of minor adverse effects (e.g. mild nausea and diarrhoea, 'bad taste' of gel). In one study a patient did develop a superficial thrombophlebitis (inflammation and a blood clot in a vein near the surface of the skin) of both legs following discharge, but the study did not report in which treatment group this happened. No serious adverse event was seen in any of the studies. Overall, the risk of bias in the six studies was low. We graded the quality of the evidence for the main outcome (control of epistaxis: re-bleeding within 10 days) as moderate, which means that further research is likely to have an important impact on our confidence in the estimate of the effect and is likely to change the estimate. In light of this and the fact that 'usual care' has changed, with the development of more modern nasal cauterisation and packing techniques, since three of the included studies were carried out, there remains uncertainty about the role of tranexamic acid in the treatment of patients with epistaxis. Newer research into the effect of tranexamic acid as a treatment for nosebleeds would inform future management decisions for this condition. The evidence in this review is up to date to October 2018.
We found one trial comparing albumin to normal saline; no trials were found comparing albumin to other fluids used to treat hypotension. This trial showed no difference between albumin and normal saline in all outcomes except for the amount of additional saline given, which was less in the group treated with albumin. We concluded that normal saline should be the first choice for treating IDH.
We included three small randomised controlled trials (studies in which participants are assigned to one of two or more treatment groups using a random method) involving a total of 122 children aged up to 12 months who were diagnosed with bronchiolitis. We included one new low-quality trial with 72 children in this update. The three studies were conducted at single centres in France, the UK, and India. All studies compared CPAP with standard therapy. One study was funded by a university hospital; one reported that no funding was received; and one did not mention the funding source. Insufficient evidence was available to permit conclusions about the effect of CPAP on the need for mechanical ventilation in children with bronchiolitis. Limited, low-quality evidence indicated that breathing improved (respiratory rate decreased) in children who received CPAP. The length of time children spent in hospital was similar between the CPAP and the standard therapy groups. No children in the studies were reported to have died. The studies did not report on time to recovery, change in partial oxygen pressure, how often children were admitted to hospital from the emergency department, how long children were in the emergency department, and the need for intensive care admission. There were no local nasal effects, or shock as reported by one study. No children were reported to have had air in the cavity between the lungs and the chest wall, causing lung collapse (pneumothorax) as reported by one study. Two studies did not report about local nasal effects, shock, or pneumothorax. The study added for this update contributed data to the assessment of respiratory rate and need for mechanical ventilation. We found limited, low-quality evidence related to CPAP for children with bronchiolitis. Evidence quality was reduced due to high risk of bias, losses to follow-up, selective reporting, and the wide range of values reported by the included studies.
This was a systematic review of 28 short-term randomised controlled trials of medication augmentation for the treatment of such individuals (740 participants). A significantly larger proportion of patients responded to medication (31.8%) than to placebo (13.6%), (nine trials, 250 participants). Symptom severity was also significantly reduced (14 trials, 337 participants). A substantial proportion of the efficacy evidence base was for the augmentation with antipsychotics of serotonin reuptake inhibitors for obsessive compulsive disorder.
The review includes four studies involving 463 people with venous leg ulcers aged between 42 and 93 years old. The studies compared sulodexide used in combination with local treatment (including wound care and compression therapy) with local treatment alone. The duration of the four studies ranged from one month to three months. Three studies (438 participants) indicated that sulodexide might help to improve ulcer healing, as the proportion of ulcers that were completely healed was increased from 29.8% with local treatment to 49.4% when the participants also received sulodexide. It is unclear whether sulodexide results in more adverse effects (4.4% with sulodexide versus 3.1% without sulodexide). The overall quality of evidence for each outcome varied between low and very low, due to risk of bias, and imprecision (that is, for some outcomes, results from only one, small study were available). This plain language summary is up to date as of 1 July 2015.
This review aims to evaluate evidence on the use of statins at the time of heart surgery to investigate if use can help to prevent kidney failure and how well statins are tolerated among patients. We searched the literature to January 2015 and included seven studies that involved a total of 662 participants to inform our assessment. In these studies, patients planned for heart surgery received statins or placebo (or no treatment at all). Five studies (467 participants) reported rates of kidney failure. We found that there was a high risk of bias in six of the seven included studies. We found no difference in the rate of kidney failure between patients who received statins and those who did not. Two studies (195 patients) reported serum creatinine (a marker of kidney function) after the operation. We found that serum creatinine was lower in patients in the statin group (indicating better kidney function). Other conclusions were limited by the small number of studies. However, patients who received statins did not seem to need less dialysis. They did not have a higher rate of death in hospital and did not have an increased rate of adverse events.
We searched for evidence in March 2017. We found 19 trials involving over 10,000 women. Eighteen of these studies compared the use of Doppler ultrasound of the umbilical artery of the unborn baby with no Doppler or with cardiotocography (CTG, sometimes called electronic fetal monitoring). One more recent trial compared Doppler examination of other fetal blood vessels (ductus venosus) with computerised CTG (short-term variation). Evidence from included studies was assessed as moderate to very low-quality due to incomplete reporting of methods and uncertainty of findings; when the strength of the evidence is low or very low, this means future research may change the results and we cannot be certain about them. Results showed that Doppler ultrasound of the umbilical artery may decrease the number of babies who die, and may lead to fewer caesarean sections and inductions of labour. There was no clear difference in the number of stillbirths, births using forceps or ventouse, or babies with a low Apgar score five minutes after birth. Findings for serious problems in the neonate were not consistent in different studies. In babies with growth restriction, when the decision to deliver was based on late ductus venosus changes or abnormalities on computerised CTG, this appeared to improve long-term (two-year) developmental outcome. Doppler ultrasound in high-risk pregnancies appears to reduce the number of babies who die, and may also lead to fewer obstetric interventions. However, the evidence was of moderate to very low-quality. Further studies of high-quality with long-term follow-up would help us to be more certain.
We found two randomised controlled trials (RCTs) of nonsurgical treatment. One RCT compared three groups of people with mild or moderate UNE (51 people in total). All three groups received written instructions to avoid movements or positions that provoked symptoms. The second group had the same information with elbow splints at night for three months. The third group had the same information with nerve gliding exercises. The other nonsurgical study (55 people) compared a corticosteroid injection with a sham injection. Seven RCTs compared different surgical methods: • simple decompression or transposition of the nerve (submuscular or subcutaneous transposition) (4 trials, 327 participants); • medial epicondylectomy or anterior transposition (1 trial, 47 participants); • anterior subcutaneous transposition or anterior submuscular transposition (1 trial, 48 participants); • keyhole or open surgery (1 trial, 54 participants with 56 trapped nerves). Written information alone was as effective in improving work activities and reducing pain at night as when people also used splints or did exercises. Researchers found no evidence that corticosteroid injection was effective in improving symptoms of UNE. We were able to combine results from three trials comparing two surgical techniques: simple decompression and transposition of the ulnar nerve (subcutaneous or submuscular). We found no important difference in symptom scores between the techniques at 6 to 12 months. Decompression with transposition may result in more deep and superficial wound infections. Trialists found no clinical differences between surgical techniques in the other surgical trials. People undergoing endoscopic surgery were more likely to have a haematoma (an abnormal collection of blood) after surgery. Evidence was insufficient for us to choose the best treatment for UNE. However, we did find that in mild cases, information on movements and positions to avoid may reduce discomfort. Moreover, the combined results from three surgical trials provided moderate-quality evidence that simple decompression surgery and decompression with transposition may be equally effective, but that decompression with transposition may result in more deep and superficial wound infections. The evidence is up to date to 31 May 2016.
Routine prenatal care offers opportunities for healthcare staff to identify women at risk of being abused. In this review we included 10 randomised trials involving a total of 3417 women, seven of which studied pregnant women who were at high risk of partner violence. The interventions examined in the studies included a single brief individualised consultation, case management and referral to a social care worker, and multiple therapy sessions during pregnancy and after birth. Due to the lack of data, and the different way outcomes were reported, we were unable to identify interventions that worked better than others. Studies focused on different outcomes and we were not able to pool information to draw conclusions about the overall effectiveness of the interventions. Most of the studies did not report on whether or not there had been any reduction in episodes of violence. There was evidence from a single study that the total number of women reporting partner violence during pregnancy and after birth was reduced for women receiving a psychological therapy intervention. Several of the studies examined whether women who received interventions were less likely to have depression after the birth of the baby, but the evidence was not consistent. Other outcomes for the baby such as reduced birthweight and preterm birth were reported in only one study, and the intervention did not lessen the risk of preterm birth (< 2500 g). None of the studies reported results for important outcomes such as stillbirth, neonatal death, miscarriage, maternal deaths, antepartum haemorrhage, and placental abruption. More information is needed from well-conducted trials before any particular interventional approach can be recommended.
We reviewed 11 controlled trials with a total of 2514 patients that compared giving MAO-B inhibitors with not giving them in people with early Parkinson's to see if it was safe and effective. The results show that, although MAO-B inhibitors do improve symptoms of Parkinson's and delay the need for levodopa by a few months, they are too weak to have a major effect and do not seem to delay the progression of the condition. They may, however, reduce motor fluctuations although more information is needed to be certain of this. Although they can cause some side-effects, these are generally mild.
This review summarises trials evaluating different measures to prevent leishmaniasis. After searching for relevant trials up to January 2015, we included 14 randomized controlled trials. What is vector and reservoir control and how might they prevent leishmaniasis? Leishmaniasis is a group of infectious diseases caused by Leishmania parasites, which are transmitted between humans and animals by the bite of infected phlebotomine sandflies. There are two main clinical diseases: cutaneous leishmaniasis (CL), where parasites infect the skin, and visceral leishmaniasis (VL), where they infect the internal organs. Leishmaniasis could be prevented by reducing human contact with infected phlebotomine sandflies (the vector), or by reducing the number of infected animals (the reservoir). What the research says? Cutaneous leishmaniasis Using insecticides to reduce the number of sandflies may be effective at reducing the number of new cases of cutaneous leishmaniasis (low quality evidence). However, there is not enough evidence to know whether it is better to use insecticides to spray the internal walls of houses, or use insecticide treated bednets, bedsheets, or curtains. Personal protection using insecticide treated clothing was also evaluated in two small trials in soldiers, but the trials were too small to know whether this was effective (low quality evidence). Visceral leishmaniasis Insecticide treated nets may not be effective at preventing visceral leishmaniasis but this has only been tested in a single trial from India and Nepal (low quality evidence). Although culling dogs is sometimes discussed as a potential way to reduce visceral leishmaniasis, this has not been tested in trials measuring clinical disease.
The review identified 524 potentially relevant articles. Only five randomized controlled trials met our inclusion criteria, and these compared oestrogen with placebo in a total of 305 women who were clinically diagnosed with PMS. We found very low quality evidence to suggest that oral unopposed oestrogen given in the luteal phase of the menstrual cycle is probably ineffective for controlling the symptoms of PMS and may even make them worse. There was very low quality evidence to support the effectiveness of continuous oestrogen (in the form of transdermal patches or subcutaneous implants) plus progestogen, with a small to moderate effect size. A comparison between 200 microgram and 100 microgram doses of continuous oestrogen was inconclusive with regard to effectiveness but suggested that the lower dose was less likely to cause side effects. Uncertainty remains regarding safety, as the identified studies were too small to provide definite answers. Moreover, none of the included trials addressed adverse effects that might occur beyond the typical trial duration of 2 to 8 months. This suggests the choice of oestrogen dose and mode of administration could be based on an individual woman’s preference and modified according to the effectiveness and tolerability of the chosen regimen. The overall quality of the evidence for all comparisons was graded as very low, mainly due to risk of bias in the included studies, imprecision (due to small sample sizes) and differences between the studies.
All six trials were small and had weaknesses that could affect the reliability of their results. We judged the overall quality of the evidence available for each comparison as either low or very low. One trial compared the use of plate fixation with tension band wiring. It found that more people had pain-free elbow motion after plate fixation and fewer people had discomfort from metalwork prominence, which is a well-known problem with wire fixation where the metal wiring on the surface of the bone just under the skin causes pain, discomfort and other problems. Four trials compared different ways of wiring the fracture. Two trials found very little clear evidence of any differences between them. One trial found that adding an intramedullary screw (this is a screw that was inserted through the bone and along the central bone canal) to standard tension band wiring reduced the risk of the metalwork under the skin being prominent. Another trial found that the cable pin system improved function and resulted in fewer complications compared with standard tension band wiring. Finally, one trial compared a new method of fixation using a titanium-nickel device that once implanted takes the shape of the olecranon with locking plate fixation. It found no clear evidence of differences between the techniques in patient-reported function and complications (the only complication was a superficial infection). Currently, there is not enough evidence to determine the best treatment for these fractures with confidence. Further high quality research is needed, which is likely to have an important impact on our confidence in the estimates of the effects and will likely change the estimates.
Our pooled analysis of randomised trials of 4 weeks or more in duration shows that such a reduction in salt intake lowers blood pressure both in individuals with raised blood pressure and in those with normal blood pressure. The fall in blood pressure is shown in both whites and blacks, men and women. Additionally, our results show that a longer-term modest reduction in salt intake has no adverse effect on hormone and lipid levels. These findings provide further strong support for a reduction in population salt intake. This will likely lower population blood pressure and reduce strokes, heart attacks and heart failure. Furthermore, our results are consistent with the fact that the lower the salt intake, the lower the blood pressure. The current recommendations to reduce salt intake to 5-6 grams per day will lower blood pressure, but a further reduction to 3 grams per day will lower blood pressure more. Therefore, 3 grams per day should become the long-term target for population salt intake.
Children and adolescents receiving psychological therapies were less likely to be diagnosed with PTSD and had fewer symptoms of PTSD up to a month after treatment compared with those who received no treatment, treatment as usual or were on a waiting list. Our confidence in these findings is limited as the overall quality of evidence was very low to low. There was no evidence for the effectiveness of psychological therapies beyond one month. There was moderate quality evidence that cognitive-behavioural therapy (CBT) might be more effective in reducing symptoms of PTSD compared to other psychological therapies for up to a month. Adverse effects were not reported. There were no studies which compared psychological therapies to drug treatments. Researchers should conduct high-quality trials to further evaluate the effectiveness of psychological therapies for children and adolescents exposed to trauma. These trials should be designed to ensure that participants and their families are not aware of whether they are receiving psychological therapy, particularly when measures are completed by participants or their parents. In addition, efforts should be made to ensure high rates of follow-up beyond one month after completion of therapy. In addition, studies should compare different types of psychological therapy to give a better indication of whether children and adolescents exposed to different types of trauma are more or less likely to respond to these therapies.
This updated review contains two interrupted-time-series (ITS) studies (studies in which data are collected at multiple time points before and after an intervention), one from the original review, which evaluated a targeted educational intervention aimed at reducing the incidence of wrong-site surgery, and which was found to reduce its incidence. An additional study evaluated the incidence of wrong-site surgery before and after the introduction of the Universal Protocol, however the relevance of these findings regarding the impact of the intervention is unclear given that prior to its introduction, the incidence was decreasing due to other unclear factors. Overall, this review now contains two studies, of relatively low quality evidence, on very specific populations and their generalisability to a larger audience is low.
We found five studies in children that compared an infusion of MgSO4 to a placebo infusion when other treatments had not relieved the attack (usually inhaled bronchodilators, steroids, and sometimes oxygen). These five studies included a total of 182 children. Only three of the studies reported the outcome we were most interested in, which was the need to be admitted to hospital. The studies were published between 1996 and 2000; these were the most current studies we could find when we searched in February 2016. Fewer children who had an infusion of MgSO4 needed to be admitted to hospital compared with placebo. In fact, for every five children treated with the MgSO4, one admission to hospital was prevented. However, the included studies were small, with only 115 children in the main analysis, and the results did vary, so we cannot be absolutely sure of the benefits and harms. As there were so few studies, we also could not tell whether the reduction in hospital admissions was associated with age, severity of the asthma exacerbation, or whether it made a difference what other treatments were given. There were no reports of harm when the children received MgSO4. The review therefore supports the use of MgSO4 in children, however it must be noted that the evidence for its use is very weak.
In October 2015 we searched for as many studies as we could find that were randomised controlled trials and compared the use of an antibiotic or antiseptic with other treatments for pressure ulcers. We found 12 trials involving a total of 576 participants. Most study participants were older people in hospital. Most ulcers were not infected at the start of the trials. The different treatments assessed included povidone iodine, cadexomer iodine, gentian violet, lysozyme, silver dressings, honey, pine resin, silver sulfadiazine, polyhexanide and a combination of nitrofurazone and ethoxy-diaminoacridine. Silver sulfadiazine and nitrofurazone are topical (locally acting) antibiotics while the other treatments are antiseptics. No trials looked at systemic (acting across the whole body) antibiotics. The treatments were compared with each other or to treatments without antimicrobial qualities. Most evidence on wound healing came from trials comparing antiseptics to treatments without antimicrobial qualities. There was no consistent evidence of a benefit to using any particular antimicrobial treatment for pressure ulcers. However, there was some limited evidence that more ulcers healed when treated with some types of alternative dressings without antimicrobial properties than when treated with povidone iodine. All the studies had low numbers of participants, and in some cases these numbers were very small. Many studies did not report important information about how they were carried out so it was difficult to tell whether the results presented were likely to be true. More, better quality, research is needed to determine the effects of antimicrobial treatments on pressure ulcers.
We found three trials set in Jamaica, Nigeria and the UK involving 102 people. In the trials, four different drug treatments (stilboestrol, sildenafil, ephedrine and etilefrine) were compared to placebo. The trials all looked at whether the treatments reduced how often attacks of priapism occurred. There was no difference between any of the treatments compared to placebo. Due to lack of evidence, we are not able to conclude the best treatment of priapism in sickle cell disease. More research is needed. We considered the quality of evidence to be low to very low as all of the trials were at risk of bias and all had low participant numbers.
We identified 10 studies, including six randomised controlled trials (where people are randomly put into one of two or more treatment groups) and four prospective cohort studies (where participants could choose which treatment they received) involving 955 opioid-dependent participants. Four of the studies took place in the UK, three in the USA, two in Italy and one in Australia. Nine of the 10 studies compared treatment with an opioid antagonist (naltrexone or naloxone) plus an adrenergic agonist (clonidine or lofexidine) versus a regimen based on clonidine or lofexidine alone. Other comparisons (placebo, reducing doses of methadone, buprenorphine) made by included studies were too diverse for any meaningful analysis. Four studies received some financial support from a pharmaceutical company. We are uncertain whether peak withdrawal induced by opioid antagonists plus clonidine or lofexidine is more severe than withdrawal managed with clonidine or lofexidine alone, or whether the average severity over the withdrawal period is less, as the certainty of the evidence is very low. Clinicians should warn people of the possibility of delirium in the first day of administration of naltrexone, particularly with higher doses (> 25 mg). People should also know that withdrawal will be moderately severe and that symptoms such as muscle aches, vomiting and diarrhoea, and insomnia are likely to persist despite medication. The studies included in this review were diverse and generally of very low quality. As a result there is considerable uncertainty about the value of approaches using opioid antagonists to induce opioid withdrawal as a means of managing withdrawal from opioid dependence.